Cardiology/Endocrinology - ACCP

Answers to PSAP 2013 Book 1 

(Cardiology/Endocrinology) 

Cardiology I 

Acute Decompensated Heart Failure 

Questions 1–3 pertain to the following case. 

H.M. is a 57-year-old woman with ischemic cardiomyopathy 

(ejection fraction [EF] 30%) who presents to the 

emergency department with dyspnea, and fatigue. Her vital 

signs include blood pressure (BP) 90/75 mm Hg, heart rate 

92 beats/minute, respiratory rate 22 breaths/minute, and 

oxygen saturation 95% on 4 L nasal cannula. Physical examination 

reveals a 15-cm jugular venous distention ( JVD), 

crackles bilaterally, regular rhythm and rate (RRR), and 3+ 

pitting edema. Pertinent laboratory values include sodium 

126 mmol/L, potassium 3.9 mmol/L, BUN 50 mg/dL, and 

SCr 2.1 mg/dL (baseline 1.8 mg/dL). H.M.’s drugs include 

lisinopril 20 mg/day, carvedilol 12.5 mg twice daily, furosemide 

40 mg twice daily, and spironolactone 25 mg/day. 

She is adherent to both dietary restrictions and her drugs. 

1. H.M.’s signs and symptoms are most consistent with 

which one of the following? 

A. Low cardiac output (CO) only. 

B. Fluid overload only. 

C. Both fluid overload and low CO. 

D. Neither fluid overload nor low CO. 

1. Answer: C 

The presenting signs and symptoms of ADHF are generally 

classified as symptoms of fluid overload or low cardiac output. 

Pulmonary symptoms (e.g., dyspnea) and signs (e.g., 

wheezing, hypoxemia) are associated with elevated pulmonary 

filling pressures and pulmonary capillary wedge 

pressure (PCWP). Peripheral edema and ascites are the 

most common signs of systemic fluid overload. Signs and 

symptoms of low cardiac output result in end-organ hypoperfusion, 

which can be evidenced by elevated SCr, elevated 

hepatic transaminases, and gut ischemia manifested by nausea, 

vomiting, abdominal pain and early satiety. This patient 

shows signs and symptoms of both fluid overload and low 

cardiac output, as evidenced through her complaints and 

physical examination (Answer C is correct; and Answer A, 

Answer B, and Answer D are incorrect). 

1. Rodgers JE, Lee, CR. Acute decompensated heart failure. In: 

DiPiro JT, Talbert RL, Yee G, et al., eds. Pharmacotherapy: A 

Pathophysiologic Approach, 8th ed. New York: McGraw-Hill, 

2011:173-216. 

2. Joseph SM, Cedars AM, Ewald GA, et al. Acute decompensated 

heart failure. Tex Heart Inst J 2009;36:510-20. 

PubMed Link 

2. Which one of the following is the best predictor of 

H.M.’s risk of in-hospital mortality? 

A. B-type natriuretic peptide (BNP). 

B. BUN. 

C. SCr concentration. 

D. Systolic BP. 

2. Answer: B 

Data from the Acute Decompensated Heart Failure 

National Registry (ADHERE) analyzed 39 variables and 

found the strongest discriminator of in-hospital mortality 

to be an elevated blood urea nitrogen (BUN) of 43 mg/dL 

or higher (Answer B is correct). B-type natriuretic peptide 

(BNP), SCr, and systolic BP can also be used to assess risk; 

however, their association was not as strong as that of BUN 

(Answer A, Answer C, and Answer D are incorrect). 

1. Fonarow GC, Adams KF, Abraham WT, et al. Risk stratification 

for in-hospital mortality in acutely decompensated heart 

failure. JAMA 2005;293:572-80. 

PubMed Link 

2. Adams KF, Fonarow GC, Emerman CL, et al. Characteristics 

and outcomes of patients hospitalized for heart failure in the 

United States: rationale, design, and preliminary observations 

from the first 100,000 cases in the Acute Decompensated 

Heart Failure National Registry (ADHERE). Am Heart J 

2005;149:209-16. 

PubMed Link 

PSAP 2013 • Cardiology/Endocrinology 1 Answers

3. Which one of the following best explains H.M.’s 

decompensation? 

A. Dietary nonadherence. 

B. Kidney insufficiency. 

C. Acute arrhythmia. 

D. Progression of heart failure (HF). 

3. Answer: D 

This patient reports dietary adherence (Answer A is incorrect). 

Although her SCr is elevated, this is not a significant 

increase and is likely an indication that her HF is progressing 

(Answer B is incorrect). The patient’s ECG shows 

normal sinus rhythm, and she did not have symptoms of 

recent palpitations (Answer C is incorrect). The patient 

does exhibit hyponatremia, which is suggestive of worsening 

HF (Answer D is correct). 

1. McMurray JJ, Adamopoulos S, Anker SD, et al. European 

Society of Cardiology guidelines for the diagnosis and 

treatment of acute and chronic heart failure. Eur Heart J 

2012;33:1787-847. 

PubMed Link 

2. Lindenfeld J, Albert NM, Boehmer JP, et al. Heart Failure 

Society of America 2010 comprehensive heart failure practice 

guidelines. J Card Fail 2010;16:e1-e194. 

PubMed Link 


K.T. is a 78-year-old man with nonischemic cardiomyopathy 

(EF 25%–30%) who presents to the emergency 

department with an acute HF exacerbation. His vital signs 

include BP 135/85 mm Hg, heart rate 98 beats/minute, 

respiratory rate 24 breaths/minute, and oxygen saturation 

96% on 3 L nasal cannula. Physical examination reveals a 

14-cm JVD, RRR, crackles bilaterally, and 3+ bilateral lower 

extremity edema. K.T. has gained 20 lb in the past 3 weeks; 

he reports strict adherence to both dietary restrictions and 

medications. He admits smoking 4 or 5 cigarettes per day. 

He states his β-blocker dose was increased last month to 

obtain better rate control. In the emergency department, 

he has already received furosemide 40 mg intravenously x 

1 with minimal response in urine output. Pertinent laboratory 

values include potassium 4.2 mmol/L, BUN 38 mg/ 

dL, and SCr 1.5 mg/dL (baseline 1.2 mg/dL). Cardiac 

enzymes are within normal limits x 2 sets, and electrocardiography 

shows normal sinus rhythm. K.T.’s drugs include 

lisinopril 40 mg once daily, metoprolol XL 100 mg once 

daily, and furosemide 40 mg twice daily. 

4. Given the predicted BNP result, which one of the following 

best describes K.T.’s condition? 

A. Significant volume overload and ventricular wall 

stretch. 

B. Active myocardial ischemia. 

C. Shortness of breath caused by a noncardiac 

etiology. 

D. Kidney insufficiency. 

4. Answer: A 

B-type natriuretic peptide (BNP) is released and elevated 

in the setting of significant volume overload, causing stretch 

of the ventricular wall. This patient likely has elevated BNP 

because he demonstrates multiple signs and symptoms 

of volume overload and ventricular stretch (Answer A is 

correct). Common laboratory values for assessing active 

myocardial ischemia include creatinine kinase, creatinine 

kinase-myocardial fraction, and troponin, all of which are 

within normal limits (Answer B is incorrect). The BNP may 

be used to rule out other etiologies of shortness of breath 

due to a noncardiac etiology. However, Answer C is incorrect 

because the BNP concentration will be normal in this 

situation. Although BNP may be altered in the setting of 

renal insufficiency, it is not to the same degree as the concentration 

of elevations, which occurs in the setting of fluid 

overload (Answer D is incorrect). 

1. Januzzi JL, Camargo CA, Anwaruddin S, et al. The N-terminal 

pro-BNP investigation of dyspnea in the emergency department 

(PRIDE) study. Am J Cardiol 2005;95:948-54. 

PubMed Link 

2. Weintraub NL, Collins SP, Pang PS, et al. Acute heart failure syndromes: 

emergency department presentation, treatment, and 

disposition: current approaches and future aims. Circulation 

2010;122:1975-96. 

PubMed Link 

5. Which one of the following would be best to recommend 

regarding K.T.’s metoprolol XL dosage? 

A. Continue with no changes. 

B. Increase to 150 mg once daily. 

C. Decrease to 50 mg once daily. 

D. Discontinue. 

5. Answer: C 

The patient experienced fluid accumulation in association 

with recent up-titration of his β-blocker dose; therefore, 

continuation of this same dose, metoprolol XL 100 mg 

once daily, is inappropriate (Answer A is incorrect). An 

increase to metoprolol XL 150mg once daily would only 

be warranted if the patient was tolerating the current dose 

with no fluid accumulation or worsening HF (Answer B is 

incorrect). A decrease to metoprolol XL 50 mg once daily, 

the previously tolerated dose, would be indicated in this situation 

(Answer C is correct). The decision to discontinue 

metoprolol XL should rarely occur and only in the setting of 

cardiogenic shock (Answer D is incorrect). 

1. Jondeau G, Neuder Y, Eicher JC, et al. B-CONVINCED: beta 

blocker continuation versus interruption in patients with 

Answers 

2 

PSAP 2013 • Cardiology/Endocrinology

congestive heart failure hospitalized for a decompensation episode. 

Eur Heart J 2009;30:2186-92. 

PubMed Link 

2. Rodgers JE, Lee, CR. Acute decompensated heart failure. In: 

DiPiro JT, Talbert RL, Yee G, et al., eds. Pharmacotherapy: A 

Pathophysiologic Approach, 8th ed. New York: McGraw-Hill, 

2011:173-216. 

6. Which one of the following interventions is likely to 

have the greatest clinical impact for K.T.? 

A. Education regarding weight monitoring. 

B. Dietary counseling. 

C. Follow-up telephone monitoring after discharge. 

D. Smoking cessation counseling. 

6. Answer: A 

Follow-up telephone monitoring, smoking cessation, 

and dietary counseling are all important interventions. 

However, only daily weight monitoring has been shown to 

decrease hospitalizations significantly and should always 

be emphasized in patient education (Answer A is correct; 

Answer B, Answer C, and Answer D are incorrect). 

1. Weintraub NL, Collins SP, Pang PS, et al. Acute heart 

failure syndromes: emergency department presentation, treatment, 

and disposition: current approaches and future aims. 

Circulation 2010;122:1975-96. 

PubMed Link 




PubMed Link 

C. Initiate clopidogrel 75 mg/day. 

D. Discontinue spironolactone. 

7. Answer: A 

It would be inappropriate to empirically discontinue any 

HF medication that has been associated with a decrease in 

mortality in patients with HF. There is no indication that 

this patient is intolerant of either hydralazine/nitrates or 

spironolactone (Answer B and Answer D are incorrect). 

Aspirin therapy is indicated in all patients receiving LVADs 

to reduce thromboembolic events and pump thrombosis 

(Answer A is correct). The Boyle, et al. study did show a 

low incidence of thromboembolic events in patients treated 

with aspirin and low-intensity warfarin. However, it is 

unknown whether the addition of clopidogrel would result 

in a further reduction of events (Answer C is incorrect). 

1. Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management 

of continuous-flow left ventricular assist devices in advanced 

heart failure. J Heart Lung Transplant 2010;29:S1-S39. 

PubMed Link 

2. Boyle AJ, Russell SD, Teuteberg JJ, et al. Low thromboembolism 

and pump thrombosis with the HeartMate II left 

ventricular assist device: analysis of outpatient anticoagulation. 

J Heart Lung Transplant 2009;28:881-7. 

PubMed Link 

3. Uriel N, Pak SW, Jorde UP, et al. Acquired von willebrand 

syndrome after continuous-flow mechanical device support 

contributes to a high prevalence of bleeding during long-term 

support and at the time of transplantation. J Am Coll Cardiol 

2010;56:1207-13. 

PubMed Link 


M.M. is a 65-year-old African American man with a history 

of ischemic cardiomyopathy (EF 10%) who is admitted for 

left ventricular assist device (LVAD) evaluation. He reports 

that he is “always tired lately” and that he is no longer able 

to complete his activities of daily living without resting. 

Pertinent medical history includes atrial fibrillation, hypertension, 

and stroke. Current drugs include warfarin 3 mg/ 

day, enalapril 10 mg twice daily, metoprolol succinate 100 

mg/day, spironolactone 25 mg/day, hydralazine 25 mg 

twice daily, and isosorbide dinitrate 20 mg twice daily. 

Vital signs include BP 100/70 mm Hg, heart rate 70 beats/ 

minute, respiratory rate 20 breaths/minute, and oxygen saturation 

96% on 2 L nasal cannula. M.M. is approved for 

LVAD, and he is successfully implanted with a HeartMate 

II device. 

7. Which one of the following therapy changes would be 

best before M.M’s discharge? 

A. Initiate aspirin 81 mg/day. 

B. Discontinue hydralazine and isosorbide dinitrate. 

8. Which one of the following is the best choice for managing 

M.M’s warfarin therapy? 

A. Continue therapy for INR goal 1.5–2.5. 

B. Continue therapy with INR goal 2–3. 

C. Continue therapy with INR goal 2.5–3.5. 

D. Discontinue therapy. 

8. Answer: B 

All patients with LVADs should receive anticoagulation 

to prevent pump thrombosis and thromboembolic events 

(Answer D is incorrect). Early anticoagulation therapy with 

LVADs was quite aggressive, with higher INR goals; however, 

recent data indicate that a lower target range of 1.5-2.5 

results in a low incidence of thromboembolism and also 

minimizes bleeding. However, patients with a separate indication 

for anticoagulation – such as atrial fibrillation with a 

CHADS 2 

score of 4, as is the case with this patient – warrant 

traditional INR goals of 2–3 (Answer B is correct). An INR 

goal of 1.5–2.5 may not provide adequate stroke prevention 

in the face of concomitant atrial fibrillation (Answer A is 

incorrect). An INR goal of 2.5–3.5 could increase the risk 

of bleeding (Answer C is incorrect). 


