Ticagrelor for Secondary Prevention of CVD

Study Questions:

What is the safety and efficacy of long-term ticagrelor among patients with multivessel coronary artery disease (CAD) and prior myocardial infarction (MI)?


This was a prespecified analysis of patients with multivessel CAD from 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. The trial enrolled patients who had a prior history of MI with one additional risk factor for cardiovascular disease (CVD). Patients were randomized to ticagrelor plus aspirin versus placebo plus aspirin and followed for a median of 33 months. Multivessel CAD was defined as >50% stenosis in >2 separate major coronary territories at the time of the index event. Major adverse cardiac events (MACE) consisted of cardiovascular death, MI, or stroke, and coronary events were defined as coronary-related death, MI, or definite stent thrombosis. The primary safety endpoint was TIMI (Thrombolysis in Myocardial Infarction) major bleeding.


Of the 21,162 patients in the PEGASUS-TIMI 54 trial, 12,558 (59%) had multivessel CAD. Ticagrelor reduced MACE (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.72-0.94) and coronary events (HR, 0.76; 95% CI, 0.66-0.88) in patients with multivessel CAD compared to placebo. There was a 36% reduction in coronary death (HR, 0.64; 95% CI, 0.48-0.85), a 21% reduction in MI (HR, 0.79; 95% CI, 0.67-0.93), and a 41% reduction in definite stent thrombosis (HR, 0.59; 95% CI, 0.37-0.94) with the 90 mg dose. There was an associated hazard of TIMI major bleeding with ticagrelor (HR, 2.67; 95% CI, 1.81-3.93), but no significant difference in intracranial or fatal bleeding (0.67% vs. 0.63%; adjusted HR, 1.21; 95% CI, 0.69-2.12). Sixty patients with multivessel CAD need to be treated with ticagrelor for 3 years to prevent one event.


Among patients with a prior MI, CVD risk factors, and multivessel CAD, addition of ticagrelor therapy is associated with a significant reduction in major CV events including coronary heart disease–related death.


In this predominantly male cohort of patients, presence of multivessel CAD is associated with increased risk for MACE and coronary events. Prolonged use of ticagrelor with aspirin is associated with a significant reduction in major CV events including a 46% reduction in coronary death. This effect is more pronounced among patients with multivessel CAD. The benefit comes with increased risk of major bleeding, but not fatal or intracranial bleeding. Long-term ticagrelor can be considered part of medical therapy for secondary prevention of CVD among patients with multivessel CAD after bleeding risk has been considered.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Interventions and ACS, Interventions and Coronary Artery Disease

Keywords: Aspirin, Acute Coronary Syndrome, Coronary Artery Disease, Constriction, Pathologic, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Purinergic P2Y Receptor Antagonists, Risk Factors, Secondary Prevention, Stents, Stroke, Thrombosis

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