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Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.

ABSTRACT: BACKGROUND:Proton-pump inhibitors (PPIs) and clopidogrel are frequently coprescribed, although the benefits and harms of their concurrent use are unclear. OBJECTIVE:To examine the association between concurrent use of PPIs and clopidogrel and the risks for hospitalizations for gastroduodenal bleeding and serious cardiovascular disease. DESIGN:Retrospective cohort study using automated data to identify patients who received clopidogrel between 1999 through 2005 after hospitalization for coronary heart disease. SETTING:Tennessee Medicaid program. PATIENTS:20,596 patients (including 7593 concurrent users of clopidogrel and PPIs) hospitalized for myocardial infarction, coronary artery revascularization, or unstable angina pectoris. MEASUREMENTS:Baseline and follow-up drug use was assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious cardiovascular disease (fatal or nonfatal myocardial infarction or sudden cardiac death, stroke, or other cardiovascular death). RESULTS:Pantoprazole and omeprazole accounted for 62% and 9% of concurrent PPI use, respectively. Adjusted incidence of hospitalization for gastroduodenal bleeding in concurrent PPI users was 50% lower than that in nonusers (hazard ratio, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 (CI, 11.7 to 36.9) hospitalizations for gastroduodenal bleeding per 1000 person-years. The hazard ratio associated with concurrent PPI use for risk for serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) for the entire cohort and 1.01 (CI, 0.76 to 1.34) for the subgroup of patients who had percutaneous coronary interventions with stenting during the qualifying hospitalization. LIMITATIONS:Unmeasured confounding and misclassification of exposure (no information on adherence or over-the-counter use of drugs) and end points (not confirmed by medical record review) were possible. Because many patients entered the cohort from hospitals with relatively few cohort members, the analysis relied on the assumption that after adjustment for observed covariates, PPI users from one such hospital could be compared with nonusers from a different hospital. CONCLUSION:In patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with reduced incidence of hospitalizations for gastroduodenal bleeding. The corresponding point estimate for serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk. PRIMARY FUNDING SOURCE:Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute.

SUBMITTER: Ray WA

PROVIDER: S-EPMC3176584 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.

Ray Wayne A WA Murray Katherine T KT Griffin Marie R MR Chung Cecilia P CP Smalley Walter E WE Hall Kathi K Daugherty James R JR Kaltenbach Lisa A LA Stein C Michael CM

Annals of internal medicine 20100301 6

<h4>Background</h4>Proton-pump inhibitors (PPIs) and clopidogrel are frequently coprescribed, although the benefits and harms of their concurrent use are unclear.<h4>Objective</h4>To examine the association between concurrent use of PPIs and clopidogrel and the risks for hospitalizations for gastroduodenal bleeding and serious cardiovascular disease.<h4>Design</h4>Retrospective cohort study using automated data to identify patients who received clopidogrel between 1999 through 2005 after hospita ...[more]

PMID: 20231564

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Project description:ObjectiveTo measure the association between use of proton pump inhibitors and a range of harmful outcomes in patients using clopidogrel and aspirin.DesignObservational cohort study and self controlled case series.SettingUnited Kingdom General Practice Research Database with linked data from the Myocardial Ischaemia National Audit Project (MINAP) and the Office for National Statistics (the cardiovascular disease research using linked bespoke studies and electronic records (CALIBER) collaboration)Population24,471 patients receiving clopidogrel and aspirin.Main outcome measuresThe primary outcome was death or incident myocardial infarction. Secondary outcomes were death, incident myocardial infarction, vascular death, and non-vascular death. Comparisons were made between proton pump inhibitor use and non-use.ResultsOf the 24,471 patients prescribed clopidogrel and aspirin, 12,439 (50%) were also prescribed a proton pump inhibitor at some time during the study. Death or incident myocardial infarction occurred in 1419 (11%) patients while they were receiving a proton pump inhibitor compared with 1341 (8%) who were not receiving a proton pump inhibitor. In multivariate analysis, the hazard ratio for the association between proton pump inhibitor use and death or incident myocardial infarction was 1.37 (95% confidence interval 1.27 to 1.48). Comparable results were seen for secondary outcomes and with other 2C19 inhibitors and with non-2C19 inhibitors. With the self controlled case series design to remove the effect of differences between people, there was no association between proton pump inhibitor use and myocardial infarction, with a rate ratio of 0.75 (0.55 to 1.01). Similarly, with the self controlled case series there was no association with myocardial infarction for other 2C19 inhibitors/non-inhibitors.ConclusionThe lack of a specific association and the discrepancy between findings of the analyses between and within people suggests that the interaction between proton pump inhibitors and clopidogrel is clinically unimportant.

Project description:BackgroundChronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs.Methods and findingsWe investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.ConclusionsWe demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.Trial registrationClinicalTrials.gov Identifier: NCT02811835, NCT01331668.

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Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.

Publications

Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.

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