1. Boyle AJ, Russell SD, Teuteberg JJ, et al. Low thromboembolism 

and pump thrombosis with the HeartMate II left 

ventricular assist device: analysis of outpatient anticoagulation. 

J Heart Lung Transplant 2009;28:881-7. 

PubMed Link 

2. John R, Kamdar F, Liao K, et al. Low thromboembolic risk for 

patients with the HeartMate II left ventricular assist device. J 

Thorac Cardiovasc Surg 2008;136:1318-23. 

PubMed Link 




PubMed Link 

9. Three months later, M.M. presents to the emergency 

department with dizziness, fever, chills, and general 

malaise. Which one of the following is best to recommend 

for M.M.? 

A. Begin antibiotic therapy targeted at gram-positive 

organisms. 

B. Begin broad-spectrum antibiotic therapy and 

admit for monitoring. 

C. Be closely monitored and initiate antibiotic 

therapy only if cultures are positive. 

D. Begin broad-spectrum antibiotic therapy and 

discharge to home. 

9. Answer: B 

Most LVAD infections are caused by gram-positive bacteria; 

however, gram-negative bacteria need to be considered 

(Answer A is incorrect). Because the consequences of infection 

can be devastating in this population, it is recommended 

that patients be admitted and treated with intravenous antibiotic 

therapy (Answer B is correct). Answer C and Answer 

D are incorrect in that they do not warrant the patient to be 

admitted to the hospital for close monitoring. 




PubMed Link 

2. Topkara VK, Kondareddy S, Malik F, et al. Infectious complications 

in patients with left ventricular assist device: etiology 

and outcomes in the continous-flow era. Ann Thorac Surg 

2010;90:1270-7. 

PubMed Link 


T.A. is 76-year-old man who presents to the hospital with 

an acute HF exacerbation. He experiences dyspnea on 

exertion, 4-pillow orthopnea, and a 15-lb weight gain over 

3 weeks. Physical examination reveals JVD to the angle 

of the jaw, positive S3 heart sound, bilateral rales on auscultation, 

and 3+ bilateral lower extremity edema to the 

thighs. Chest radiography reveals pulmonary edema and 

pleural effusions. T.A.’s medical history is significant for 

non–ST-elevation myocardial infarction with four-vessel 

coronary artery bypass grafting 15 years ago, type 2 diabetes 

mellitus, and permanent atrial fibrillation. Vital signs 

include BP 119/72 mm Hg, heart rate 82 beats/minute, 


92%. Electrocardiography reveals several episodes of 

nonsustained ventricular tachycardia in the emergency 

department. His LVEF 1 month ago was 25%. Laboratory 

values include sodium 128 mEq/L, potassium 4.1 mEq/L, 

chloride 100 mEq/L, carbon dioxide 25 mEq/L, BUN 34 

mg/dL (baseline 24 mg/dL), and SCr 1.3 mg/dL (baseline 

SCr 0.9 mg/dL). Drugs on admission include lisinopril 20 

mg/day, carvedilol 12.5 mg twice daily, bumetanide 1 mg 

twice daily, hydralazine 50 mg three times/day, isosorbide 

dinitrate 20 mg three times/day, aspirin 81 mg/day, warfarin 

5 mg/day, and insulin glargine 35 units at bedtime. 

10. Which one of the following is the best initial diuretic 

therapy for T.A.? 

A. Bumetanide 1 mg intravenously. 

B. Bumetanide 2 mg intravenously. 

C. Metolazone 10 mg orally. 

D. Nesiritide 0.02 mcg/kg/minute intravenous 

continuous infusion. 

10. Answer: B 

On the basis of the signs and symptoms described, this 

patient has acute HF with fluid overload. For patients on 

a loop diuretic at home, initial management should consist 

of doubling the home dose and intravenous administration 

(Answer B is correct). It is essential to consider the absorption 

properties of loop diuretics to determine appropriate 

conversion from oral to intravenous therapy. Bumetanide 

has approximately 90% bioavailability, so the oral dose 

must be doubled to provide twice the home dose (Answer 

A is incorrect). Metolazone could be considered, but the 

dose listed is excessive, and this agent may cause severe 

electrolyte abnormalities in a patient with episodes of nonsustained 

VT (Answer C is incorrect). Nesiritide could be 

considered for symptomatic improvement in addition to 

intravenous loop diuretic, but this agent provides no mortality 

benefits or reductions in length of stay (Answer D is 

incorrect). 




PubMed Link 

2. Felker GM. Diuretic management in heart failure. Congest 

Heart Fail 2010;16(suppl 1):S68-S72. 

PubMed Link 

Answers 

4 


11. Which one of the following would be best for rapidly 

improving T.A.’s symptoms? 

A. Tolvaptan 30 mg orally once daily. 

B. Chlorothiazide 500 mg intravenously once daily. 

C. Nitroprusside 4 mcg/kg/minute intravenous 


D. Nitroglycerin 30 mcg/minute intravenous 


11. Answer: D 

This patient is experiencing symptomatic ADHF characterized 

by dyspnea on exertion, orthopnea, low oxygen 

saturation, and tachypnea. Vasodilators are indicated for 

rapid symptomatic relief. The patient’s blood pressure will 

tolerate a vasodilator; therefore, nitroglycerin is the best 

choice (Answer D is correct). Nitroprusside is a reasonable 

option, but the dose of 4 mcg/kg/minute is an overly 

aggressive dose (Answer C is incorrect). This patient has not 

been proved to be diuretic resistant; therefore, appropriate 

loop diuretic dosing should produce a symptom response. 

The patient’s sodium is also low, and this can be further 

exacerbated by sequential nephron blockade (Answer B is 

incorrect). Tolvaptan has been shown to improve symptoms 

in ADHF but not as rapidly as intravenous vasodilators, and 

AVP antagonists are not recommended in guidelines. The 

description of this patient does not suggest symptomatic 

hyponatremia (Answer A is incorrect). 

1. Elkayam U, Tasissa G, Binanay C, et al. Use and impact of inotropes 

and vasodilator therapy in hospitalized patients with 

severe heart failure. Am Heart J 2007;153:98-104. 

PubMed Link 

2. Konstam MA, Gheorghiade M, Burnett JC, et al. Effects of oral 

tolvaptan in patients hospitalized for worsening heart failure: 

the EVEREST Outcome Trial. JAMA 2007;297:1319-31. 

PubMed Link 

3. Peacock WF, Fonarow GC, Emerman CL, et al. Impact of early 

initiation of intravenous therapy for acute decompensated heart 

failure on outcomes in ADHERE. Cardiology 2007;107:44-51. 

PubMed Link 

4. Peacock WF, Emerman C, Costanzo MR, et al. Early vasoactive 

drugs improve heart failure outcomes. Congest Heart Fail 

2009;15:256-64. 

PubMed Link 

5. Stough WG, O’Connor CM, Gheorghiade M. Overview of current 

noninodilator therapies for acute heart failure syndromes. 

Am J Cardiol 2005;96[suppl]:41G–6G). 

PubMed Link 

12. Three hours after initiation of therapy and monitoring, 

T.A. has produced 200 mL of urine. He says his dyspnea 

has not improved. His current vital signs include 

BP 110/70 mm Hg, heart rate 79 beats/minute, 


93%. Which one of the following would be best to 

recommend for T.A.? 

A. Increase to bumetanide 4 mg intravenously. 

B. Initiate ultrafiltration. 

C. Initiate milrinone 0.375 mcg/kg/minute. 

D. Continue the current regimen because symptoms 

have improved. 

12. Answer: A 

Patients without kidney dysfunction should respond by 

producing at least 500 mL of urine 2 hours after administration. 

If this end point is not achieved, clinicians should 

consider options for more aggressive volume removal. 

Because this patient was taking bumetanide 1 mg twice 

daily at home and was given bumetanide 2 mg intravenously 

initially, his dose should be increased to bumetanide 

4 mg intravenous at this time (Answer A is correct). 

Ultrafiltration is a reasonable option; however, this patient 

has not yet failed diuretics, so it is too soon for this costly 

intervention (Answer B is incorrect). Milrinone should not 

be added because the patient has an adequate blood pressure 

and is not showing signs of low CO. He also has runs of 

nonsustained ventricular tachycardia, which may be exacerbated 

by inotropes (Answer C is incorrect). Continuing the 

current regimen is inappropriate because this patient had 

several signs and symptoms of fluid overload on admission 

and did not respond adequately to the initial bumetanide 

dose (Answer D is incorrect). 

1. Abraham WT, Adams KF, Fonarow GC, et al. In-hospital 

mortality in patients with acute decompensated heart failure 

requiring intravenous vasoactive medications: an analysis 

from the acute decompensated heart failure national registry 

(ADHERE). J Am Coll Cardiol 2005;46:57-64. 

PubMed Link 

2. Cuffe MS, Califf RM, Adams KF, et al. Short-term intravenous 

milrinone for acute exacerbation of chronic heart failure: a randomized 

controlled trial. JAMA 2002;287:1541-7. 

PubMed Link 

3. DiDomenico RJ, Park HY, Southworth MR, et al. Guidelines 

for acute decompensated heart failure treatment. Ann 

Pharmacother 2004;38:649-60. 

PubMed Link 

4. Felker GM. Diuretic management in heart failure. Congest 

Heart Fail 2010;16(suppl 1):S68-S72. 

PubMed Link 

Questions 13 and 14 pertain to the following case. 

A.L. is a 73-year-old woman who presents to the emergency 

department with extreme dyspnea on exertion when 

walking from one room to the next at home. She has experienced 

lethargy and gradual reduction in exercise tolerance 

for the past 3 months. A.L. also admits feeling cold most of 


the day. She has been adherent to her dietary restrictions 

and drugs. Her weight has been stable at 85 kg during this 

time. She has a history of alcohol-induced nonischemic 

cardiomyopathy (LVEF 15%). Vital signs on admission 

include BP 82/56 mm Hg (without orthostasis), heart rate 

95 beats/minute, and respiratory rate 18 breaths/minute. 

On physical examination, she shows a stable 6-cm JVD, 

no pulmonary edema, no ascites, and no lower extremity 

edema. Laboratory analysis reveals sodium 135 mmol/L, 

potassium 4.1 mmol/L, carbon dioxide 28 mEq/L, chloride 

99 mEq/L, BUN 42 mg/dL (baseline 34 mg/dL), 

SCr 1.8 mg/dL (baseline 1.4 mg/dL), and magnesium 1.8 

mg/dL. A.L. has been stable on her oral HF drugs, which 

include metoprolol succinate 50 mg once daily, enalapril 5 

mg twice daily, and spironolactone 25 mg once daily. 

13. Which one of the following hemodynamic subsets best 

describes A.L.? 

A. Warm and dry. 

B. Warm and wet. 

C. Cold and dry. 

D. Cold and wet. 

13. Answer: C 

This patient shows signs and symptoms of low CO (i.e., 

lethargy and reduced exercise tolerance) that have progressively 

worsened the past several months. Additionally, her 

vital signs (e.g., BP of 82/56 mm Hg) and laboratory profile 

(e.g., SCr = 1.8 mg/dL) are consistent with this low CO, 

suggesting that she is “cold.” Although the patient has been 

adherent to her diet and drug regimens, she has no symptoms 

of volume overload such as peripheral or pulmonary 

edema that would suggest that she is “wet.” The cold and dry 

hemodynamic subset best describes her current condition 

(Answer C is correct; Answer A, Answer B, and Answer D 

are incorrect). 

1. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update 

incorporated into the ACC/AHA 2005 Guidelines for the 

Diagnosis and Management of Heart Failure in Adults: a report 

of the American College of Cardiology Foundation/American 

Heart Association Task Force on Practice Guidelines: developed 

in collaboration with the International Society for Heart 

and Lung Transplantation. Circulation 2009;119:e391-e479. 

PubMed Link 

2. McMurray JV, Adamopoulos S, Anker SD, et al. European Society 

of Cardiology guidelines for the diagnosis and treatment of acute 

and chronic heart failure. Eur Heart J 2012;33:1787-847. 

PubMed Link 

14. Which one of the following agents would most likely 

benefit A.L. at this time? 

A. Milrinone 0.375 mcg/kg/minute. 

B. Dobutamine 5 mcg/kg/minute. 

C. Nitroglycerin 10 mcg/minute. 

D. Furosemide 40 mg intravenously. 

14. Answer: B 

This patient has progressive worsening of HF leading to 

acute decompensation characterized by a cold and dry 

profile with symptomatic hypotension; therefore, nitroglycerin 

would not be an appropriate option (Answer C is 

incorrect). Because she has no signs or symptoms of being 

“wet,” a loop diuretic would not be an appropriate choice 

because furosemide could deplete her intervascular volume 

(Answer D is incorrect). Her worsening kidney function, 

reduced exercise tolerance, and feeling of being cold is 

likely caused by the reduction in CO; thus she may warrant 

an inotrope. Because of its mechanism of action, milrinone 

has an increased risk of hypotension and its effects 

may be prolonged in patients with kidney dysfunction. This 

patient is already hypotensive and has kidney dysfunction; 

therefore, milrinone would not be an appropriate choice 

(Answer A is incorrect). Dobutamine would be the best 

choice to improve CO and limit the risk of drug-induced 

hypotension despite the patient being on a β-blocker at 

home (Answer B is correct). 

