Incidence of death and recurring acute coronary syndrome after stopping clopidogrel therapy in a large commercially-insured population in the US

Abstract

Background/objective:

Guidelines support clopidogrel therapy in medically-treated or percutaneous coronary intervention (PCI) patients after hospitalization for acute coronary syndrome (ACS). However, clopidogrel discontinuation has been associated with increased short-term risks. This study evaluated the risk of adverse outcomes (AOs), defined as death or recurrent ACS, after clopidogrel discontinuation in a managed-care population.

Methods:

ACS patients (n = 7625) with ≥1 clopidogrel pharmacy claim from 2001 to 2006 and no AO before discontinuing clopidogrel were identified from administrative claims data. AO occurrences were recorded at 90-day intervals following clopidogrel discontinuation.

Results:

The mean (SD) duration of clopidogrel therapy for medically-treated, bare metal stent (BMS) and drug eluting stent (DES) patients was 349.2 (393.1) days, 235.6 (383.0) days, and 280.2 (227.1) days, respectively. Among medically-treated patients, Poisson regression analysis showed a 2.19 times higher AO risk (p < 0.01), a 1.63 times greater risk among BMS patients (p < 0.01), and a 1.56 times greater risk for DES patients (p ≥ 0.05) during days 0–90 versus days 91–180 after clopidogrel discontinuation. Sensitivity analysis showed that medically-treated, BMS and DES patients with ≤90 days of clopidogrel therapy had 2.13, 1.68 and 2.40 times higher AO risk, respectively, during days 0–90 versus 91–180 after discontinuation. No significant elevated AO risk was observed after discontinuation in patients on clopidogrel for 91–270 days. Limitations included those associated with the use of administration claims date, the absence of clinical data and lack of knowledge of aspirin use.

Conclusions:

Patients who discontinued clopidogrel therapy were at high risk of death or recurrent ACS during the first 90 days. AO risks following discontinuation appeared elevated in patients with ≤90 days of clopidogrel therapy versus those with >90 days of treatment.

Key words::

• Acute coronary syndrome
• Adverse outcomes
• Clopidogrel therapy
• Managed care population

Transparency

Declaration of funding

AstraZeneca, LP funded this research.

Declaration of financial/other interests

J.J.S. and M.J.C. have disclosed that they are employed by HealthCore Inc., a company that received funding from AstraZeneca to conduct this study. C.L.C. has disclosed that she was an employee of HealthCore at the time this study was undertaken. G.D.W. has disclosed that she was employed by AstraZeneca at the time this study was conducted, and O.H. has disclosed that he is employed by AstraZeneca LP. 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

The authors would like to thank Bernard Tulsi, who worked on an early draft of this manuscript.

These data were presented in part at the American College of Cardiology (ACC) 58th Annual Scientific Session, Orlando, Florida, March 29–31, 2009.