Guidelines Clinical Practice
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World J Cardiol. May 26, 2011; 3(5): 153-164
Published online May 26, 2011. doi: 10.4330/wjc.v3.i5.153
Clinical evidence of interaction between clopidogrel and proton pump inhibitors
Shoa-Lin Lin, Hui-Min Chang, Chun-Peng Liu, Li-Ping Chou, Jaw-Wen Chan
Shoa-Lin Lin, Chun-Peng Liu, Division of Cardiology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
Hui-Min Chang, Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan
Li-Ping Chou, Division of Cardiology, Sinlau Christian Hospital, Tainan 701, Taiwan
Jaw-Wen Chan, Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan
Author contributions: Lin SL and Chan JW developed the plan of the article and were the primary writers; Liu CP and Chou LP contributed to the development and editing of the manuscript; Chang HM assisted in data collection and writing the Tables of this article.
Supported by (in part) The Kaohsiung Veterans General Hospital, Grant No. VGHKS98-034
Correspondence to: Shoa-Lin Lin, MD, Division of Cardiology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, No. 386, Dar-Chung First Road, Kaohsiung 813, Taiwan. lingoodman@yahoo.com.tw
Telephone: +886-73468278 Fax: +886-73505220
Received: September 29, 2010
Revised: March 16, 2011
Accepted: March 23, 2011
Published online: May 26, 2011
Abstract

Clopidogrel is approved for reduction of atherothrombotic events in patients with cardiovascular (CV) and cerebrovascular disease. Dual antiplatelet therapy with aspirin and clopidogrel decreases the risk of major adverse cardiac events after acute coronary syndrome or percutaneous coronary intervention, compared with aspirin alone. Due to concern about gastrointestinal bleeding in patients who are receiving clopidogrel and aspirin therapy, current guidelines recommend combined use of a proton pump inhibitor (PPI) to decrease the risk of bleeding. Data from previous pharmacological studies have shown that PPIs, which are extensively metabolized by the cytochrome system, may decrease the ADP-induced platelet aggregation of clopidogrel. Results from retrospective cohort studies have shown a higher incidence of major CV events in patients receiving both clopidogrel and PPIs than in those without PPIs. However, other retrospective analyses of randomized clinical trials have not shown that the concomitant PPI administration is associated with increased CV events among clopidogrel users. These controversial results suggest that large specific studies are needed. This article reviews the metabolism of clopidogrel and PPIs, existing clinical data regarding the interaction between clopidogrel and PPIs, and tries to provide recommendations for health care professionals.

Keywords: Antiplatelet therapy; Aspirin; Clopidogrel; Proton pump inhibitor