1. Cuffe MS, Califf RM, Adams KF, et al. Short-term intravenous 

milrinone for acute exacerbation of chronic heart failure: a randomized 

controlled trial. JAMA 2002;287:1541-7. 

PubMed Link 




PubMed Link 


C.J. is a 75-year-old man (height 5′8′′, weight 72 kg) with 

ischemic cardiomyopathy (EF 30%) presenting to the cardiovascular 

intensive care unit with acute decompensated 

heart failure (ADHF) and symptoms of worsening dyspnea 

on exertion, orthopnea, and paroxysmal nocturnal 

dyspnea. His medical history includes coronary artery 

disease, hyperlipidemia, hypertension, and chronic kidney 

disease. An implantable cardioverter-defibrillator was 

placed 2 years ago after an episode of ventricular tachycardia, 

but there have been no occurrences since then. His 

vital signs are BP 117/68 mm Hg, heart rate 75 beats/ 

minute, respiratory rate 23 breaths/minute, and oxygen 

saturation 94% on 4 L nasal cannula. He is noted to have 

a JVD up to his ear, rales bilaterally, and 3+ bilateral lower 

extremity edema up to his knees, but only mild abdominal 

edema. He admits a 20-lb weight gain in the past 2 

weeks after running out of his home drugs. Pertinent laboratory 

values include sodium 136 mmol/L, potassium 4.8 

mmol/L, BUN 59 mg/dL, SCr 2.3 mg/dL (baseline 1.7 

mg/dL), N-terminal proBNP 9543 pg/mL, AST 28 U/L, 

Answers 

6 


ALT 32 U/L, and lactate dehydrogenase 125 U/L. C.J.’s 

drugs include atorvastatin 40 mg/day, aspirin 81 mg/day, 

enalapril 10 mg twice daily, carvedilol 12.5 mg twice daily, 

digoxin 125 mcg/day, and furosemide 40 mg twice daily. 

15. Based on current literature, which one of the following 

would be most effective for rapid onset volume removal 

and symptom relief without long-term adverse effects 

in C.J.? 

A. Furosemide 40 mg intravenously every 12 hours. 

B. Furosemide 100 mg intravenously every 12 hours. 

C. Furosemide 4 mg/hour intravenous continuous 

infusion. 

D. Furosemide 8 mg/hour intravenous continuous 

infusion. 

15. Answer: B 

Results from the Diuretics Optimization Strategies 

Evaluation (DOSE) trial, a large, randomized controlled 

study, have helped clinicians better understand the most 

effective intravenous loop diuretic dosing regimen in 

patients with ADHF. In this trial, high-dose loop diuretics 

produced more net fluid loss, weight loss, and relief from 

dyspnea with only temporary worsening of kidney function. 

On the basis of these data, aggressive diuresis with 

furosemide is appropriate for this patient (Answer B is correct) 

rather than conservative dosing to rapidly improve 

dyspnea symptoms (Answer A is incorrect). Continuous 

infusion was found to be no more effective than intravenous 

bolus dosing. Furthermore, an intravenous bolus 

should be administered before starting a continuous infusion 

to achieve more rapid diuresis and improvement in 

symptoms (Answer C and Answer D are incorrect). 

1. DiDomenico RJ, Park HY, Southworth MR, et al. Guidelines 

for acute decompensated heart failure treatment. Ann 

Pharmacother 2004;38:649-60. 

PubMed Link 

2. Peacock WF, Costanzo MR, De Marco T, et al. Impact of intravenous 

diuretics on the outcomes of patients hospitalized with 

acute decompensated heart failure: insights from the ADHERE 

registry. Cardiology 2009;113:12-9. 

PubMed Link 

3. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in 

patients with acute decompensated heart failure. N Engl J Med 

2011;364:797-805. 

PubMed Link 

16. C.J. responds poorly to the initial diuretic dosing, producing 

only 800 mL of urine overnight. Which one of 

the following would be best to recommend for overcoming 

possible diuretic resistance and successfully 

removing excess volume for C.J.? 

A. Metolazone 5 mg by mouth daily. 

B. Chlorothiazide 1000 mg intravenously twice 

daily. 

C. Hydrochlorothiazide 100 mg by mouth daily. 

D. Spironolactone 25 mg by mouth daily. 

16. Answer: A 

After escalating doses of intravenous loop diuretic fail to 

resolve symptoms, sequential nephron blockade is a reasonable 

option and is recommended in guidelines to overcome 

diuretic resistance. Because this patient has chronic kidney 

disease (baseline CrCl about 40 mL/minute) with worsening 

kidney function (current CrCl about 30 mL/minute), 

metolazone is a good option because it is less dependent 

on glomerular filtration to reach the site of action (Answer 

A is correct). The patient has only mild abdominal edema, 

so absorption should not be affected. Chlorothiazide and 

hydrochlorothiazide could be considered, but these may not 

reach the intended site of action because of dependence on 

adequate glomerular filtration. The chlorothiazide and hydrochlorothiazde 

dosing options are also high for a starting dose 

(Answer B and Answer C are incorrect). Spironolactone is 

not a potent diuretic and may be considered for chronic therapy; 

however, this drug is rarely used to augment diuresis in 

ADHF (Answer D is incorrect). 

1. Jentzer JC, DeWald TA, Hernandez AF. Combination loop 

diuretics with thiazide-type diuretics in heart failure. J Am Coll 

Cardiol 2010;56:1527-34. 

PubMed Link 




PubMed Link 

17. Because of C.J.’s poor initial response, a right heart catheterization 

is performed for hemodynamic assessment. 

Key results include central venous pressure 10 mm Hg, 

pulmonary artery systolic/diastolic pressure 44/30 mm 

Hg, pulmonary capillary wedge pressure (PCWP) 29 

mm Hg, CO 3.5 L/minute, cardiac index (CI) 1.9 L/ 

minute/m 2 , systemic vascular resistance (SVR) 2000 

dynes/second/cm -5 , and systemic BP 105/65 mm Hg. 

Which one of the following would be best to recommend 

for hemodynamic improvement and to minimize 

the risk of in-hospital mortality for C.J.? 

A. Dobutamine 5 mcg/kg/minute. 

B. Dopamine 10 mcg/kg/minute. 

C. Nesiritide 2 mcg/kg bolus followed by 0.03 mcg/ 

kg/minute. 

D. Nitroprusside 0.2 mcg/kg/minute. 

17. Answer: D 

This patient is characterized into the cold and wet subset 

on the basis of symptoms and now hemodynamic evidence 


from right heart catheterization. Inotropes have been 

linked to increased in-hospital mortality and ventricular 

arrhythmias; therefore, they should be used only when 

necessary if patients show symptoms of low CO and hypotension 

or for progression to end-stage HF (Answer A and 

Answer B are incorrect). Vasodilators are the preferred 

agents for this patient on the basis of his high PCWP (preload), 

high SVR (afterload), and low CI. Reducing preload 

and afterload to normal values reduces myocardial wall 

stress and optimizes CI. Nesiritide would be an appropriate 

drug selection, but the dosing here is too aggressive 

and may induce hypotension (Answer C is incorrect). 

Nitroprusside is a balanced arterial-venous dilator with 

fast onset and a short half-life. This patient has normal 

liver function and chronic kidney disease, but temporary 

initiation of nitroprusside at low doses is safe and effective, 

making nitroprusside the best choice in this case 

(Answer D is correct). 

1. Abraham WT, Adams KF, Fonarow GC, et al. In-hospital 

mortality in patients with acute decompensated heart failure 

requiring intravenous vasoactive medications: an analysis 

from the acute decompensated heart failure national registry 

(ADHERE). J Am Coll Cardiol 2005;46:57-64. 

PubMed Link 

2. Burger AJ, Horton DP, LeJemtel T, et al. Effect of nesiritide 

(B-type natriuretic peptide) and dobutamine on ventricular 

arrhythmias in the treatment of patients with acutely decompensated 

congestive heart failure: The PRECEDENT study. 

Am Heart J 2002;144:1102-8. 

PubMed Link 




PubMed Link 

4. Mullens W, Abrahams Z, Francis GS, et al. Sodium nitroprusside 

for advanced low-output heart failure. J Am Coll 

Cardiol 2008;52:200-7. 

PubMed Link 

C. Give conivaptan 20 mg intravenous bolus, 

followed by 20 mg administered intravenously 

over 24 hours. 

D. Give tolvaptan 30 mg by mouth daily. 

18. Answer: B 

The only guideline-recommended treatment for asymptomatic 

hyponatremia is fluid restriction. This patient 

has a rather liberal fluid restriction at this point, so further 

restriction is the best option (Answer B is correct). 

Diuretics can deplete electrolytes because the main mechanism 

for fluid removal is driven by the prevention of 

sodium reabsorption in renal tubules (Answer A is incorrect). 

Conivaptan has not been proved to be effective in 

patients with HF (Answer C is incorrect). Tolvaptan 

has FDA label approval for symptomatic hypervolemic 

or euvolemic hyponatremia or for sodium less than 125 

mEq/L. It is also effective for rapid symptom relief for 

patients with ADHF but provides no morbidity or mortality 

benefits (Answer D is incorrect). 

1. Gheorghiade M, Konstam MA, Burnett JC, et al. Shortterm 

clinical effects of tolvaptan, an oral vasopressin 

antagonist, in patients hospitalized for heart failure. JAMA 

2007;297:1332-43. 

PubMed Link 

2. Gheorghiade M, Gattis WA, O’Connor CM, et al. Effects of 

tolvaptan, a vasopressin antagonist, in patients hospitalized 

with worsening heart failure. JAMA 2004;291:1963-71. 

PubMed Link 

3. Konstam MA, Gheorghiade M, Burnett JC, et al. Effects of oral 

tolvaptan in patients hospitalized for worsening heart failure: 

the EVEREST Outcome Trial. JAMA 2007;297:1319-31. 

PubMed Link 




PubMed Link 

18. A 69-year-old man with a history of nonischemic cardiomyopathy 

is admitted to the hospital with severe 

volume overload after running out of his home loop 

diuretic 3 weeks ago. On admission, he was placed 

on a 2-L/day fluid restriction and given intravenous 

furosemide with successful removal of volume. He is 

almost back to his baseline weight but is now hyponatremic 

with a sodium concentration of 124 mmol/L. 

His mental status is at baseline, and he has no nausea, 

vomiting, or headache. Which one of the following is 

best to recommend for this patient’s hyponatremia? 

A. Continue the current plan because further 

volume removal will correct his sodium. 

B. Change his fluid restriction to 1.5 L/day and 

continue to monitor. 

19. A 65-year-old man admitted for progressive HF 

caused by ischemic cardiomyopathy has become 

refractory to most evidence-based medications. He 

has been hospitalized for ADHF six times in the 

past 4 months. Similar to his previous admissions, 

the patient presents with cold and wet symptoms. 

His evaluation for heart transplantation was completed 

during previous admissions. He also has a 

medical history of coronary artery disease, diabetes 

mellitus, hypertension, chronic kidney insufficiency, 

and hypothyroidism. At this admission, the patient 

has diminished urine output to escalating doses of 

a bumetanide intravenous continuous infusion and 

chlorothiazide intravenous bolus every 12 hours. His 

cardiologist would like to perform a right heart catheterization 

to optimize hemodynamics and place 

Answers 

8 


an intra-aortic balloon pump to move him up on the 

transplant list. The patient’s current laboratory values 

include sodium 131 mEq/L, potassium 3.9 mEq/L, 

carbon dioxide 28 mEq/L, chloride 101 mEq/L, 

BUN 55 mg/dL, SCr 2.2 mg/dL, magnesium 2.2 mg/ 

dL, AST 205 U/L, ALT 191 U/L, and total bilirubin 

1.9 mg/dL. The right heart catheterization shows the 

following: central venous pressure 9 mm Hg, pulmonary 

artery systolic/diastolic pressure 52/25 mm Hg, 

PCWP 24 mm Hg, CO 3.1 L/minute, CI 1.6 L/minute/m 

2 , SVR 2040 dynes/second/cm -5 , and systemic 

BP 89/59 mm Hg. With this new information and his 

current clinical status, which one of the following is the 

best vasoactive drug to aid as a bridge to transplant in 

this patient? 

A. Milrinone 0.2 mcg/kg/minute. 

B. Dobutamine 10 mcg/kg/ minute. 

C. Nitroglycerin 10 mcg/minute. 

D. Nitroprusside 6 mcg/kg/ minute. 

19. Answer: A 

This patient was admitted to elevate his status on the transplant 

list. After completion of a right heart catheterization 

for hemodynamic evaluation, he was found to have a high 

preload and afterload with low CI. Milrinone has multiple 

hemodynamic properties, including preload and afterload 

reduction plus augmentation of CO, which makes it a good 

choice for this patient (Answer A is correct). Dobutamine 

also increases CO but would have less effect on PCWP and 

SVR. Dobutamine 10 mcg/kg/minute is also too aggressive 

for a starting dose (Answer B is incorrect). Vasodilators 

are often used as a BTT to minimize myocardial workload. 

Nitroglycerin is good for short-term improvement in symptoms 

and hemodynamics, but it is limited by tachyphylaxis 

when used for prolonged periods (Answer C is incorrect). 

Nitroprusside is not the best choice in patients who may be 

on the transplant list for extended periods and may rapidly 

decompensate, leading to liver and renal insufficiency. Such 

organ dyfuncations can lead to potential cyanide toxicity. 

