Efficacy and safety of potent p2y12 inhibitors versus clopidogrel in complex percutaneous coronary intervention: a systematic review and meta-analysis

Background Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after percutaneous coronary intervention (PCI) to reduce the risk of adverse cardiovascular events. Currently, an increasing number of PCIs are performed in patients with complex anatomic features, which is associated with a higher risk of ischemic events. Potent P2Y12 inhibitors such as prasugrel and ticagrelor provide more rapid, uniform and potent platelet inhibition than clopidogrel. However, the balance between enhanced antithrombotic efficacy and the potential increase in bleeding risk with potent P2Y12 inhibitors in the setting of complex PCI remains uncertain. Purpose This systematic review and meta-analysis aimed to assess the effectiveness and safety of DAPT strategies using potent P2Y12 inhibitors (prasugrel or ticagrelor) versus clopidogrel in patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) undergoing complex PCI. Methods PubMed, Scopus and Cochrane databases were searched for randomized controlled trials (RCTs) and observational studies comparing ticagrelor or prasugrel versus clopidogrel in patients undergoing complex PCI. Complex PCI was defined according to criteria commonly used in the literature, including coronary bifurcations, chronic total occlusions, severe calcifications requiring atherectomy and left main disease. All outcomes were assessed at the 1-year follow-up. We pooled risk ratios (RR) with 95% confidence intervals (CI) using a random-effects model. Heterogeneity was assessed using the I² statistic. Results We included one randomized controlled trial and nine observational studies, encompassing a total of 37,365 patients undergoing complex PCI. Among these, 11,078 received dual antiplatelet therapy with potent P2Y12 inhibitors (8,450 with ticagrelor and 2,628 with prasugrel), while 26,287 patients were treated with clopidogrel-based DAPT. Treatment with potent P2Y12 inhibitors was associated with significantly lower all-cause mortality (RR 0.52; 95% CI 0.36–0.76; p=0.0007) and cardiovascular death (RR 0.61; 95% CI 0.48–0.78; p<0.0001) compared to clopidogrel. No significant differences were observed between groups in the incidence of myocardial infarction (RR 0.80; 95% CI 0.58–1.10; p=0.17), stroke (RR 0.71; 95% CI 0.33–1.53; p=0.38), target vessel revascularization (RR 0.86; 95% CI 0.58–1.26; p=0.44) and stent thrombosis (RR 0.70; 95% CI 0.43–1.15; p=0.16). The risk of major bleeding did not differ significantly between the treatment groups (RR 0.93; 95% CI 0.71–1.20; p=0.57). Conclusion In patients undergoing complex PCI, DAPT with potent P2Y12 inhibitors was associated with a significant reduction in all-cause mortality and cardiovascular death, without an increased risk of major bleeding.ALL- CAUSE MORTALITY AND C.V. DEATH MYOCARDIAL INFARCTION AND MAJOR BLEEDING