Understanding and Treating Acute Coronary Syndrome - FreeCE

Page 7Understanding and Treating Acute Coronary Syndrome© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.Reproduction in whole or in part without permission is prohibited.Stanek et alSCAI 2009Juurlink et alCMAJ 2009TRITON-TIMI38ESC 2009PACA TrialJACC 2009COGENTNEJM 2010Study DesignAdditional DataRetrospective cohortanalysis, s/p stentN=16718N=6828 on combinationNested case control, s/p MIreadmit w/MI within 90 dN=734 cases, 2057 controlsCox proportional hazardmodelN=6795 ClopidogrelN=6813 PrasugrelRandomized 104 NSTEMIpts to 2 PPIsRandomized 3761 ACS orDES patients toclopidogrel/omeprazole vsclopidogrel/placeboResults: Increasedrisk of CV eventsYes, HR = 1.51 (pooled)CI=1.39-1.64, p < 0.0001Individual agents had ↑risk, PPIs alone no ↑ riskYes, OR = 1.27 withcurrent PPIsCI=1.03-1.57No, HR = 0.94no increase with PPIcombination for eitherdrugYes, OR = 2.6CI =1.2-6.2 Plateletresponse (VASP) @ 30dto clopidogrel 150 mg/dNo, HR = 0.99CI=0.68-1.44Actually designed to lookat GI endpointPPIEsomeprazole, N=3257Omeprazole, N=2307Pantoprazole, N=1653Lansoprazole, N=785No association withpantoprazoleOR = 1.02Not specifiedNonresponders toclopidogrelOmeprazole 44%Pantoprazole 23%Special formulationcombination productused25Randomized Data: Clopidogrel or PlaceboPost-hoc analysis of the CREDO trial (N = 2116)PCI + Clopidogrel x 4 weeksPlaceboClopidogrelDeath / MI /strokeat 1 yearClopidogrel 7.7%Odds RatioClopidogrel + PPI 13.4% 1.63Placebo 11.1%Placebo + PPI 15.0% 1.55AHA Scientific Sessions 2008, abstract #399926Possible reasons for the observedincreased CV risk• PPIs interfere with the production ofthe clopidogrel active metabolite• PPIs cause direct harm• Confounders in the observational data• e.g., older, sicker patientsSummary• Observational data• Suggest an association between PPI use (particularly withomeprazole) and increased cardiovascular events in patientsreceiving clopidogrel• Randomized data, post-hoc analysis• Suggests PPI use itself is associated with increased cardiovascularevents, regardless of the presence or absence of clopidogrel• Randomized trial, COGENT study (combination product)• Did not find an increase in CV events, although it may have beenunderpoweredhttp://www.theheart.org/heartwire (accessed 6.19.09)2728