Additionally, the starting dose of nitroprusside ( 6 mcg/kg/ 

minute) is too aggressive (Answer D is incorrect). 

1. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update 

incorporated into the ACC/AHA 2005 Guidelines for the 

Diagnosis and Management of Heart Failure in Adults: a report 

of the American College of Cardiology Foundation/American 

Heart Association Task Force on Practice Guidelines: developed 

in collaboration with the International Society for Heart 

and Lung Transplantation. Circulation 2009;119:e391-e479. 

PubMed Link 




PubMed Link 

20. The cardiology section at your hospital wants to add 

nesiritide as part of the routine standing order set for 

all patients admitted with ADHF, volume overload, 

and systolic BP greater than 90 mm Hg. Given your 

knowledge as a pharmacist reviewer, which one of the 

following provides the most accurate feedback on the 

safety and efficacy of nesiritide? 

A. Disagree; there are clear data showing increases 

in mortality and kidney dysfunction when used 

routinely. 

B. Disagree; there are no data showing a decrease 

in morbidity, mortality, or hospital readmissions 

to support routine use. 

C. Agree; the aggregate data support nesiritide use 

to decrease length of stay and prevent hospital 

readmissions. 

D. Agree; nesiritide has the benefit of lowering 

loop diuretic requirements, which translates to 

decreases in overall mortality. 

20. Answer: B 

At this time, there are no data to support the routine use of 

nesiritide; it has shown hemodynamic benefits comparable 

with nitroglycerin, but these data have been criticized 

for nitroglycerin underdosing. The ASCEND-HF study 

was not able to show a significant difference in dyspnea 

score or the combined end point of hospital readmissions 

or death (Answer B is correct). Meta-analyses have also 

shown a possible link to kidney dysfunction and mortality 

with nesiritide; however, these analyses have been 

criticized because of the studies selected, and the results 

are hypothesis generating at best (Answer A is incorrect). 

Nesiritide does not decrease LOS, prevent hospital readmissions, 

or lower diuretic requirements (Answer C and 

Answer D are incorrect. 

1. O’Connor CM, Hernandez AF, Armstrong PW, et al. Effect 

of nesiritide in patients with acute decompensated heart failure. 

N Engl J Med 2011;365:32-43. 

PubMed Link 

2. Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk 

of worsening renal function with nesiritide in patients 

with acutely decompensated heart failure. Circulation 

2005;111:1487-91. 

PubMed Link 

3. Sackner-Bernstein JD, Kowalski M, Fox M, et al. Short-term 

risk of death after treatment with nesiritide for decompensated 

heart failure. JAMA 2005;293:1900-5. 

PubMed Link 

4. VAMC Investigators. Intravenous nesiritide versus nitroglycerin 

for treatment of decompensated congestive heart failure. 

JAMA 2002;287:1531-40. 

PubMed Link 


Newer Antithrombotic Agents 

and Their Role in ACS 

21. A 60-year-old woman (weight 85 kg) presents to the 

emergency department with crushing substernal chest 

pain and ST-segment elevations on electrocardiography. 

She has no significant medical history; she is prescribed 

a heparin intravenous infusion and aspirin 325 mg 

orally daily. Laboratory results are hemoglobin 12.0 g/ 

dL, hematocrit 36%, and SCr 1.0 mg/dL. Her physician 

wants the fastest-acting P2Y12 antagonist regimen 

before percutaneous coronary intervention (PCI) and 

asks you for a recommendation. Which one of the following 

regimens is best to recommend for this patient? 

A. Clopidogrel 300 mg loading dose (LD), followed 

by 75 mg/day. 

B. Prasugrel 60 mg LD, followed by 10 mg/day. 

C. Clopidogrel 600 mg LD, followed by 75 mg/day. 

D. Ticagrelor 180 mg LD, followed by 90 mg twice 

daily. 

21. Answer: B 

Both ticagrelor and prasugrel have shown quicker onset of 

action than clopidogrel (Answer A and Answer C are incorrect). 

Answer D is incorrect because the onset for ticagrelor 

is 90 minutes compared with 30 minutes for prasugrel and 

the aspirin dose prescribed. Prasugrel’s onset of action is 

30 minutes, making it the fastest-acting P2Y12 antagonist 

(Answer B is correct). 

1. Jakubowski JA, Matsushima N, Asai F, et al. A multiple dose 

study of prasugrel (CS-747), a novel thienopyridine P2Y12 

inhibitor, compared with clopidogrel in healthy humans.Br J 

Clin Pharmacol 2007;63:421-30. 

PubMed Link 

2. Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind 

assessment of the ONSET and OFFSET of the 

antiplatelet effects of ticagrelor versus clopidogrel in patients 

with stable coronary artery disease: the ONSET/OFFSET 

study. Circulation 2009;120:2577-85. 

PubMed Link 

22. A 76-year-old man (weight 65 kg) presents to the 

emergency department with substernal chest pain, 

ST-segment depressions on electrocardiography, and 

elevated troponins. His medical history is significant for 

hypertension and a previous ischemic stroke. Laboratory 

results are hemoglobin 12.4 g/dL, hematocrit 37%, SCr 

1.2 mg/dL, and troponin 5.0 ng/mL. He is prescribed 

a heparin intravenous infusion and aspirin 81 mg orally 

daily with the plan for PCI. From the available evidence 

and the patient’s history, which one of the following is 

most appropriate to initiate for this patient? 

A. Clopidogrel 300 mg LD, followed by 75 mg/day. 




daily. 

22. Answer: D 

The patient is experiencing a non-ST segment elevation 

myocardial infarction with a planned PCI. Answer A and 

Answer C are incorrect because both ticagrelor and prasugrel 

have been proved superior to clopidogrel. The patient 

is 76 years old and had a previous stroke. The subgroup 

older than 75 years in the TRITON trial exhibited no difference 

in the net clinical benefit of prasugrel compared 

with clopidogrel. Additionally, the patients with a previous 

TIA/stroke had worse outcomes compared with clopidogrel 

(Answer B is incorrect). Also in the PLATO trial, the 

efficacy of ticagrelor over clopidogrel was not attenuated by 

age of greater than 75 years or history of ischemic stroke. 

Therefore, Answer D is the best choice. 

1. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus 

clopidogrel in patients with acute coronary syndromes. N Engl 

J Med 2007;357:2001-15. 

PubMed Link 

2. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel 

in patients with acute coronary syndromes. N Engl J 

Med 2009; 361:1045-57. 

PubMed Link 

23. A 70-year-old woman (weight 55 kg) presents to the 

emergency department with chest pain that radiates 

to her jaw and ST-segment depressions on electrocardiography. 

Her medical history is significant for 

diabetes mellitus, hypertension, and chronic kidney 

insufficiency. Laboratory results are hemoglobin 10.5 

g/dL, hematocrit 32%, SCr 1.8 mg/dL, and troponin 

less than 0.2 ng/mL. She is prescribed a heparin intravenous 

infusion and aspirin 325 mg orally daily. The 

medical team has scheduled the patient for a cardiac 

catheterization. From the available evidence and the 

patient’s history, which one of the following is the most 

appropriate antiplatelet regimen to initiate for this 

patient? 





daily. 

23. Answer: C 

This patient is experiencing unstable angina, is taking aspirin 

325 mg orally daily, weighs 55 kg, and is scheduled 

for cardiac catheterization. Answer B is incorrect because 

Answers 

10 


the patient’s weight is 55 kg. In the subgroups from the 

TRITON trial, prasugrel did not show a net clinical benefit 

over clopidogrel in patients who weighed less than 60 

kg. Answer D is incorrect because the patient is taking aspirin 

325 mg orally daily. Aspirin doses of 300 mg or greater 

predicted that clopidogrel would perform better than 

ticagrelor. The 600-mg loading dose of clopidogrel has been 

shown to be superior to 300 mg in this patient population 

(Answer C is correct; Answer A is incorrect). 



J Med 2007;357:2001-15. 

PubMed Link 



Med 2009; 361:1045-57. 

PubMed Link 

3. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability 

in individual responsiveness to clopidogrel: clinical implications, 

management, and future perspectives. J Am Coll Cardiol 

2007;49:1505-16. 

PubMed Link 


emergency department with chest pain, ST-segment 

depressions on electrocardiography, and elevated troponins. 

The patient’s medical history includes diabetes 

mellitus, hypertension, kidney transplantation, and 

previous Aspergillus pneumonia. The patient’s oral 

drugs are tacrolimus 2 mg twice daily, mycophenolate 

500 mg twice daily, voriconazole 200 mg twice daily, 

amlodipine 10 mg/day, aspirin 81 mg/day, pravastatin 

80 mg every evening, and enalapril 10 mg/day. 

Laboratory results are as follows: hemoglobin 11.5 g/ 

dL, hematocrit 34%, and SCr 1.0 mg/dL. From the 

available evidence and the patient’s history, which one 

of the following is the most appropriate antiplatelet 

regimen to initiate in this patient? 





daily. 

24. Answer: B 

This patient presents with a non-ST segment myocardial 

infarction. He is recieving voriconazole for previous 

aspergillus pneumonia and has a history of kidney transplantation 

on tacrolimus. Answer A, Answer C, and Answer 

D are incorrect because significant CYP 3A4 interactions 

can occur with both clopidogrel and ticagrelor. Ticagrelor 

should be avoided in patients prescribed strong CYP 3A4 

inhibitors (e.g., voriconazole). Answer B is correct because 

there are no substantial drug interactions with strong CYP 

3A4 inhibitors and prasugrel. 

1. Bates ER, Lau WC, Angiolillo DJ. Clopidogrel-drug interactions. 

J Am Coll Cardiol 2011;57:1251-63. 

PubMed Link 

2. Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A 

inhibition by ketoconazole affects prasugrel and clopidogrel 

pharmacokinetics and pharmacodynamics differently. Clin 

Pharmacol Ther 2007;81:735-41. 

PubMed Link 




His medical history includes asthma, diabetes 

mellitus, and hypertension. His drugs are amlodipine 

10 mg orally daily, aspirin 325 mg orally daily, atorvastatin 

80 mg orally every evening, and enalapril 10 mg 

orally daily. Laboratory results are hemoglobin 10.5 g/ 

dL, hematocrit 32%, and SCr 1.0 mg/dL. Which one of 

the following would most affect this patient’s long-term 

outcomes if the medical team chose to use ticagrelor as 

the P2Y12 antagonist? 

A. Change the dose of aspirin to 81 mg orally daily. 

B. Educate the patient that his or her pulmonary 

function tests may decrease over time. 

C. Change ticagrelor to prasugrel because it is contraindicated 

in patients with asthma. 

D. Decrease the maintenance dose (MD) of ticagrelor 

to 45 mg orally twice daily because of the 

patient’s weight. 

25. Answer: A 

Answer B and Answer C are incorrect because ticagrelor is 

not contraindicated in asthma and does not effect pulmonary 

function tests. There is a significant increase in dyspnea 

initially with ticagrelor compared with clopidogrel, but this 

is not a contraindication for therapy. The patient should be 

counseled on this potential side effect. Answer D is incorrect 

because there is no weight cutoff for ticagrelor and no 

clinical outcome trial has studied ticagrelor at the 45 mg 

twice daily dosage. Answer A is correct in that those treated 

with aspirin doses less than 100 mg had better clinical outcomes 

with ticagrelor compared with clopidogrel. This has 

led to the recommendation that the maintenance dose of 

aspirin should be less than 100 mg when co-administered 

with ticagrelor. 

1. Storey RF, Becker RC, Harrington RA, et al. Pulmonary function 

in patients with acute coronary syndrome treated with 

ticagrelor or clopidogrel (from the Platelet Inhibition and 

Patient Outcomes [PLATO] pulmonary function substudy). 

Am J Cardiol 2011;108:1542-6. 

PubMed Link 




Med 2009; 361:1045-57. 

PubMed Link 

26. Which one of the following agents has the highest risk 

of fatal bleeding related to the competitor in acute coronary 

syndrome (ACS) in patients receiving PCI? 

A. Prasugrel 10 mg versus clopidogrel 75 mg/day. 

B. Rivaroxaban 2.5 mg twice daily versus placebo. 

C. Rivaroxaban 5 mg twice daily versus placebo. 

D. Vorapaxar 40 mg load; then 2.5 mg/day versus 

placebo. 

26. Answer: A 

Answer B, Answer C, and Answer D are incorrect because 

in their respective phase 3 clinical trials, rivaroxaban and 

vrapaxar did not increase the risk of fatal bleeding related 

to the comparator group. Answer A is correct based on data 

from the landmark TRITON trial. In this study, prasugrel 

significantly increased the risk of fatal bleeding compared 

with clopidogrel. 

1. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in 

patients with a recent acute coronary syndrome. N Engl J Med 

2012;366:9-19. 

PubMed Link 

2. Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist 

vorapaxar in acute coronary syndromes. N Engl J Med 

2012;366:20-33. 

PubMed Link 



J Med 2007;357:2001-15. 

PubMed Link 

27. Which one of the following best represents rivaroxaban’s 

potential role in the management of ACS given 

the available evidence? 

A. Early administration for a patient presenting with 

chest discomfort and ST-segment changes as a 

replacement for unfractionated heparin and lowmolecular-weight 

heparin. 

B. Administration during PCI to prevent stent thrombosis 

as a replacement for bivalirudin. 

C. Initiation just before hospital discharge in addition 

to aspirin and a thienopyridine for secondary prevention 

of ischemic events. 

