s-1743 and Myocardial-Infarction

A primary objective in the application of postmarketing drug safety surveillance is to ascertain the relationship between time-varying drug exposures and recurrent adverse events (AEs) related to health outcomes. The self-controlled case series (SCCS) method is one approach to analysis in this context. It is based on a conditional Poisson regression model, which assumes that events at different time points are conditionally independent given the covariate process. This requirement is problematic when the occurrence of an event can alter the future event risk. In a clinical setting, for example, patients who have a first myocardial infarction (MI) may be at higher subsequent risk for a second. In this work, we propose the positive dependence self-controlled case series (PD-SCCS) method: a generalization of SCCS that allows the occurrence of an event to increase the future event risk, yet maintains the advantages of the original model by controlling for fixed baseline covariates and relying solely on data from cases. As in the SCCS model, individual-level baseline parameters drop out of the PD-SCCS likelihood. Data sources used for postmarketing surveillance can contain tens of millions of people, so in this situation it is particularly advantageous that PD-SCCS avoids doing a costly estimation of individual parameters. We develop expressions for large sample inference and optimization for PD-SCCS and compare the results of our generalized model with the more restrictive SCCS approach.

Topics: Computer Simulation; Esomeprazole; Humans; Lactones; Models, Statistical; Myocardial Infarction; Omeprazole; Product Surveillance, Postmarketing; Research Design; Sulfones

To examine the effect of concomitant use of clopidogrel and PPIs in a national sample of elderly Medicare beneficiaries (age ≥65 years).. A nested case-control design was employed. A cohort of Medicare beneficiaries who initiated clopidogrel and did not have any gap of ≥30 days between clopidogrel fills between July 1, 2006 and December 31, 2008 was identified from a 5% national sample of Medicare claims data. Within this cohort, cases (beneficiaries who experienced any major cardiovascular event [MCE] [acute myocardial infarction, stroke, coronary artery bypass graft, or percutaneous coronary intervention] or all-cause mortality) and controls (beneficiaries who did not experience any MCE or all-cause mortality) were identified from inpatient and outpatient claims. Cases and controls were matched on age and the time to first clopidogrel fill. Conditional logistic regression was performed on the matched sample to evaluate the association between concomitant use of clopidogrel and PPIs and adverse health outcomes (MCEs and all-cause mortality).. A total of 43,159 clopidogrel users were identified. Among them, 15,415 (35.7%) received clopidogrel and a PPI concomitantly at any time during the study period, 3502 (8.1%) experienced a MCE, 7306 (17.1%) died, and a total of 9908 (22.8%) experienced the primary composite outcome (any MCE or all-cause mortality) during follow-up. The odds ratio (OR) for the primary composite outcome was 1.26 (95% confidence interval [CI]: 1.18-1.35). Secondary analyses indicated that elderly patients using clopidogrel and a PPI concomitantly were more likely to experience all-cause mortality (OR: 1.40; 95% CI: 1.29-1.53) as compared to those receiving clopidogrel only, but not MCEs (OR: 1.06; 95% CI: 0.95-1.18).. Concomitant use of clopidogrel and PPIs was associated with a slightly increased risk of all-cause mortality but not MCEs.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aged; Aged, 80 and over; Case-Control Studies; Clopidogrel; Cohort Studies; Coronary Artery Bypass; Drug Interactions; Drug Therapy, Combination; Esomeprazole; Female; Humans; Lansoprazole; Male; Myocardial Infarction; Omeprazole; Pantoprazole; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Rabeprazole; Risk; Stroke; Ticlopidine

The purpose of this study was to determine the readmission rate for acute myocardial infarction (AMI) in patients discharged on clopidogrel and a proton-pump inhibitor (PPI) versus patients discharged on clopidogrel alone after experiencing an AMI and undergoing stent placement. Clopidogrel is a prodrug that requires metabolism in the liver by the cytochrome P450 system (CYP450), in particular cytochrome P450 2C19 (CYP2C19).(1) Recent studies have suggested that medications metabolized by CYP450, such as PPIs, influence the effect of clopidogrel on platelet function(2,3) with an increased risk of cardiovascular events.(4,5) PPIs are often administered with clopidogrel due to the increased bleeding risk of dual antiplatelet therapy, a strategy endorsed by existing consensus guidelines.(6). Treatment with a PPI in combination with clopidogrel would increase the risk of readmission for an AMI after stent placement for AMI.. We collected data on all patients discharged on clopidogrel after stent placement for an AMI between January 2003 and January 2008. Patients were followed for 1 year after their index hospitalization for readmission for an AMI. Rates of readmission were determined for those discharged on clopidogrel alone versus those discharged on clopidogrel and a PPI.. Patients discharged on clopidogrel and a PPI had higher rates of readmission for AMI within 1 year of stent implantation for AMI.. Patients discharged on clopidogrel and a PPI, including esomeprazole and pantoprazole, seem to be at an increased risk of recurrent AMI within 1 year after stent placement for an AMI.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Angioplasty, Balloon, Coronary; Anti-Ulcer Agents; Clopidogrel; Confidence Intervals; Drug Therapy, Combination; Esomeprazole; Female; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Pantoprazole; Patient Readmission; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Recurrence; Retrospective Studies; Risk Factors; Stents; Ticlopidine; Treatment Failure