Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients

Abstract

Objective:

To examine the effect of concomitant use of clopidogrel and PPIs in a national sample of elderly Medicare beneficiaries (age ≥65 years).

Methods:

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).

Results:

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).

Conclusions:

Concomitant use of clopidogrel and PPIs was associated with a slightly increased risk of all-cause mortality but not MCEs.

Keywords::

• Clopidogrel
• Drug
• drug interaction
• Elderly
• Medicare
• Proton pump inhibitors

Transparency

Declaration of funding

This study was sponsored by the Centers for Medicare and Medicaid Services (CMS).

Declaration of financial/other relationships

R.K.M., Y.Y., M.V.D., J.P.B., M.W.S., B.F.B., and K.D.N. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

This study was conducted as part of a project titled ‘Using Medicare/Medicaid Claims Data to Support Medication Outcomes and Pharmacovigilance Research’, which was supported by grant award 1COCMS330731/01 from the Office of Research, Development and Information, CMS.

Previous presentation: This work was presented at the International Society for Pharmacoeconomics and Outcomes Research 17th Annual International Meeting, 2–6 June 2012, Washington, DC, USA.

Notes

*Plavix is a registered trade name of Sanofi-Aventis, NJ, USA.