D. A replacement for warfarin in patients with atrial 

fibrillation (AF). 

27. Answer: C 

The role of rivaroxaban in addition to aspirin or aspirin 

plus a thienopyridine for the secondary prevention of ischemic 

events is based on the ATLAS ACS 2 trial. Answer 

A is incorrect because it does not replace the early anticoagulant 

therapies in ACS. Answer B is incorrect because 

rivaroxaban has not been studied in PCI as a replacement 

for bivalirudin. Although it has label approval for atrial 

fibrillation, rivaroxaban dosing in atrial fibrillation is significantly 

different than the dosing in ACS; therefore, it should 

not be used in that fashion (Answer D is incorrect). Answer 

C is correct based on the inclusion criteria in the ATLAS 

ACS 2 trial. 

1.Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in 

patients with a recent acute coronary sndrome. N Engl J Med 

2012; 366:9-19. 

PubMed Link 

28. A 55-year-old man with ACS receives a stent to the left 

anterior descending artery. Which one of the following 

is most important to consider in choosing between 

ticagrelor and prasugrel for this patient? 

A. Efficacy compared with clopidogrel. 

B. Relative platelet inhibition compared with 

clopidogrel. 

C. Genetic effects on the drugs’ metabolism. 

D. Offset of the antiplatelet effects. 

28. Answer: D 

Answer A is incorrect because both ticagrelor and prasugrel 

have shown superiority over clopidogrel in randomized 

trials, and the populations in these studies were different. 

Based on these data, direct comparisons cannot be made. 

Ticagrelor and prasugrel both have superior platelet inhibition 

compared with clopidogrel (Answer B is incorrect). 

Answer C is incorrect because, to date, there have been no 

genetic effects identified that alter either drug’s metabolism. 

Answer D is correct based on Table 2-4, which compares 

the pharmacokinetic and pharmacodynamic parameters of 

clopidogrel, prasugrel, and ticagrelor. 



Med 2009;361:1045-57. 

PubMed Link 



J Med 2007;357:2001-15. 

PubMed Link 

3. Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind 

assessment of the ONSET and OFFSET of the 

antiplatelet effects of ticagrelor versus clopidogrel in patients 

with stable coronary artery disease: the ONSET/OFFSET 

study. Circulation. 2009;120:2577-85. 

PubMed Link 

Answers 

12 




inhibitor, compared with clopidogrel in healthy humans. Br J 


PubMed Link 

29. Which one of the following best describes the potential 

role for cangrelor in ACS? 

A. As replacement of clopidogrel during PCI. 

B. An addition to clopidogrel during PCI to replace 

glycoprotein IIb/IIIa inhibitors. 

C. As therapy instead of an oral P2Y12 antagonist in 

patients awaiting coronary artery bypass grafting 

(CABG). 

D. As replacement for glycoprotein IIb/IIIa inhibitors 

in the medical management of ACS. 

29. Answer: C 

Based on the CHAMPION PCI and CHAMPION 

PLATFORM clinical trials, cangrelor has not been shown 

to be beneficial in replacing clopidogrel or when added to 

clopidogrel in PCI (Answer A and Answer B are incorrect). 

Answer D is incorrect because cangrelor has not been studied 

in this patient population. Answer C is correct based 

on the BRIDGE trial, which showed that cangrelor could 

be used instead of a P2Y12 antagonist in patients awaiting 

CABG. 

1. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet 

blockade with cangrelor during PCI. N Engl J Med 

2009;361:2330-41. 

PubMed Link 

2. Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition 

with cangrelor in patients undergoing PCI. N Engl J Med 

2009; 361:2318-29. 

PubMed Link 

3. Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet 

therapy with cangrelor in patients undergoing cardiac 

surgery. JAMA 2012;307:265-74. 

PubMed Link 

30. Which one of the following best describes the metabolic 

pathways of clopidogrel and ticagrelor? 

A. Both ticagrelor and clopidogrel are metabolized 

through CYP2D6 . 

B. Ticagrelor is metabolized through CYP2C9 but 

not clopidogrel. 

C. Both clopidogrel and ticagrelor are metabolized 

through CYP3A4. 

D. Ticagrelor is metabolized through CYP2C19 but 

not clopidogrel. 

30. Answer: C 

Clopidogrel is metabolized by CYP3A4, 2B6, 1A2, 2C9, 

and 2C19; ticagrelor is metabolized by CYP 3A4. Therefore, 

Answer A, Answer B, and Answer D are incorrect. Answer 

C is correct in that both clopidogrel and ticagrelor are 

metabolized through CYP3A4. 



PubMed Link 

2. Teng R, Oliver S, Hayes MA, et al. Absorption, distribution, 

metabolism, and excretion of ticagrelor in healthy subjects. 

Drug Metab Dispos 2010;38:1514-21. 

PubMed Link 

31. A 65-year-old man (weight 90 kg) was admitted for non– 

ST-segment elevation myocardial infarction (NSTEMI) 

and treated with a drug-eluting stent (DES). He received 

oral aspirin 325 mg and clopidogrel 600 mg at the time 

of the event and transitioned to MDs of 81 mg/day and 

75 mg/day, respectively. He has continual chest pain 2 

days after his procedure. Before discharge, platelet reactivity 

testing is performed with the VerifyNow P2Y12 

assay, resulting in a PRU of 300. Which one of the following 

is best to recommend for this patient? 

A. Increase clopidogrel dose to 150 mg/day. 

B. Reload clopidogrel 600 mg and continue 75 mg/ 

day. 

C. Reload clopidogrel 600 mg and increase the MD 

to 150 mg/day. 

D. Change to prasugrel 60 mg LD, followed by 10 

mg/day. 

31. Answer: D 

Patients with high post-treatment platelet reactivity have 

been shown be at an increased risk of recurrent CV events. 

Changing to prasugrel is the best choice because it has been 

shown to be superior to standard dosing of clopidogrel in 

the management of NSTEMI with invasive management 

(Answer D is correct). Although altering the dose of clopidogrel 

increases its antiplatelet effects in pharmacodynamic 

studies, these strategies have failed to yield improvements 

in outcomes (Answer A, Answer B, and Answer C are 

incorrect). 

1. Cuisset T, Frere C, Quilici J, et al. High post-treatment platelet 

reactivity identified low-responders to dual antiplatelet therapy 

at increased risk of recurrent cardiovascular events after 

stenting for acute coronary syndrome. J Thromb Haemost 

2006;4:542-9. 

PubMed Link 

2. Gurbel PA, Bliden KP, Guyer K, et al. Platelet reactivity in 

patients and recurrent events post-stenting: results of the 

PREPARE POST-STENTING study. J Am Coll Cardiol 

2005;46:1820-6. 

PubMed Link 


3. CURRENT-OASIS 7 Investigators. Dose comparisons of clopidogrel 

and aspirin in acute coronary syndromes. N Engl J Med 

2010;363:930-42. 

PubMed Link 

4. Price MJ, Berger PB, Teirstein PS, et al. Standard- vs high-dose 

clopidogrel based on platelet function testing after percutaneous 

coronary intervention: the GRAVITAS randomized trial. 

JAMA 2011;305:1097-105. 

PubMed Link 



J Med 2007;357:2001-15. 

PubMed Link 

32. A 70-year-old woman (weight 70 kg) has a medical history 

significant for myocardial infarction (MI) with 

subsequent CABG, diabetes, hypertension, and hyperlipidemia. 

She presents with left arm pain that has 

increased in frequency during the past 48 hours. Her 

electrocardiography shows T-wave inversions, and her 

laboratory results are hemoglobin 12 g/dL, hematocrit 

36%, SCr 0.8 mg/dL, and troponin 8.2 ng/mL. She 

does not wish to undergo catheterization at this time. 

Which one of the following is the optimal antiplatelet 

regimen for this patient? 


B. Clopidogrel 300 mg LD, followed by 75 mg/day. 

C. Prasugrel 60 mg LD, followed by 10 mg/day. 


daily. 

32. Answer: D 

The patient is being managed noninvasively for NSTEMI; 

prasugrel is only appropriate for invasive management 

(Answer C is incorrect). Although clopidigrel could be considered 

an option for this patient’s medical management, 

ticagrelor has been shown to be superior to clopidogrel 

for management of NSTEMI, including in patients who 

are medically managed. This has led to recommendations 

from the American College of Chest Physicians to 

recommend ticagrelor over clopidogrel in this patient population 

(Answer D is correct; Answer A and Answer B are 

incorrect). 



J Med 2007;357:2001-15. 

PubMed Link 



Med 2009;361:1045-57. 

PubMed Link 

3. Vandvik PO, Lincoff M, Gore JM, et al. Primary and secondary 

prevention of cardiovascular disease: antithrombotic therapy 

and prevention of thrombosis, 9th ed: American College of 

Chest Physicians evidence-based clinical practice guidelines. 

Chest 2012;141:e637S-e668S. 

PubMed Link 

33. A 72-year-old man (weight 79 kg) has a medical history 

significant for MI managed medically, diabetes, 

hypertension, and hyperlipidemia. He presents with 

angina that has increased in frequency during the past 

24 hours. Electrocardiography shows ST depressions, 

and laboratory results are hemoglobin 13 g/dL, hematocrit 

39%, SCr 1.4 mg/dL, and troponin 7.1 ng/mL. 

The patient, who previously underwent genetic testing, 

is a noncarrier of the CPY2C19*2 allele. He does not 

wish to undergo catheterization at this time. Which 

one of the following is the most appropriate antiplatelet 

regimen for this patient? 



C. Prasugrel 60 mg LD, followed by 10 mg/day. 


daily. 

33. Answer: D 

This patient is being managed noninvasively for NSTEMI; 

prasugrel is only appropriate for invasive management 

(Answer B and Answer C are incorrect). Ticagrelor has 

been shown to be superior to clopidogrel for management 

of NSTEMI, including in patients who are medically managed 

(Answer D is correct). However, ticagrelor was also 

associated with an increased risk of bleeding events. Despite 

genetic profiling, a 300-mg loading dose is preferred in 

medical management (Answer A is incorrect). 


clopidogrel in patients with acute coronary syndromes. N Engl J 

Med 2007;357:2001-15. 

PubMed Link 


in patients with acute coronary syndromes. N Engl J Med 

2009;361:1045-57. 

PubMed Link 

3. Yusef S, Zhao F, Mehta SR, et al. The Clopidogrel in Unstable 

Angina to Prevent Recurrent Event Trial Investigators. Effects 

of clopidogrel in addition to aspirin in patients with acute coronary 

syndromes without ST-segment elevation. N Engl J Med 

2001;345:494-502. 

PubMed Link 

4. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 

polymorphisms and response to clopidogrel. N Engl J Med 

2009;360:354-62. 

PubMed Link 

5. Holmes MV, Perel P, Shah T, et al. CYP2C19 genotype, clopidogrel 

metabolism, platelet function, and cardiovascular events: a 

systematic review and meta-analysis. JAMA 2011;306:2704-14. 

PubMed Link 

Answers 

14 


34. A 58-year-old man (weight 70 kg) presents with anterior 

STEMI treated with a bare metal stent (BMS) to 

his left anterior descending coronary artery. He is initiated 

on aspirin 81 mg and clopidogrel 600 mg LD, 

followed by 75 mg/day. The following morning, echocardiography 

shows a reduced left ventricular (LV) 

ejection fraction of 30% and the presence of an LV 

thrombus. In addition to continuing aspirin, which one 

of the following is best to recommend for this patient? 

A. Add warfarin (INR 2–3) and clopidogrel for 1 

month only. 

B. Add warfarin (INR 2–2.5) and clopidogrel for 3 

months only. 

C. Add warfarin (INR 2–3) and clopidogrel for 3 

months only. 

D. Add warfarin (INR 2–3) for 3 months and discontinue 

clopidogrel. 

34. Answer: A 

This patient received a BMS after STEMI and now has 

an LV thrombus requiring anticoagulation in addition to 

antiplatelet therapy. Answer B is incorrect because this recommendation 

comes from the ACC/AHA guidelines for 

NSTEMI management in patients with an indication for 

anticoagulation. Answer C and Answer D are incorrect 

because these are American College of Chest Physicians 

guideline recommendations for STEMI patients who have 

received DES or no stents, respectively. Answer A is correct 

because it is consistent with American College of Chest 

Physicians guidelines. 

1. Anderson JL, Adams CD, Antman EM, et al. 2011 ACCF/ 

AHA Focused Update Incorporated Into the ACC/AHA 2007 

Guidelines for the Management of Patients with Unstable 

Angina/Non-ST-Elevation Myocardial Infarction: a report of 

the American College of Cardiology Foundation/American 

Heart Association Task Force on Practice Guidelines. 

Circulation 2011;123:e426-e-579. 

PubMed Link 





Chest 2012;141:e637S-e668S. 

PubMed Link 

35. Which one of the following best describes a pharmacodynamic 

benefit of prasugrel over clopidogrel? 

A. No requirement for activation to exert its effects. 

B. Improved selectivity for the P2Y12 receptor. 

C. Decreased variability in antiplatelet effect. 

D. Lack of CYP3A metabolism. 

35. Answer: C 

Like clopidogrel, prasugrel is a prodrug that requires activation 

through a CYP-dependent process (Answer A is 

incorrect). Both drugs are metabolized by CYP3A and 

do not have differences in binding to the P2Y12 receptor 

(Answers B and Answer D are incorrect). Answer C is correct 

because prasugrel has been consistently shown to have 

more potent and consistent antiplatelet effects. 



inhibitor, compared with clopidogrel in healthy humans. Br J 


PubMed Link 

2. Holmes MV, Perel P, Shah T, et al. CYP2C19 genotype, 

clopidogrel metabolism, platelet function, and cardiovascular 

events: a systematic review and meta-analysis. JAMA 

2011;306:2704-14. 

