Efficacy and safety analysis of new P2Y₁₂ inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Abstract

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p < 0.0001), MACEs (OR 0.81; 95% CI 0.73–0.90, p < 0.0001), stent thrombosis (OR 0.58; 95% CI 0.49–0.69, p < 0.00001), myocardial infarctions (OR 0.87; 95% CI 0.76–0.99, p = 0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p = 0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p = 0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p = 0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.

Keywords: :

• Acute coronary syndrome
• Clopidogrel
• Meta-analysis
• New P2Y₁₂ inhibitors
• Percutaneous coronary intervention
• Randomized clinical trial

Transparency

Declaration of funding

This study had no commercial funding. This study was supported by the National Science Foundation of China (No 81200220) and the Science Foundation of Hubei Province (No 2014CDFB480).

All authors planned the study and contributed to the interpretation of the data and revisions, and provided inputs at all stages of the study. All the authors have approved the final version of the manuscript.

Declaration of financial/other relationships

X.-D.G., B.-Z.W., D.F., Q.F., K.-Y.L., S.-L.-Y.D., S.P., and J.W. 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 on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to thank Dr Amit Bhat and Mrs Nishi Gupta (Indegene Lifesystems Pvt Ltd, Bangalore, India), for providing medical writing support and technical assistance in the preparation of this manuscript.