One or 3 months dual antiplatelet therapy in high bleeding risk patients: splitting hair or aiming at the bullseye?

This commentary refers to ‘Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials’, by F. Costa et al., https://doi.org/10.1093/eurheartj/ehac706 and the discussion piece ‘What is the optimal duration of dual antiplatelet therapy after percutaneous coronary intervention in high bleeding risk: 1 month or 3 months?’, by Y. Zhao et al., https://doi.org/10.1093/eurheartj/ehad728. We appreciate the authors’ interest in our work.1 Whether 1- or 3-month dual antiplatelet therapy (DAPT) is preferable in patients with high bleeding risk (HBR) is not entirely clear. European acute coronary syndrome (ACS) guidelines provide a Class IIb recommendation for 1 month of DAPT exclusively in patients with HBR. In contrast, a Class IIa recommendation is given for 3 months of DAPT followed by P2Y12i monotherapy for both HBR and non-HBR patients.2 Both regimens, compared with longer DAPT courses, have demonstrated a reduction in bleeding with no increase in ischaemic events, but no randomized study directly compared 1 and 3 months DAPT. Using our previously published data, we employed a Bayesian framework network meta-analysis to provide an indirect comparison of 1 vs. 3 months DAPT in patients with HBR.1 We found no significant difference between the two durations for major adverse cardiovascular events [odds ratio (OR) 0.95; 95% confidence interval (CI) 0.49–1.77] and major or clinically relevant non-major bleeding (OR 0.78; 95% CI 0.44–1.50). However, these results should be interpreted with caution due to the wide observed confidence intervals and the inherent limitations of an indirect comparison across studies for which no direct evidence exists. A prior analysis based on the Xience 28 and Xience 90 registries, demonstrated that 1-month compared with 3-month DAPT is associated with reduced major and minor bleeding without an increase in ischaemic events.3 Unlike other secondary prevention strategies after percutaneous coronary intervention (PCI) or ACS, DAPT is associated with bleeding complications that may negatively impact survival.4 Achieving optimal antithrombotic protection without increasing bleeding-related harm is paramount, especially in patients with HBR. Hence, a 1-month DAPT regimen might be the best approach to minimize bleeding risk. One-month DAPT was investigated in the only dedicated HBR study addressing the optimal DAPT duration in patients with HBR, with consistent results in patients with ACS, complex PCI or both.5 Extending treatment to 3 months remains reasonable in selected patients with HBR, given the premises that this regimen has been investigated in a broader patient population, including HBR, with overall consistent results. Yet again, it should be emphasized that no direct evidence currently exists showing that 3-month DAPT is associated with a lower risk of ischaemic events compared with 1-month DAPT, whereas the latter regimen appears to lower bleeding based on observational data.3 Importantly, both 1- or 3-month DAPT durations are to be preferred over longer DAPT courses in patients with HBR. It remains surprising that recent guidelines continue to support 12-month DAPT as the default regimen,2 while a low-class recommendation for shorter treatment in HBR is given despite strong evidence from dedicated randomized clinical trials and meta-analysis.1,5 The 12-month DAPT duration has been initially advocated on a weak evidence base and has progressively become less and less supported by the data. In conclusion, whether 1- or 3-month DAPT is the preferable DAPT duration in patients with HBR remains open to interpretations. Yet, both are to be preferred over the old paradigm of a default 12-month DAPT. Such practice should be abandoned in patients with HBR, in line with the outstanding evidence in favour of a shorter treatment in this population. All authors declare no disclosure of interest for this contribution.