Single versus Dual Antiplatelet Therapy in Patients with Severe Peripheral Arterial Disease Undergoing TAVI: Insights from The Hostile Registry

Aims: Single antiplatelet therapy (SAPT) has been shown to be a safer alternative to dual antiplatelet therapy (DAPT) in patients without atrial fibrillation undergoing transcatheter aortic valve implantation (TAVI). However, antithrombotic therapy for TAVI patients with severe peripheral artery disease (PAD) remains an underexplored area. This study aimed to evaluate and compare the outcomes of SAPT and DAPT in this high-risk patient population. Methods and results: The HOSTILE registry was a multicenter, international, observational study including 1,707 consecutive patients with hostile femoral access undergoing TAVI in 28 international centers. Among 573 patients without atrial fibrillation treated through transfemoral or non-thoracic alternative approach, 144 received SAPT and 429 DAPT after TAVI. The primary efficacy endpoint was the propensity-adjusted rate of major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, stroke or transient ischemic attack. The primary safety endpoint was the propensity-adjusted rate of major bleeding. Outcomes were reported at 30 days and 12 months. DAPT was associated with a non-significant reduction in MACE at 30 days (HR 0.74, 95% CI 0.25-2.18; p=0.59) and at 12 months (HR 0.89, 95% CI 0.35-2.24; p=0.80) compared to SAPT, but with a significant interaction between antiplatelet strategy and PAD severity (p=0.01), suggesting a greater benefit of DAPT in patients with a high PAD severity. DAPT was associated with reduced all-cause death at 12 months (HR 0.22, 95% CI 0.10-0.47; p<0.001) but not at 30 days (HR 0.26, 95% CI 0.05-1.22; p=0.09) compared with SAPT. There was no difference in major bleeding at 30 days (p=0.13) or 12 months (p=0.10) between groups. There were no differences between groups in any bleeding at 30 days (p=0.16) or 12 months (p=0.17). Conclusions: In TAVI patients with severe PAD, DAPT was associated with a trend toward improved outcomes compared with SAPT, particularly in those with higher PAD severity. These findings, including the observed reduction in 1-year mortality with DAPT, warrant further investigation in prospective studies.