michigan hypertension core curriculum - State of Michigan

Learning Objectives
204 Hypertension Core Curriculum
Principles of Combination Therapy
Kiran Saraiya DO and Jason Biederman DO, FACOI, FASN
• Combination therapy with two or more antihypertensive medications increases efficacy and
reduces adverse outcomes.
• When reductions in systolic blood pressure of greater than 20 mm Hg or diastolic pressure
of greater than 10 mm Hg are necessary to achieve goal, combination therapy is usually
necessary and should be considered at the initial evaluation.
• Blood pressure lowering medication combinations most likely to result in additive or synergistic
blood pressure reductions based upon their pharmacological profiles are reviewed in this
section.
Pre-test question:
Which of the following statements regarding combination anti-hypertensive therapy is true?
a. Combination therapy is more effective but will result in greater side effects.
b. Combination therapy is more effective and will result in fewer side effects. (Correct)
c. Combination therapy is rarely necessary to achieve target blood pressure recommendations
d. All combinations of two antihypertensive agents will result in additive or synergistic decreases in
blood pressure.
Multiple clinical trials including the Systolic Hypertension in the Elderly Program (SHEP),
Hypertension Optimal Treatment (HOT) study, United Kingdom Prospective Diabetes Study (UKPDS),
Modification of Diet in Renal Disease (MDRD) study, African American Study of Kidney Disease and
Hypertension (AASK), and Appropriate Blood Control in Diabetes (ABCD) trial have demonstrated a
need for multiple drug therapy (often more than three agents) to achieve blood pressure targets in the
majority of patients. Materson et al. showed that only 50% of patients respond to single drug therapy,
regardless of the agent used. 1 However, the majority of patients who “respond” to single drug anti-
hypertensive drug therapy remain above goal BP levels. A meta-analysis of 354 randomized control
trials demonstrated that low dose combination therapy was more efficacious than monotherapy (see
Table 1). The usual maximum (standard) doses of most agents afford only an additional 20% of blood
pressure reduction compared to a half standard dose because many antihypertensive agents (e.g.,
RAAS blockers) have flat dose-response curves. At the same time, maximum doses of medications
may be associated with significantly more side effects. As a consequence, the addition of two
medications at half maximum dose tends to be more effective than the maximum dose of one agent