Coronary Artery Disease
Meta-Analysis of the Relative Efficacy and Safety of Oral P2Y12 Inhibitors in Patients With Acute Coronary Syndrome

https://doi.org/10.1016/j.amjcard.2017.03.011Get rights and content

A cornerstone of medical therapy for patients with acute coronary syndrome (ACS) is dual antiplatelet therapy, which includes aspirin and a P2Y12 inhibitor. Randomized controlled trials (RCTs) have shown that prasugrel and ticagrelor are superior to clopidogrel, but none directly compared these 3 commonly used oral P2Y12 inhibitors for safety and efficacy. Therefore, we performed a Bayesian network meta-analysis of RCTs to compare the efficacies and safeties of 3 commonly used oral P2Y12 inhibitors in patients with ACS. Scientific databases and websites were searched for relevant RCTs. We included data from 9 RCTs that enrolled 106,288 patients. Clopidogrel decreased the rates of major adverse cardiac event, recurrent myocardial infarction, and all-cause mortality compared with placebo. Both ticagrelor and prasugrel decreased the rates for major adverse cardiac event and recurrent myocardial infarction compared with clopidogrel, but there was no difference between the 2. Both also decreased the stent thrombosis rate compared with clopidogrel, but prasugrel was more effective than ticagrelor. Ticagrelor use was also associated with improved all-cause and CV mortalities compared with clopidogrel. There was no difference in CV mortality or all-cause mortality between clopidogrel and prasugrel. Prasugrel use was also associated with significantly increased risk of major bleeding compared with clopidogrel but showed a nonsignificant trend toward increasing the risk of bleeding compared with ticagrelor. In treatment ranking, ticagrelor was the most efficacious, and prasugrel was the least safe. In conclusion, this meta-analysis shows that in patients with ACS, adding P2Y12 inhibitors to aspirin and other standard treatments reduces ischemic events and all-cause mortality. Among the commonly used oral P2Y12 inhibitors, ticagrelor has the best net efficacy and safety profile.

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Methods

This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses.7 We performed a systematic search of PubMed, Embase, and the Cochrane Library and cross-referenced relevant articles using various combinations of keywords, such as “acute coronary syndrome,” “myocardial infarction,” “P2Y12 inhibitors,” “thienopyridines,” “clopidogrel,” “prasugrel,” and “ticagrelor,” for eligible published

Results

Nine RCTs that included 106,288 patients met our criteria for inclusion.4, 5, 12, 13, 14, 15, 16, 17, 18 The search flow diagram is shown in Supplementary Figure 1. The network of treatment comparisons is shown in Figure 1. The bias assessment for each RCT is shown in Supplementary Figure 2. All included studies are high-quality trials based on Cochrane Collaboration guidelines (Supplementary Figure 2).

Table 1 describes the characteristics of the individual trials. Those trials enrolled a broad

Discussion

In this study of 106,288 patients enrolled in 9 RCTs, we compared the relative efficacies and safeties of 3 commonly used oral P2Y12 inhibitors across a broad spectrum of patients with ACS using Bayesian network meta-analysis. This is the most comprehensive meta-analysis of RCTs and included the largest number of patients reported on this topic. We found that clopidogrel decreased the risks of MACEs and recurrent MI at the expense of an increased risk of major bleeding. However, overall, the

Disclosures

The authors have no conflicts of interest to disclose.

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