Long-Term Ticagrelor in Patients With Prior Coronary Stenting in the PEGASUS-TIMI 54 Trial.

Abstract

Background Coronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long-term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial. Methods and Results Patients in PEGASUS-TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug-eluting stent and first- versus later-generation drug-eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelorpooled reduced major adverse cardiovascular events (7.0% versus 8.0%; hazard ratio [HR], 0.85; 95% CI, 0.75-96) regardless of stent type (bare metal stent versus drug-eluting stent: pinteraction=0.767; first versus later generation: pinteraction=0.940). The rate of any stent thrombosis was numerically lower with ticagrelorpooled (0.7% versus 0.9%; HR, 0.73; 95% CI, 0.50-1.05) and Thrombolysis in Myocardial Infarction major bleeding was increased (HR, 2.65; 95% CI, 1.90-3.68). Conclusions Long-term ticagrelor reduces major adverse cardiovascular events in patients with prior myocardial infarction and coronary stenting regardless of stent type, with the benefit driven predominantly by reduction in de novo events. Nonfatal major bleeding is increased with ticagrelor. Registration Information clinicaltrials.gov. Identifier: NCT01225562.

• Authors: Brian A Bergmark, Deepak L Bhatt, P Gabriel Steg, Andrzej Budaj, Robert F Storey, Yared Gurmu, Julia F Kuder, KyungAh Im, Giulia Magnani, Ton Oude Ophuis, Christian Hamm, Jindřich Špinar, Robert G Kiss, Frans J Van de Werf, Gilles Montalescot, Per Johanson, Eugene Braunwald, Marc S Sabatine, Marc P Bonaca
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 10 Issue 17 Pg. e020446 (09 07 2021) ISSN: 2047-9980 [Electronic] England
• PMID: 34423649 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Platelet Aggregation Inhibitors
• Ticagrelor

Topics

• Drug Therapy, Combination
• Drug-Eluting Stents
• Hemorrhage (chemically induced, epidemiology)
• Humans
• Myocardial Infarction (drug therapy, prevention & control)
• Percutaneous Coronary Intervention
• Platelet Aggregation Inhibitors (adverse effects, therapeutic use)
• Secondary Prevention
• Stents
• Stroke (drug therapy, etiology, prevention & control)
• Thrombosis (drug therapy, prevention & control)
• Ticagrelor (adverse effects, therapeutic use)
• Treatment Outcome