Clinical impact of early clopidogrel discontinuation following acute myocardial infarction hospitalization or stent implantation: analysis in a single integrated health network

ABSTRACT

Objective: To determine the association between the discontinuation of clopidogrel therapy prior to 1 year and the risk of acute myocardial infarction (AMI) hospitalization, coronary intervention or all-cause mortality in a cohort of managed-care patients following AMI hospitalization or stent insertion.

Research design and methods: This observational cohort study included 1152 patients enrolled in the Health Alliance Plan who were hospitalized for AMI, or who underwent coronary stent placement. Clopidogrel use was assessed using pharmacy claims data. The association between discontinuation of clopidogrel prior to 1 year following the initial ACS event and the primary outcome of AMI hospitalization/procedure was assessed using Cox proportional hazards models. Additionally, an analysis was conducted to determine the association of discontinuation prior to 1 year with a secondary composite outcome of AMI hospitalization/coronary stent procedure or all-cause mortality.

Main outcome measures: The primary outcome was AMI hospitalization or procedure. The secondary outcome was a composite of AMI hospitalization/ procedure, or all-cause mortality.

Results: Discontinuation of clopidogrel in the total cohort of patients was associated with a significantly higher risk of the primary outcome of AMI hospitalization/ coronary intervention (HR 2.712, 95% CI 1.634–4.502). Consistent with this finding, discontinuation of clopidogrel was also associated with a significantly higher risk of the secondary composite endpoint (HR 1.844, 95% CI 1.281–2.653).

Conclusions: In patients enrolled in an integrated health network, clopidogrel discontinuation prior to 1 year following AMI hospitalization or stent placement is associated with adverse outcomes including greater risk of death, AMI hospitalization or coronary intervention. These results should be interpreted within the context and limitations of observational research, which cannot attribute causality.

Keywords: :

• Acute coronary syndrome
• Clopidogrel
• Myocardial infarction
• Stent

Transparency

Declaration of funding

Sanofi-aventis and Bristol-Myers Squibb funded this research as well as the agency of the professional medical writers who authored this paper.

Declaration of financial/other relationships

D.W., K.B., R.C., and L.S. have disclosed that they are employed by Analytica International which received funding from sanofi-aventis and Bristol-Myers Squibb. D.M. has disclosed that she is employed by Bristol-Myers Squibb. E.M. has disclosed that he is employed by sanofi-aventis. L.L. has disclosed that she is employed by Henry Ford Health System and has received study funding from Analytica and research funding from the National Cancer Institute, Department of Defense, Centers for Disease Control, American Cancer Society, GlaxoSmithKline, and Policy Analysis Incorporated. J.S. has disclosed that he has received study funding from Kaleida Foundation, Bristol-Myers Squibb/sanofi-aventis and research funding from numerous pharmaceutical companies. He has also served as a consultant for sanofi-aventis and on the speakers’ bureau of Abbott, AstraZeneca, GlaxoSmithKline and sanofi-aventis.

All peer reviewers receive honoraria from CMRO for their review work. Peer reviewer 1 has disclosed that he/she has received a grant for Accumetrics sponsoring the GRAVITAS (Gauging Responsiveness with a Verify Now Assay – Impact on Thrombosis and Safety) clinical trial which uses clopidogrel. The other peer reviewer has disclosed that he/she has no relevant financial relationships.

Acknowledgment

Editorial assistance was provided by Jacob M. Willet, MPH, Analytica International, New York, NY, USA.

These data were accepted for presentation in part at the 2009 American College of Cardiology Annual Meeting, March 28, Orlando, FL, USA.