PubMed Link 




The patient’s medical history includes asthma, 

hypertension, and end-stage kidney disease after 

kidney transplantation. His drugs include amlodipine, 

aspirin, ketoconazole, mycophenolate mofetil, 

omeprazole, pravastatin, and tacrolimus. Which one of 

the following therapy changes would be most appropriate 

if clopidogrel were added to treat this patient’s 

ACS event? 

A. Change amlodipine to diltiazem. 

B. Change pravastatin to atorvastatin. 

C. Change ketoconazole to voriconazole. 

D. Change omeprazole to pantoprazole. 

36. Answer: D 

Although amlodipine and ketoconazole coadministration 

have been linked with reductions in antiplatelet effects of 

clopidogrel, no data link them to worse clinical outcomes 

(Answer A and Answer C are incorrect). Additionally, 

changing amlodipine to diltiazem could lead to an increase 

in tacrolimus serum concentrations because diltiazem may 

inhibit the metabolism of tacrolimus. Answer B is incorrect 

in that atorvastatin has been reported to increase cardiovascular 

events when combined with clopidogrel; however, 

these reports are inconsistent. Pantoprazole is one of the 

PPIs that has not been linked with adverse CV events in any 

of the reported analyses (Answer D is correct). 

1. Farid NA, Payne CD, Small DC, et al. Cytochrome P450 3A 

inhibition by ketoconazole affects prasugrel and clopidogrel 

pharmacokinetics and pharmacodynamics differently. Clin 

Pharmacol Ther 2007;81:735-41. 

PubMed Link 


2. Gremmel T, Steiner S, Seidinger D, et al. Calcium-channel 

blockers decrease clopidogrel-mediated platelet inhibition. 

Heart 2010;96:186-9. 

PubMed Link 



PubMed Link 

37. You are asked to provide a recommendation for a 

formulary decision on clopidogrel, prasugrel, and 

ticagrelor for use in your institution in patients admitted 

with ACS. Which one of the following strategies is 

most cost-effective given the currently available data? 

A. Provide universal use of prasugrel for all patients. 

B. Genotype patients and use prasugrel for those with 

loss-of-function (LOF) alleles for clopidogrel. 

C. Provide universal use of ticagrelor for all patients. 

D. Genotype patients and use ticagrelor for those 

with LOF alleles for clopidogrel. 

37. Answer: C 

Answer A and Answer B are incorrect because while both 

universal and genotype-directed prasugrel have been found 

to be cost-effective compared with clopidogrel, they have 

not been shown to be better than ticagrelor. Universal 

ticagrelor was shown to be better than genotype-based 

ticagrelor (Answer C is correct; Answer D is incorrect). 

1. Mahoney EM, Wang K, Arnold SV, et al. Cost-effectiveness of 

prasugrel versus clopidogrel in patients with acute coronary 

syndromes and planned percutaneous coronary intervention: 

results from the trial to assess improvement in therapeutic 

outcomes by optimizing platelet inhibition with Prasugrel- 

Thrombolysis in Myocardial Infarction TRITON-TIMI 38. 

Circulation 2010;121:71-9. 

PubMed Link 

2. Lee S, Dhamija A, Parsons K, et al. Cost-effectiveness of universal 

or genotype driven use of available dual antiplatelet 

strategies in patients with acute coronary syndrome [abstract]. 

J Am Coll Cardiol 2012;59:E483. 

Internet Link 

3. Crespin DJ, Federspiel JJ, Biddle AK, et al. Ticagrelor versus 

genotype-driven antiplatelet therapy for secondary prevention 

after acute coronary syndrome: a cost-effectiveness analysis. 

Value in Health 2011;14:483-91. 

PubMed Link 

4. Reese ES, Mullins D, Beitelshees AL, et al. Cost-effectiveness 

of cytochrome P450 2C19 genotype screening for selection 

of antiplatelet therapy with clopidogrel or prasugrel. 

Pharmacotherapy 2012;32:323-32. 

PubMed Link 



depressions on electrocardiography, and an increased 

troponin level of 4.5 ng/mL. Laboratory results are 

hemoglobin 12 g/dL, hematocrit 36%, and SCr 1.0 

mg/dL. His medical history is significant for AF 

(annual stroke risk < 3% per year), upper gastrointestinal 

bleed, and hypertension. The patient’s oral drugs 

are chlorthalidone 25 mg daily, metoprolol tartrate 50 

mg twice daily, and warfarin 5 mg daily. He receives 

a DES, and he is treated with aspirin 81 mg/day and 

clopidogrel 75 mg/day. Which one of the following 

changes to the patient’s home drugs would be best 

before his discharge? 

A. Add omeprazole. 

B. Add pantoprazole. 

C. Add ranitidine. 

D. Discontinue warfarin. 

38. Answer: D 

The patient has been treated with DES placement after 

NSTEMI and has atrial fibrillation on warfarin therapy 

before admission. In light of the patient’s low risk of stroke 

from atrial fibrillation (hypertension being his only risk 

factor), he does not require anticoagulation, particularly 

in light of his gastrointestinal bleeding history. Although 

Answer A, Answer B, and Answer C represent options for 

potenitally reducing the risk of gastrointestinal bleeding in 

patients requiring triple antithrombotic therapy, they are all 

incorrect because this patient has a low risk of stroke and a 

high risk for increased bleeding, making Answer D correct. 





Chest 2012;141:e637S-e68S. 

PubMed Link 

2. Wann LS, Curtis AB, January CT, et al. 2011 ACCF/AHA/ 

HRS focused update on the management of patients with 

atrial fibrillation (updating the 2006 guideline): a report of the 

American College of Cardiology Foundation/American Heart 

Association Task Force on Practice Guidelines. Circulation 

2011;123:104-23. 

PubMed Link 

39. Which one of the following patients treated for ACS 

would most likely experience harm if treated with prasugrel 

over clopidogrel therapy? 

A. A 73-year-old patient (weight 70 kg) with a history 

of TIA treated for NSTEMI with DES 

implantation. 

B. A 75-year-old patient with diabetes (weight 80 kg) 

treated for STEMI with DES implantation. 

Answers 

16 


C. A 70-year-old patient (weight 90 kg) treated for 

NSTEMI with medical management. 

D. A 71-year-old patient (weight 58 kg) treated for 

NSTEMI with BMS implantation. 

39. Answer: A 

Patients aged 75 years or older or weighing 60 kg or under 

were found to have no net benefit with prasugrel therapy, 

but also no net harm (Answer B and Answer D are incorrect). 

The medically managed subgroup was found to 

have an insignificant difference in outcomes with prasugrel 

but again no net harm (Answer C is incorrect). The 

only subgroup found to have experienced net harm in the 

TRITON-TIMI 38 trial was patients with history of stroke 

or TIA (Answer A is correct). 



J Med 2007;357:2001-15. 

PubMed Link 

2. Pride YB, Wiviott SD, Buros JL, et al. Effect of prasugrel versus 

clopidogrel on outcomes among patients with acute coronary 

syndrome undergoing percutaneous coronary intervention 

without stent implantation: a TRial to assess Improvement in 

Therapeutic Outcomes by optimizing platelet inhibitioN with 

prasugrel (TRITON)-Thrombolysis in Myocardial Infarction 

(TIMI) 38 substudy. Am Heart J 2009;158:e21-6. 

PubMed Link 

40. Which one of the following patients would have the 

greatest risk of death or reinfarction after an ACS 

event? 

A. A 65-year-old man with ST depressions on electrocardiography, 

troponin 12.2 ng/mL, and 

previously diagnosed 40% stenosis in the right coronary 

artery. 

B. A 70-year-old woman with ST depressions on electrocardiography, 

negative troponin, and reported 

aspirin use until the day of admission. 

C. A 60-year-old man with ST depressions on electrocardiography, 

troponin 17.1 ng/mL, and reported 

nitroglycerin use within 7 days. 

D. A 62-year-old woman with ST depressions on 

electrocardiography, troponin 11.5 ng/mL, previously 

diagnosed 60% stenosis in the left anterior 

descending artery, and reported aspirin use until 

the day of admission. 

40. Answer: D 

Based upon the TIMI risk score, the following have been 

identified as risk factors for death, MI, or urgent revascularization: 

age 65 years or greater; three or more CAD risk 

factors; prior coronary stenosis of 50% or greater; aspirin 

use within 7 days; elevated biomarkers; and ST deviation. 

That makes the patient in Answer D the correct response. 

The patients described in Answer A, Answer B, and Answer 

C have lower risk. 

1. Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk 

score for unstable angina/non-ST elevation MI: a method 

for prognostication and therapeutic decision making. JAMA 

2000;284:835-42. 

PubMed Link 

2. Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA 

focused update of the guideline for the management of patients 

with unstable angina/Non–ST-elevation myocardial infarction 

(updating the 2007 guideline and replacing the 2011 focused 

update): a report of the American College of Cardiology 

Foundation/American Heart Association Task Force on practice 

guidelines. Circulation 2012;126:875-910. 

PubMed Link 

3. Kushner SG, Hand M, Smith SC Jr, et al. 2009 Focused Updates: 

ACC/AHA Guidelines for the Management of Patients 

With ST-Elevation Myocardial Infarction (updating the 2004 

Guideline and 2007 Focused Update) and ACC/AHA/SCAI 

Guidelines on Percutaneous Coronary Intervention (updating 

the 2005 Guideline and 2007 Focused Update): a report of the 

American College of Cardiology Foundation/American Heart 

Association Task Force on Practice Guidelines. Circulation 

2009;120:2271-306. 

PubMed Link 

Newer Anticoagulation Strategies 

in Atrial Fibrillation 

Questions 41–43 pertain to the following case 

M.M. is a 67-year-old man with a history of hypertension, 

diabetes, and mitral stenosis secondary to rheumatic 

heart disease. He presents to the cardiology clinic for follow-up. 

His heart rate is 82 beats/minute, but the rhythm 

is determined to be irregularly irregular during physical 

examination. Electrocardiography reveals atrial fibrillation 

(AF). On previous echocardiography, M.M. was found 

to have a dilated left atrium secondary to mitral stenosis; 

this is currently being medically managed. Results of his 

complete blood cell count (CBC), activated partial thromboplastin 

time (aPTT), PT/INR, and basic metabolic panel 

(BMP) are within normal limits, and his fasting blood glucose 

is 123 mg/dL. He currently takes aspirin 325 mg/day, 

simvastatin 40 mg at bedtime, lisinopril 20 mg/day, and 

metformin 1000 mg twice daily. 

41. Given his medical history, which one of the following is 

M.M.’s strongest single risk factor for stroke as a result 

of AF? 

A. Age. 

B. Mitral stenosis. 

C. Diabetes. 

D. Hypertension. 


41. Answer: B 

Mitral stenosis is considered a major risk factor for stroke 

according to ACC/AHA/HRS and ACCP atrial fibrillation 

(AF) guidelines (Answer B is correct). Answer A, Answer 

C, and Answer D are considered moderate risk factors and 

are therefore incorrect as single risk factors. 

1. Yamamoto K, Ikeda U, Seino Y, et al. Coagulation activity is 

increased in the left atrium of patients with mitral stenosis. J 

Am Coll Cardiol 1995;25:107-12. 

PubMed Link 

2. You JJ, Dinger DE, Howard PA, et al. Antithrombotic therapy 

for atrial fibrillation: antithrombotic therapy and 

prevention of therombosis, 9th edition: American College of 

Chest Physicians Evidence-Based Clinical Practice Guidelines. 

Chest 2012; 141(suppl 2); e531S-e575S. 

PubMed Link 

42. Which one of the following best describes M.M.’s risk 

of ischemic stroke secondary to AF? 

A. Extremely low. 

B. Low. 

C. Intermediate. 

D. High. 

42. Answer: D 

Based on either his CHADS 2 

score of 2 or greater or the 

presence of mitral stenosis alone, this patient would be classified 

as having a high risk of stroke (Answer D is correct). 

Extremely low is not a recognized categorization of stroke 

risk in AF (Answer A is incorrect). Answer B is incorrect 

because a CHADS 2 

score of 0 would equate to low risk. 

Answer C is therefore also incorrect because a CHADS 2 

score of 1 would equate to intermediate risk. 






PubMed Link 




PubMed Link 

43. Which one of the following antithrombotic regimens 

would be best to recommend for M.M. to prevent ischemic 

stroke caused by AF? 

A. Aspirin plus clopidogrel. 

B. Dabigatran. 

C. Rivaroxaban. 

D. Warfarin. 

43. Answer: D 

Answer D is correct because the patient has mitral stenosis, 

and it is strongly indicated that the origin of the patient’s AF 

is valvular. Warfarin is the only drug recommended in this 

scenario. Answer A is incorrect because the patient’s stroke 

risk, in the absence of contraindications, warrants the use of 

anticoagulant therapies because of the superior risk reduction 

versus antiplatelet therapies. Answer B and Answer 

C are incorrect because patients with valvular AF were 

excluded from clinical analysis with these therapies, and 

these agents should not be considered first-line options. 






