Dataset Information

Pharmacodynamic impacts of proton pump inhibitors on the efficacy of clopidogrel in vivo--a systematic review.

ABSTRACT:

Background

There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute coronary syndrome. Most pharmacokinetic and pharmacodynamic studies in vivo were conducted using small sample sizes and were single centered, resulting in conflicting data.

Hypothesis

PPIs may attenuate the antiplatelet effect of clopidogrel in vivo and lead to an increased risk of cardiovascular events.

Methods

PubMed, the Cochrane Library, Embase, Web of Science, and China Biology Medicine Disc were searched. Randomized controlled trials that compared pharmacodynamic impacts of a PPI on the efficacy of clopidogrel in vivo were included. Two independent reviewers evaluated study quality and extracted data for meta-analysis.

Results

We identified 8 eligible studies. Compared to clopidogrel treatment alone, patients who received both a PPI and clopidogrel had less of a decrease in the platelet reactivity index (weighted mean difference [WMD]: 8.18; 95% confidence interval [CI]: 6.81-9.56; P<0.00001), less adenosine 5'-diphosphate-induced platelet aggregation inhibition (WMD: 7.28; 95% CI: 2.44-12.11; P=0.003), higher P2Y12 reaction units (WMD: 40.58; 95% CI: 19.31-61.86; P=0.0002), and higher risks of clopidogrel resistance (odds ratio [OR]: 2.49; 95% CI: 1.49-4.14; P=0.0005). There were no significant differences, however, for the incidences of major adverse cardiovascular events between the 2 groups (OR: 1.07; 95% CI: 0.44-2.59; P=0.88), and treatment with a PPI and clopidogrel significantly reduced the risk of adverse gastrointestinal events (OR: 0.16; 95% CI: 0.04-0.62; P=0.008).

Conclusions

Concomitant use of a PPI with clopidogrel attenuated the antiplatelet effect of clopidogrel, but may be clinically unimportant because there were no clinical differences in the risk for major adverse cardiovascular events.

SUBMITTER: Chen J

PROVIDER: S-EPMC6649507 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

Pharmacodynamic impacts of proton pump inhibitors on the efficacy of clopidogrel in vivo--a systematic review.

Chen Jie J Chen Shi-yao SY Lian Jing-jing JJ Zeng Xiao-qing XQ Luo Tian-cheng TC

Clinical cardiology 20130228 4

<h4>Background</h4>There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute coronary syndrome. Most pharmacokinetic and pharmacodynamic studies in vivo were conducted using small sample sizes and were single centered, resulting in conflicting data.<h4>Hypothesis</h4>PPIs may attenuate the antiplatelet effect of clopidogrel in vivo and lead to an increased risk of cardiovascular events ...[more]

PMID: 23450832

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Project description: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.

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.

Dataset Information

Pharmacodynamic impacts of proton pump inhibitors on the efficacy of clopidogrel in vivo--a systematic review.

Background

Hypothesis

Methods

Results

Conclusions

Publications

Pharmacodynamic impacts of proton pump inhibitors on the efficacy of clopidogrel in vivo--a systematic review.

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