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.

Declarations

Disclosure of Interest

All authors declare no disclosure of interest for this contribution.

References