Per‐Protocol Versus Intention‐to‐Treat in Clinical Trials: The Example of GLOBAL‐LEADERS Trial

Abstract

fter drug- eluting stent implantation, the classic therapy was dual antiplatelet therapy (DAPT) for 1 year and then stopping P2Y12 inhibitor while maintaining aspirin forever. The main limitation is the in-creased risk of bleeding with prolonged DAPT strategy might offset the ischemic benefit. Given that ischemic risk is higher in the initial phase whereas bleeding risk is maintained in the long term, deescalation therapies have been proposed, either with shorter DAPT durations or with aspirin- free strategies. 1 In fact, DAPT should follow the Goldilocks principle 2 (not too short, not too long). Recent studies (GLOBAL- LEADERS, 3 TWILIGHT [Ticagrelor with Aspirin or Alone in High- Risk Patients after Coronary Intervention], 4 TICO [Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus- Eluting Stent for Acute Coronary Syndrome], 5 STOP- DAPT [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus- Eluting Cobalt-Chromium Stent], 6 SMART- CHOICE [Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Anti- platelet Therapy in Patients Undergoing Implantation of Coronary Drug- Eluting Stents] 7 ) suggest that the deescalation strategy with an abbreviated DAPT period after percutaneous coronary intervention (1– 3 months) followed by aspirin cessation and P2Y12 inhibitor monotherapy mitigates bleeding risk without losing efficacy for ischemic prevention. Among all these trials, GLOBAL- LEADERS 3 offers the largest sample size and is the only one designed as a superiority trial.