PubMed Link 




PubMed Link 


L.D., a 68-year-old woman with a history of permanent AF 

after a failed ablation, currently receives rate-controlling 

therapy. She has early-onset mild Alzheimer dementia as 

well as a history of chronic obstructive pulmonary disease, 

tobacco abuse, and medication nonadherence. She lives 

alone and has regular home health assistance in preparing 

her pillbox for the week. Her current drugs are warfarin 5 

mg/day alternating with 7.5 mg (current INR 2.6), donepezil 

5 mg/day, aspirin 81 mg/day, tiotropium 18 mcg/day, 

and fluticasone/salmeterol 250/50 twice daily. Because of 

her dementia, she depends on her pillbox as a memory aid. 

She has difficulty in getting to her anticoagulation clinic 

appointments and in maintaining a consistent diet, leading 

to the necessity of frequent monitoring of her INR. 

However, her previous 6 months of anticoagulation visits 

have demonstrated excellent INR control. Her CBC and 

BMP are within normal limits. 

44. Which one of the following best describes L.D.’s stroke 

risk, a consequence of AF, using the CHADS 2 

and the 

CHA 2 

DS 2 

VASc scores, respectively? 

A. Low, intermediate. 

B. Low, high. 

C. High, high. 

D. Intermediate, high. 

44. Answer: B 

The patient has none of the risk factors that are components 

of the CHADS 2 

score. Therefore, her score would be zero, 

and her risk assessment would be considered low (Answer 

C and Answer D are incorrect). This patient has two risk 

Answers 

18 


factors according to the CHA 2 

DS 2 

VASc system: female sex 

and age older than 65. A score of 2 or greater according to 

the HA 2 

DS 2 

VASc system is considered a high risk of stroke 

(Answer A is incorrect, Answer B is correct). 

1. Odum LE, Cochran KA, Aistrope DS, et al. The CHADS(2) 

versus the new CHA(2) DS(2) -VASc scoring systems for 

guiding antithrombotic treatment of patients with atrial fibrillation: 

review of the literature and recommendations for use. 

Pharmacotherapy 2012;32:285-96. 

PubMed Link 






PubMed Link. 

45. Which one of the following is the best option to 

decrease L.D.’s risk of bleeding from antithrombotic 

therapy? 

A. Discontinue warfarin; initiate rivaroxaban 20 mg/ 

day. 

B. Continue warfarin; target an INR of 1.6–2.5. 

C. Continue warfarin at current dose; discontinue 

aspirin. 

D. Discontinue warfarin; add clopidogrel to aspirin 

therapy. 

45. Answer: C 

This patient does not appear to have an indication for concomitant 

use of aspirin and anticoagulant therapy, and the 

use of aspirin plus warfarin represents a pharmacodynamic 

drug-drug interaction, which increases the risk of bleeding 

events (Answer C is correct). Answer A may be an option if 

the patient was having frequent supratherapeutic INR values, 

but is less important at this point than Answer C because 

her INR today is currently within the therapeutic range at 

2.6 and she has demonstrated excellent INR control over the 

previous 6 months. Additionally, the patient’s history of nonadherence 

and known mild dementia would not be optimal 

circumstances for pursuing a narrower INR range (Answer A 

is incorrect; Answer C is correct). Answer B is a recommendation 

from the ACC/AHA/HRS AF guidelines for patients 

at high risk of bleeding and age greater than 75. However, 

this patient does not have specific high-risk features associated 

with bleeding and is younger than 75 years. Answer D 

is incorrect given that the combination of aspirin and clopidogrel 

is inferior to warfarin in the prevention of stroke and 

would not change the risk of bleeding. 

1. Hansen ML, Sørensen R, Clausen MT, et al. Risk of bleeding 

with single, dual, or triple therapy with warfarin, aspirin, and 

clopidogrel in patients with atrial fibrillation. Arch Intern Med 

2010;170:1433-41. 

PubMed Link 


HRS focused update on the management of patients with atrial 

fibrillation (updating the 2006 guideline). J Am Coll Cardiol 

2011;57:223-42. 

PubMed Link 

46. Considering her CHA 2 

DS 2 

VASc score, which one of 

the following antithrombotic options would best help 

L.D. decrease the number of clinic visits, given the difficulties 

she has with transportation? 

A. Discontinue warfarin; add clopidogrel to aspirin 

therapy. 

B. Continue warfarin, but change the INR goal to 

1.6–2.5. 

C. Discontinue warfarin; add dabigatran 150 mg 

twice daily. 

D. Discontinue warfarin; add rivaroxaban 20 mg 

once daily. 

46. Answer: D 

The combination of aspirin and clopidogrel is inferior to 

warfarin in stroke prevention in AF and should only be considered 

in patients who are not candidates for anticoagulant 

therapy (Answer A is incorrect). Answer B could be considered 

to lower this patient’s risk of bleeding, but the narrower 

INR range will likely increase her need for clinic visits and 

increase monitoring (Answer B is incorrect). Answer C is 

also reasonable, but the patient appears to rely heavily on 

a memory aid with a pillbox and has a history of nonadherence. 

Dabigatran cannot be removed from the product 

container and placed into such a device (Answer A is incorrect, 

Answer D is correct). 




2011;57:223-42. 

PubMed Link 

2. Spinler SA, Willey VJ. A patient’s guide to taking dabigatran 

etexilate. Circulation 2011;124:e209-e211. 

PubMed Link 

47. L.D. shows interest in testing her INR at home after 

reading about it in “Anticoagulation Weekly.” Her 

Medicare plan will provide reimbursement for the 

cost of the device and testing strips. Which one of the 

following represents the most significant barrier to a 

self-testing strategy for L.D.’s warfarin? 

A. A likely increase in the number of her clinic visits 

over time. 

B. Increasing drug acquisition costs for her warfarin. 


C. Reimbursing the anticoagulation provider for 

telephonic management. 

D. Fulfilling competency requirements. 

47. Answer: D 

This patient’s history of nonadherence, reliance on home 

health to assist in drug administration, and presence of 

dementia make her a poor candidate for fulfilling competency 

requirements to use the device (Answer D is 

correct). Answer A is incorrect because it is likely clinic 

visits will decrease over time with self-testing, although 

they may increase initially. Reimbursement for telephonic 

management is also likely not a significant barrier given 

that many anticoagulation practitioners recommend and 

follow patients who are self-testing despite the lack of program 

reimbursement (Answer C is incorrect). Answer B 

is also incorrect because of the relatively low drug acquisition 

costs associated with warfarin; it is also unlikely that 

any change in testing strategy would significantly alter drug 

expenditure with warfarin. 

1. Bussey HI, Bussey M. Cardiology patient page. Warfarin 

management: international normalized ratio self-testing and 

warfarin self-dosing. Circulation 2012;126:e52-4. 

PubMed Link 

2. Bloomfield HE, Krause A, Greer, et al. Meta-analysis: Effect 

of patient self-testing and self-management of long-term anticoagulation 

on major clinical outcomes. Ann Intern Med 

2011;154:472-82. 

PubMed Link 

48. Compared with usual management, which one of the 

following best describes the utility of patient self-testing for 

warfarin? 

A. It achieves superior time in therapeutic range. 

B. It achieves superior clinical outcomes. 

C. It improves quality of life. 

D. Devices are expensive and not reimbursed by 

insurance. 

48. Answer: C 

In the THINRS study, the largest randomized trial of selftesting 

versus usual management, self-testing demonstrated 

statistically significant time in therapeutic range (TTR) compared 

with usual care. However, both groups had TTR in the 

60% range, which likely indicates that the difference is not 

clinically significant (Answer A is incorrect). Furthermore, 

THINRS did not demonstrate any significant difference in 

clinical outcomes (Answer B is incorrect). However, quality 

of life was significantly improved in patients receiving 

self-testing versus usual care (Answer C is correct). Answer 

D is incorrect because self-testing devices are reimbursed 

by many insurance plans. 

1. Gadisseur AP, Breukink-Engbers WG, van der Meer FJ, et 

al. Comparison of the quality of oral anticoagulant therapy 

through patient self-management and management by specialized 

anticoagulation clinics in the Netherlands: a randomized 

clinical trial. Arch Intern Med 2003;163:2639-46. 

PubMed Link 

2. Gardiner C, Williams K, Longair I, et al. A randomised 

control trial of patient self-management of oral anticoagulation 

compared with patient self-testing. Br J Haematol 

2006;132:598-603. 

PubMed Link 


T.W. is a 78-year-old man with a history of paroxysmal AF, 

currently rhythm controlled on dronedarone. Despite several 

trials of antiarrhythmic drug therapy he continues 

to experience palpitations; therefore he is scheduled to 

undergo left atrial ablation later in the week. His medical 

history includes hypertension, hyperlipidemia, depression, 

and osteoarthritis. Currently, T.W. is receiving no anticoagulant 

therapy after experiencing a hemopneumothorax on 

warfarin after a car crash. His electrophysiologist will perform 

transesophageal echocardiography before ablation. 

T.W.’s drug regimen is aspirin 81 mg/day, atorvastatin 20 

mg/day, dronedarone 400 mg twice daily, and citalopram 

20 mg/day. 

49. Which one of the following would best prevent preprocedure 

and inter-procedure thrombus formation 

and minimize the bleeding risk during left atrial ablation 

for T.W.? 

A. Start warfarin as an adjunct to procedural 

therapies. 

B. Start dabigatran and hold the morning dose 

before the procedure. 

C. Continue aspirin and administer inter-procedural 

heparin. 

D. Start dabigatran and give it without interruption 

through the procedure. 

49. Answer: C 

Answer A would be reasonable to continue if the patient 

was already receiving warfarin, but it is not recommended 

that warfarin be initiated in a patient naïve to therapy before 

ablation (Answer A is incorrect). Answer B and Answer D 

are incorrect because the use of dabigatran before ablation 

procedures is associated with worsened clinical outcomes, 

even when the morning dose is held. Answer C is correct 

because intra-procedural anticoagulant therapy is necessary 

for preventing inter-procedure thrombus formation, 

even if preprocedural echocardiography is performed. This 

patient’s current antithrombotic prophylaxis should be 

continued pre-procedure. 

Answers 

20 





2011;57:223-42. 

PubMed Link 






PubMed Link 

50. The procedure is successful. Which one of the following 

is the optimal length of anticoagulant therapy after 

left atrial ablation for T.W.? 

A. 1 month. 

B. 2 months. 

C. 1 year. 

D. Indefinitely. 

50. Answer: D 

This patient has a CHADS 2 

score of 2, indicating a high 

risk of stroke. A minimum duration of 2 months of anticoagulation 

after left atrial ablation is indicated, with the risk 

thereafter to be determined by the CHADS 2 

score. Given 

the patient’s high risk of stroke, Answer D is correct. The 

minimum duration of anticoagulation recommended postablation 

(2 months) could be considered given that he 

was not receiving anticoagulation before the procedure. 

However, the risk of bleeding in this patient appears to be 

attributable to a traumatic event in the setting of anticoagulation 

and does not represent a contraindication to current 

treatment (Answer B is incorrect). Durations of 1 month 

and 1 year are not timeframes that are addressed in the management 

of antithrombotic therapy with ablation (Answer 

A and Answer C are incorrect). 




2011;57:223-42. 

PubMed Link 






PubMed Link 

51. Two weeks after ablation, T.W. reports to the clinic 

feeling well. He has continued taking dronedarone, 

and after his ablation, he was placed on dabigatran 150 

mg twice daily. He reports significant reflux that his 

primary physician told him is likely caused by dabigatran. 

The physician recommended omeprazole 40 mg/ 

day, which has not helped significantly. Which one of 

the following is best to recommend for T.W.? 

A. Continue dabigatran; increase omeprazole to 40 

mg twice daily. 

B. Discontinue dabigatran; start warfarin with target 

INR 1.6–2.5. 

C. Discontinue dabigatran; start rivaroxaban 20 mg/ 

day. 

D. Discontinue dabigatran; start aspirin 81 mg/day 

plus clopidogrel 75 mg/day. 

51. Answer: C 

Answer C is correct because this likely represents an 

adverse reaction from the dabigatran and probably should 

not be continued. Given that the patient is still within the 

2-month window of risk from the ablation procedure, simply 

starting warfarin without a parenteral bridge will likely 

result in a period of subtherapeutic anticoagulation and 

is not recommended; the INR range is also unnecessarily 

restrictive (Answer B is incorrect). Answer A likely will 

not be very effective; additionally, the potential of a drug 

interaction with intensive acid-suppressive therapy and the 

combination of a p-glycoprotein inhibitor with dronedarone 

is concerning (Answer A is incorrect). Answer D is 

incorrect because aspirin plus clopidogrel are inferior to 

anticoagulant therapy in stroke prevention in AF and are 

not recommended after ablation. 






PubMed Link 

2. Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral 

thrombin inhibitor. Circulation 2011: 123:1436-50. 

PubMed Link 


Y.G. is a 68-year-old man with hypertension, hemodialysis-dependent 

end-stage kidney disease, and a history of 

hepatitis C with moderate-severe liver dysfunction. He 

was given a diagnosis of AF after a recent admission for a 

gastrointestinal bleed, but he reports being asymptomatic. 

His laboratory results reveal SCr 4.8 mg/dL, potassium 4.7 

mEq/L, AST 56 IU/L, and ALT 325 IU/L. His INR is 1.6, 

and he is scheduled for hemodialysis later today. Y.G.’s home 

drugs include amlodipine 10 mg/day, metoprolol 50 mg 

twice daily, a “kidney vitamin,” lactulose three times/day, 

clonidine 0.3 mg three times/day, and calcium acetate 667 

mg three times/day with meals. He has been actively listed 

for a kidney plus liver transplant for the past 5 months. 


