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)?

Methods:

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.

Results:

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.

Conclusions:

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.

Perspective:

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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