The mortality benefit seen with the newer more potent oral P2Y12 inhibitors prasugrel and ticagrelor over clopidogrel is dependent on the underlying risk: A class effect as suggested by a meta-regression analysis

Abstract

BackgroundThe two newer oral P2Y12 inhibitors prasugrel and ticagrelor have proven superior to clopidogrel in the treatment of acute coronary syndrome (ACS). The extent to which the reduction in mortality seen with ticagrelor is confined to this particular agent is hard to judge by simply looking at the overall study results as the study populations were composed of different cohorts at substantially different risk of death. MethodsA meta-regression technique was applied to 12 distinctive patient cohorts, six for each of prasugrel and ticagrelor, to investigate differential effects on mortality of P2Y12 inhibitors. ResultsData for the analysis cohorts, totalling 37,372 patients, were extracted from publications and cover a widely comparable spectrum of patient types, defined by the type of ACS and treatment strategy. The meta-regression lines for cardiovascular mortality with prasugrel or ticagrelor (each versus clopidogrel), as well as for both agents pooled, indicate a linear relationship with increasing benefit seen with higher underlying risk (p=0.007, 0.021 and 0.003, and R2=0.87, 0.77 and 0.62, respectively). ConclusionsIn the ACS patients studied, we found a mortality benefit with the two newer oral P2Y12 inhibitors prasugrel and ticagrelor when compared with clopidogrel, which increases progressively as the underlying risk of death increases. This appears to be a class effect for these two newer agents.