Preservation of left ventricular function appears to play a key role in the bisoprolol-induced beneficial effects on prognosis in heart failure. Short-term beta-blocker-induced cardiac effects could provide a means to identify those patients who will experience improved survival over the long term.

Background-Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors(PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs. Methods and Results-The FAST-MI registry included 3670 patients (2744 clopidogrel-and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; Pϭ0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; Pϭ0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. Conclusion-PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00673036. Editorial see p 468 Clinical Perspective on p 482Recent pharmacokinetic and pharmacodynamic studies have investigated the effect of concomitant PPI therapy on the antiplatelet response elicited by clopidogrel. 6 -12 Overall, these studies showed that the coadministration of omeprazole, one of the most potent inhibitors of CYP2C19, was associated with reduced platelet inhibition compared with clopidogrel alone 6,7,10 and that PPI use overall was associated with increased platelet aggregation and was an independent predictor of high residual platelet reactivity in patients receiving clopidogrel. 8,9 However, studies also suggest that less potent inhibitors of CYP2C19 such as pantoprazole do not affect the platelet response to clopidogrel. 11,12 Although a reduction in platelet inhibition would be expected to manifest as a reduction in the clinical efficacy of clopidogrel therapy, recent clinical outcome studies have reported conflicting results. Several small studies [13][14][15] and retrospective analyses of 3 larger population-based studies 16 -18 8,19,20 In light of these conflicting results from controlled clinical trials, further lar...