Background
For patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the efficacy and safety of novel P2Y
12 antagonists, relative to clopidogrel, remains unclear when either is combined with aspirin and glycoprotein IIb/IIIa inhibitor (GPI). Some randomized controlled trials (RCTs) have compared the newer P2Y
12 antagonists and clopidogrel-based triple-antiplatelet treatment (TAPT) for these patients [
1‐
7]. However, the results have been inconsistent, perhaps due to variations in sample sizes.
The present meta-analysis evaluated the efficacy and safety of the P2Y12 antagonists prasugrel or ticagrelor, relative to that of clopidogrel-based TAPTs, in patients with STEMI undergoing PCI. In particular, the associated rates of acute and long-term adverse events were investigated, including blood flow after PCI, bleeding events, and major adverse cardiovascular events (MACEs).
Discussion
By pooling the results of all available RCTs, we found that a prasugrel- or ticagrelor-based TAPT did not significantly affect the achievement of TIMI grade 3 flow after PCI, or rates of bleeding events, compared with the clopidogrel-based TAPT in patients with STEMI undergoing primary PCI. However, during follow-up significantly less risk of MACE was associated with the prasugrel- or ticagrelor-based TAPT compared with the clopidogrel-based TAPT. Results of subgroup analyses confirmed that the observed benefits of prasugrel- or ticagrelor-based TAPT on clinical outcomes were mainly due to the reduced incidence of 1-year MACE in these groups. Taken together, these results suggest that, for patients with STEMI undergoing PCI, TAPT with prasugrel or ticagrelor in combination with aspirin and GPI may significantly reduce the risk of MACE without increasing the risk of bleeding events, compared with the classic clopidogrel-based TAPT. Our results support the use of the P2Y12 antiplatelet medications ticagrelor or prasugrel over that of clopidogrel-based TAPT for STEMI patients undergoing PCI.
The comparative efficacy and safety of the newer P2Y
12 antiplatelet medications and clopidogrel for patients with coronary heart disease have been evaluated previously in a few meta-analyses. An early meta-analysis comprising 12 RCTs suggested that oral P2Y
12 inhibitors significantly reduced the rate of ischemic events (OR = 0.85) without significantly increasing major bleeding in patients with coronary heart disease, and the risk/benefit ratio was particularly favorable for STEMI patients (OR = 0.77) [
13]. For patients with non-ST segment elevation acute coronary syndrome, results of a subsequent meta-analysis of 4 RCTs indicated that a novel P2Y
12 antiplatelet was associated with a significantly reduced rate of MACE compared with clopidogrel (risk ratio [RR] = 0.87), but the incidences of major and minor bleeding events were significantly higher (RR = 1.27, 1.20) [
14]. For patients with STEMI, results of 3 meta-analyses of RCTs consistently indicated that prasugrel and ticagrelor were more efficacious than clopidogrel for reducing the risk of MACE, although the rates of bleeding events were similar [
15‐
17].
To our best knowledge, none of the above meta-analyses considered the safety and efficacy of novel P2Y
12 antiplatelet medication-based TAPT. Since use of GPI has proved effective to reduce the number of acute coronary no-reflow and stent thrombosis events, the efficacy of novel P2Y
12 antiplatelet medication-based TAPTs deserves evaluation in high-risk patients with STEMI undergoing PCI. Moreover, use of novel P2Y
12 antiplatelet medication-based TAPTs may expose patients to higher risk of bleeding events, and therefore the safety of the above regimens compared with conventional clopidogrel-based TAPT is of particular importance. Our results indicate that for patients with STEMI undergoing PCI, TAPT with prasugrel or ticagrelor in combination with aspirin and GPI may significantly reduce the risk of MACE without increasing the risk of bleeding events, as compared with the classic clopidogrel-based TAPT. This suggests that use of novel P2Y
12 antiplatelet medication-based TAPTs may be favorable for high-risk patients with STEMI undergoing PCI. These beneficial effects of novel P2Y
12 antiplatelet medication-based TAPTs on clinical outcomes in patients with STEMI undergoing PCI may be explained by the potential pharmacological advantages of prasugrel or ticagrelor that have been confirmed in previous studies [
18,
19]. However, whether other mechanisms are involved should be investigated.
Regarding the relative efficacies of prasugrel and ticagrelor-based antiplatelet regimens for patients with STEMI undergoing PCI, results of previous findings may provide some evidence. Serebruany et al. [
17] found that prasugrel, but not ticagrelor, offers a significant 30-day mortality benefit over clopidogrel in PCI-treated STEMI patients. This was confirmed by a subsequent meta-analysis, which showed that for STEMI patients undergoing PCI, prasugrel was superior to ticagrelor, particularly in conjunction with bivalirudin and drug-eluting stents [
15]. Direct evidence was presented in a recently published meta-analysis of head-to-head RCTs, in which prasugrel appeared equivalent or superior to ticagrelor for patients with acute coronary syndrome undergoing PCI at the 30-day follow-up [
20]. However, whether prasugrel based-TAPTs are superior to ticagrelor based-TAPTs in STEMI patients undergoing PCI remains to be determined.
Our study has limitations which should be considered when interpreting the results. Firstly, the number of studies included in the meta-analysis was small. In this study, STEMI patients with atrial fibrillation were not included because no relevant data was reported. Therefore, results of the current analysis could not be extrapolated to this particular population. The conclusions should be confirmed in a large RCT with adequate sample size and follow-up duration. Secondly, the patients’ characteristics, coronary lesions, PCI features, and doses of perioperative medications varied among the RCTs, and we did not have access to the individual patient data. This made it difficult to perform subgroup analyses to evaluate whether differences in these study characteristics could significantly affect the outcome. Finally, although visual inspection did not support significant publication bias of the meta-analysis, quantitative analyses could not be conducted due to the limited number of studies.
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