Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes.

Background: Clopidogrel is beneficial after ACS. Recent data suggest the superiority of prasugrel or ticagrelor compared with clopidogrel. However, there is no comparison of prasugrel vs. ticagrelor. We performed an adjusted indirect meta-analysis comparing prasugrel vs. ticagrelor for acute coronary syndromes (ACSs).

Methods: Randomized trials were searched in PubMed. The primary end-point was the composite of death, myocardial infarction (MI) or stroke. Odds ratios (OR) were computed (95% confidence intervals).

Results: Three trial (32,893) patients were included. Overall, either prasugrel or ticagrelor appeared significantly superior to clopidogrel for the 12-month risk of death, MI or stroke (OR=0.83 [0.77-0.89], p<0.001), death (OR=0.83 [0.74-0.93], p=0.001), MI (OR=0.79 [0.73-0.86], p<0.001), and stent thrombosis (OR=0.61 [0.51-0.74], p<0.001), without any significant difference in stroke or major bleeding (both p>0.05), despite more frequent drug discontinuation (OR=1.12 [1.05-1.19], p<0.001). Head-to-head comparison of prasugrel vs. ticagrelor showed no significant differences in overall death, MI, stroke, or their composite (all p>0.05). Prasugrel was associated with a significantly lower risk of stent thrombosis (OR=0.64 [0.43-0.93], p=0.020). Ticagrelor was associated with a significantly lower risk of any major bleeding (OR=1.43 [1.10-1.85], p=0.007), and major bleeding associated with bypass grafting (OR=4.30 [1.73-10.6], p=0.002). However, the more clinically relevant risk of major bleeding not related to bypass surgery was similar with either prasugrel or ticagrelor (OR=1.06 [0.77-1.45], p=0.34).

Conclusions: Prasugrel and ticagrelor are superior to clopidogrel for ACS. Head-to-head comparison suggests similar efficacy and safety of prasugrel and ticagrelor, but prasugrel appears more protective from stent thrombosis, while causing more bleedings.