Net clinical benefit of extended dual pathway inhibition according to baseline risk in patients with chronic coronary syndrome: a COMPASS substudy

Guidelines recommend extended dual pathway inhibition (DPI) with aspirin and rivaroxaban in patients with chronic coronary syndrome (CCS) at high ischaemic risk. The CHADS-P₂A₂RC score improves risk prediction and enables antithrombotic treatment allocation in these patients. This study evaluated the net clinical benefit of DPI treatment according to baseline risk as classified by the CHADS-P₂A₂RC score in patients with CCS included in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial.

COMPASS patients with CCS (n = 14 670), randomized to aspirin alone or DPI, were stratified according to cardiovascular risk using the CHADS-P₂A₂RC score. Endpoints were major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month risk difference of MACE and bleeding. Thirty-month incidences of MACE [7.9% vs. 3.9%, hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.83–2.18] and fatal/critical organ bleeding (1.2% vs. 0.8%, HR 1.49, 95% CI 1.06–1.92) were higher in high-risk (CHADS-P₂A₂RC ≥ 4) than in low/moderate-risk (CHADS-P₂A₂RC < 4) patients. DPI reduced MACE (low/moderate risk: HR 0.62, 95% CI 0.47–0.82; high risk: HR 0.82, 95% CI 0.68–0.99, P for interaction 0.09) and all-cause death (low/moderate risk: HR 0.65, 95% CI 0.46–0.91; high risk: HR 0.81, 95% CI 0.65–1.00, P for interaction 0.29), without substantially increasing fatal/critical organ bleeding (low/moderate risk: HR 1.35, 95% CI 0.72–2.53; high risk: HR 1.18, 95% CI 0.73–1.90, P for interaction 0.73). DPI provided net clinical benefit of similar magnitude in low/moderate-risk (−1.81%, 95% CI −3.00 to −0.62) and high-risk (−1.96%, 95% CI −3.60 to −0.33) CCS patients.

As classified by the CHADS-P₂A₂RC score, low/moderate- and high-risk patients with CCS derived similar net clinical benefit and reduction in all-cause death from DPI treatment.