De-escalation of dual antiplatelet therapy (DAPT) is a strategy used to improve outcomes after percutaneous coronary intervention (PCI).¹˒² However, the impact of patient sex on the safety and efficacy of these strategies has been unclear. A new network meta-analysis published in the European Heart Journal has investigated these potential differences.¹

Methodology

The study analysed data from 20 randomised controlled trials, encompassing 71,272 patients who underwent PCI and did not have a baseline indication for oral anticoagulation. Of these, 23.3% were female. De-escalated DAPT regimens were compared against standard DAPT. The de-escalation strategies were categorised as either DAPT discontinuation (stopping aspirin or the P2Y12 inhibitor) or a P2Y12 inhibitor switch or dose reduction. The co-primary endpoints were trial-defined major adverse cardiovascular events (MACE) and major bleeding.

Results

The analysis revealed a significant interaction between treatment effect and sex for DAPT discontinuation strategies. In females, DAPT discontinuation was associated with a reduction in MACE (HR, 0.86; 95% CI, 0.75–0.98) but had no significant effect on major bleeding (HR, 1.04; 95% CI, 0.76–1.43) compared to standard DAPT. Conversely, in males, this strategy reduced major bleeding (HR, 0.60; 95% CI, 0.44–0.82) but did not reduce MACE (HR, 1.04; 95% CI 0.93–1.16).

For strategies involving a P2Y12 inhibitor switch or dose reduction, no significant interaction by sex was observed for either MACE or major bleeding. In treatment ranking, aspirin discontinuation was identified as the best strategy for most outcomes in females. For males, a P2Y12 inhibitor switch to clopidogrel was associated with the best outcomes.

In Practice

The findings suggest that the choice of DAPT de-escalation strategy may need to be tailored based on patient sex. The study authors concluded, "Sex may influence the safety and efficacy of antiplatelet de-escalation strategies after PCI, particularly those involving the shortening of DAPT. Aspirin discontinuation may represent the optimal strategy for females, while P2Y12 inhibitor switch to clopidogrel may be most effective for males."¹

References

1. Occhipinti G, Laudani C, Galli M, et al. Sex differences in dual antiplatelet therapy de-escalation strategies after percutaneous coronary intervention: a network meta-analysis. Eur Heart J. 2026;47(16):1901–1913. https://doi.org/10.1093/eurheartj/ehaf473

2. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826. https://doi.org/10.1093/eurheartj/ehad191

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