This commentary refers to ‘Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials’, by M. Galli et al., https://doi.org/10.1093/eurheartj/ehab836 and the discussion piece ‘Are there other factors that influence the assessment of bleeding risk comparing potent P2Y12 inhibitors with clopidogrel?’, by C. Xie et al., https://doi.org/10.1093/eurheartj/ehac598.We thank Xie et al. for their interest in our network meta-analysis (MA) of 15 randomized controlled trials (RCTs) showing that, compared with routine selection of oral potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection (i.e. platelet function or genetic testing) of P2Y12 inhibiting therapy represents the most favourable strategy in terms of safety and efficacy outcomes in patients with acute coronary syndrome.1 The authors raise two comments on our study findings. First, they underline the fact that bleeding definitions varied amongst trials and proposed to run a sensitivity analysis according to the bleeding definition used. We agree that homogeneity in outcome definitions is important. However, with regards to bleeding, a large variety of definitions have been implemented over years, making it challenging to be consistent.2 This is particularly the case when the total number of included trials is high (n = 15) and when multiple definitions are often reported in the same trial. With the aim of providing a rigorous selection of bleeding definition and reducing as much as possible heterogeneity, we have used the bleeding definition as reported in each trial, but we prioritized the definition to be used according to the recommendations of recent consensus, with Bleeding Academic Research Consortium (BARC) being the definition of choice.3
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