52. Which one of the following best describes Y.G.’s stroke 

risk and bleeding risk according to the CHADS 2 

and 

HASBLED scores, respectively? 

A. Low, high. 

B. Intermediate, high. 

C. Intermediate, low. 

D. High, high. 

52. Answer: B 

The patient has one risk factor according to the CHADS 2 

score, which is hypertension. Therefore, his score is 1, and 

his risk of stroke would be considered intermediate. He has 

at least five risk factors for bleeding, including age older 

than 65, recent bleeding, abnormal liver function, abnormal 

kidney function, and history of hypertension, placing 

him at high risk of a bleeding event (Answer B is correct). 

Answer A, Answer C, and Answer D incorrectly assess the 

risk of stroke and/or bleeding. 






PubMed Link 

2. Gallego P, Roldan V, Torregrosa JM, et al. Relation of the HAS- 

BLED bleeding risk score to major bleeding, cardiovascular 

events, and mortality in anticoagulated patients with atrial 

fibrillation. Circ Arrhythm Electrophysiol 2012;5:312-8. 

PubMed Link 

53. According to the ACCP 2012 guidelines, which one of 

the following antithrombotic strategies is most appropriate 

for Y.G. to balance his risk of stroke and bleeding? 

A. Warfarin targeting an INR of 2.5-3.5. 

B. Aspirin 81 mg/day plus clopidogrel 75 mg/day. 

C. Aspirin 81 mg/day. 

D. No antithrombotic therapy indicated. 

53. Answer: C 

Given that the patient has an intermediate risk of stroke and 

a high risk of bleeding, Answer C likely represents the best 

answer according to the ACCP guidelines (Answer C is 

correct). Anticoagulation with warfarin would likely place 

this patient at high risk of a bleeding event, and the INR 

is higher than recommended for stroke prevention in atrial 

fibrillation (2.0-3.0) (Answer A is incorrect). Answer B is 

a reasonable for a patient with intermediate risk, but it is 

not recommended by ACCP if the reason for not choosing 

anticoagulation-based therapy is major bleeding risk given 

that aspirin plus clopidogrel did not significantly differ in 

major bleeding risk from warfarin in the ACTIVE study 

(Answer B is incorrect). Answer D is also not appropriate 

given that the patient is not at low risk of stroke and should 

receive some type of antithrombotic therapy (Answer D is 

incorrect). 






PubMed Link 

2. ACTIVE Writing Group of the ACTIVE Investigators. 

Clopidogrel plus aspirin versus oral anticoagulation for atrial 

fibrillation in the Atrial Fibrillation Clopidogrel Trial with 

Irbesartan for Prevention of Vascular Events (ACTIVE W): A 

randomised controlled trial. Lancet 2006;367:1903-12. 

PubMed Link 

54. After discussion, Y.G. expresses a wish to avoid ischemic 

stroke above other concerns, given his hope for 

a future kidney and liver transplant. Which one of the 

following represents the best anticoagulation strategy 

in Y.G., given his comorbidities and risk factors? 

A. Apixaban. 

B. Dabigatran. 

C. Rivaroxaban. 

D. Warfarin. 

54. Answer: D 

Given the patient’s end-stage chronic kidney disease, none 

of the newer anticoagulants can be safely recommended for 

use. Given the significant component of renal elimination 

for these agents, and the lack of established dosing paradigms 

in end-stage kidney disease, Answer A, Answer B, 

and Answer C are incorrect. Warfarin represents the best 

choice because of the ability to monitor and adjust therapy 

in response to the INR and because it is not excreted by 

the kidneys. The presence of moderate to severe liver dysfunction 

may also tilt the selection of anticoagulant therapy 

toward an agent in which therapeutic monitoring is possible 

(Answer D is correct). 






PubMed Link 

2. De Caterina R, Husted S, Wallentin L, et al. New oral anticoagulants 

in atrial fibrillation and acute coronary syndromes. 

ESC Working Group on Thrombosis—Task Force on 

Anticoagulants in Heart Disease position paper. J Am Coll 

Cardiol 2012;59:1413-25. 

PubMed Link 

Answers 

22 


55. Which one of the following is the most important factor 

in selecting an oral anticoagulant in Y.G., given 

near-term transplantation? 

A. Ability to monitor therapy. 

B. Drug-drug interactions. 

C. Reversibility. 

D. Drug acquisition cost. 

55. Answer: C 

In general, cadaveric transplantation requires emergency 

surgery to enhance graft survival and minimize organ ischemia 

time. Therefore, the reversibility of anticoagulation 

effect is a critical factor in drug selection (Answer C is correct). 

The ability to monitor therapy may be important, but 

that depends on the organ systems involved and the associated 

pharmacokinetic properties of the agent employed. 

Therefore, Answer A is incorrect as a general statement. 

Drug-drug interactions may also be significant, but this is 

likely to be after transplantation and is not a consideration 

for pretransplant drug selection (Answer B is incorrect). 

Acquisition cost can also be significant, but it is not the 

most critical factor in this scenario (Answer D is incorrect). 






PubMed Link 





Cardiol 2012;59:1413-25. 

PubMed Link 




2011;57:223-42. 

PubMed Link 

56. The ROCKET-AF trial showed that patients receiving 

rivaroxaban had a higher annual rate of stroke and 

systemic embolism compared with patients receiving 

dabigatran in the RE-LY trial (2.1% vs. 1.1% in 

the 150-mg group). Which one of the following statements 

most accurately describes the reason for this 

difference? 

A. Rivaroxaban is inferior to dabigatran given the 

mechanism of action. 

B. The RE-LY trial used a stronger clinical trial 

design. 

C. The ROCKET-AF trial enrolled higher-risk 

patients. 

D. Rivaroxaban is inferior to dabigatran when dosed 

once daily. 

56. Answer: C 

Patients in ROCKET-AF were only enrolled if they had two 

moderate risk factors for stroke or one major risk factor, 

whereas patients in RE-LY could be enrolled with only one 

risk factor for stroke. As a result, the mean CHADS 2 

score 

was 3.48 in the rivaroxaban group in ROCKET-AF compared 

with 2.2 in the dabigatran group in RE-LY (Answer C 

is correct). Answer A and Answer D are incorrect because 

it is difficult to make a head-to-head comparison between 

therapies across clinical trials that enrolled significantly different 

patient populations and used different clinical trial 

designs. Answer B is also incorrect; the double-dummy 

design used in ROCKET-AF is arguably a stronger design 

than the open-label program used in RE-LY. 

1. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus 

warfarin in nonvalvular atrial fibrillation. N Engl J Med 

2011;365:883-91. 

PubMed Link 

2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus 

warfarin in patients with atrial fibrillation. N Engl J Med 

2009;361:1139-51. 

PubMed Link 


Z.T. is a 60-year-old man admitted to the cardiology service 

after a non–ST-elevation myocardial infarction. He 

received one drug-eluting stent to the proximal left anterior 

descending coronary artery and was doing well the 

following day. He is a smoker (1 pack/day for 20 years) 

and regularly abuses alcohol. Three weeks ago he had an 

upper gastrointestinal bleed after an endoscopy coil embolization. 

He also has paroxysmal AF, currently in normal 

sinus rhythm. Z.T. is having asymptomatic runs of AF on 

telemetry. His current drugs include aspirin 81 mg/day, 

clopidogrel 75 mg/day, simvastatin 40 mg at bedtime, lisinopril 

5 mg/day, and an unfractionated heparin infusion at 

1200 units/hour. Z.T. was receiving warfarin before this 

hospitalization for his AF; on his arrival this was reversed 

with vitamin K and fresh frozen plasma. His BMP and CBC 

are within normal limits, his INR is 1.3, and his aPTT is 75 

seconds, which is therapeutic for heparin according to the 

hospital nomogram. After identification of a bruit on physical 

examination, he is also found to have a vascular fistula at 

the site of his catheterization. 

57. Which one of the following best describes Z.T.’s bleeding 

risk according to the HASBLED score? 

A. Very low. 

B. Low. 

C. Intermediate. 

D. High. 


57. Answer: D 

Z.T. has several risk factors for bleeding. He has a bleeding 

history or predisposition with his recent GI bleed and is currently 

receiving both dual antiplatelet therapy and actively 

abuses alcohol. His HASBLED score is calculated to be 3 

which is considered “high risk” and Answer D is therefore 

correct. Answer A is incorrect as this is not a recognized risk 

categorization for HASBLED. Answers B and C incorrectly 

calculate the risk score based on the patient specific factors. 

1. Lane DA, Lip GYH. Use of the CHA2DS2VASc and HAS- 

BLED scores to aid decision making for thromboprophylaxis 

in nonvalvular atrial fibrillation. Circulation 2012; 126: 860-5. 

PubMed Link 

2. Roldan V, Marin F, Fernandez H, et al. Predictive value of the 

HAS-BLED and ATRIA bleeding cosres for the risk of serious 

bleeding in a “real-world” population with atrial fibrillation 

receiving anticoagulant therapy. Chest 2013; 143 (1): 179-184. 

PubMed Link 

58. Considering his risk factors and other comorbidities, 

which one of the following would be best to recommend 

for Z.T. as antithrombotic therapy for AF? 

A. Continue aspirin and clopidogrel. 

B. Discontinue clopidogrel; start warfarin to target 

INR of 2.0–3.0. 

C. Discontinue clopidogrel; continue aspirin. 

D. Continue aspirin and clopidogrel; start warfarin 

to target INR of 2.0–3.0. 

58. Answer: A 

The patient’s risk of stroke is intermediate, according to 

CHA 2 

DS 2 

VASc, and he is at high risk of bleeding considering 

his drug abuse and recent gastrointestinal bleeding. 

Given this, the use of an anticoagulant to prevent stroke in 

AF is less preferable (Answer B is incorrect). Answer D is 

also incorrect, and the use of “triple therapy” (i.e., dual antiplatelet 

therapy plus an anticoagulant) is associated with a 

high risk of bleeding. In addition, his recent stent placement 

necessitates the use of dual antiplatelet therapy (Answer C 

is incorrect). Answer A is correct because the use of aspirin 

plus clopidogrel is recommended for stroke prevention 

in AF. 

1. Faxon DP, Eikelboom JW, Berger PB, et al. Antithrombotic 

therapy in patients with atrial fibrillation undergoing coronary 

stenting: a North American perspective: executive summary. 

Circ Cardiovasc Interv 2011;4:522-34. 

PubMed Link 

2. Lane DA, Lip GYH. Use of the CHA2DS2VASc and HAS- 

BLED scores to aid decision making for thromboprophylaxis 

in nonvalvular atrial fibrillation. Circulation 2012;126:860-5. 

PubMed Link 

59. Z.T.’s vascular fistula requires surgical correction. 

His antiplatelet therapy will continue given his recent 

stent. Which one of the following is the best statement 

regarding interruption of anticoagulation for 

stroke prevention in AF according to the ACC/AHA/ 

HRS guidelines? 

A. Anticoagulation should not be interrupted for 

any time whatsoever. 

B. A short-term interruption (less than 1 week) is 

reasonable and requires no parenteral bridging. 

C. Parenteral anticoagulation should be reinitiated 

the day after surgery. 

D. A long-term interruption (greater than 1 month) 

is warranted given the clinical scenario. 

59. Answer: B 

The ACC/AHA/HRS guidelines recommend that a 

short-term interruption (less than 1 week) is reasonable 

in patients with AF (Answer B is correct). Answer A is 

incorrect given the patient’s impending surgery. Answer 

C is also incorrect given that anticoagulation soon after 

surgery may introduce a significant risk of bleeding and 

is unnecessary. Answer D is incorrect because it attributes 

the incorrect time frame to the ACC/AHA/HRS 

recommendation. 



atrial fibrillation (updating the 2006 guideline). J Am Coll 

Cardiol 2011;57:223-42. 

PubMed Link 


for atrial fibrillation: antithrombotic therapy and prevention 

of therombosis, 9th edition: American College of Chest 

Physicians Evidence-Based Clinical Practice Guidelines. 


PubMed Link 

60. The following alerts to prescribers, nurses, or pharmacists 

are being considered for new oral anticoagulants 

used within an acute care health system. Which one 

of the following would best prevent an anticoagulation-related 

medication error? 

A. To prescribers that dabigatran results in 

significantly less intracerebral hemorrhage 

than warfarin when used as a stroke prevention 

strategy in AF. 

B. To pharmacists that display serum creatinine 

when warfarin is verified. 

C. To nurses that the dabigatran capsule should not 

be opened, chewed, or crushed. 

D. To nurses that dabigatran may cause dyspepsia. 

Answers 

24 


60. Answer: C 

The dabigatran capsule cannot be opened or manipulated 

in any way because doing so increases the bioavailability 

significantly and exposes the patient to a greater degree 

of anticoagulation than intended (Answer C is correct). 

Answer A may be a reasonable way to increase the use 

of dabigatran, but it is not a medication-error prevention 

strategy (Answer A is incorrect). Answer B would not be 

effective because warfarin use is not significantly affected 

by renal clearance (Answer B is incorrect). Answer D is 

also incorrect because, although it is useful to acknowledge 

potential adverse drug reactions, this is not likely to 

minimize the chance of a medication error. 





Cardiol 2012; 59:1413-25. 

PubMed Link 



atrial fibrillation (updating the 2006 guideline). J Am Coll 

Cardiol 2011;57:223-242. 

PubMed Link

Cardiology/Endocrinology - ACCP

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