Stent Thrombosis With Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes: An Analysis From the Prospective, Randomized PLATO Trial

Study Questions:

What are the effects of ticagrelor versus clopidogrel on stent thrombosis in the PLATO (Platelet Inhibition and Patient Outcomes) trial?

Methods:

PLATO was an international, randomized, double-blind, double-dummy, event-driven trial in patients hospitalized for acute ST-segment–elevation acute coronary syndrome (ACS) scheduled for a primary percutaneous coronary intervention (PCI) strategy or non–ST-segment–elevation ACS managed invasively or medically. Patients were randomized to receive either ticagrelor or clopidogrel within 24 hours of the onset of cardiac ischemic symptoms and before PCI. Stent thrombosis events were summarized with Kaplan–Meier curves and estimates at 360 days. Hazard ratios (HRs) comparing randomized treatments were derived from univariate Cox regression models. Subgroups were analyzed with a Cox model including subgroup, treatment, and the subgroup-by-treatment interaction.

Results:

Of 18,624 patients hospitalized for ACS, 11,289 (61%) had at least one intracoronary stent. Ticagrelor reduced stent thrombosis compared with clopidogrel across all definitions: definite, 1.37% (n = 71) versus 1.93% (n = 105; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50-0.90; p = 0.0091); definite or probable, 2.21% (n = 118) versus 2.87% (n = 157; HR, 0.75; 95% CI, 0.59-0.95; p = 0.017); and definite, probable, and possible, 2.94% (n = 154) versus 3.77 (n = 201; HR, 0.77; 95% CI, 0.62-0.95). The reduction in definite stent thrombosis was consistent regardless of ACS type, presence of diabetes mellitus, stent type (drug-eluting or bare-metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel before randomization, and use of glycoprotein IIb/IIIa inhibitors at randomization. The reduction in stent thrombosis with ticagrelor was numerically greater for late (>30 days; HR, 0.48; 95% CI, 0.24-0.96) and subacute (4 hours–30 days; HR, 0.60; 95% CI, 0.39-0.93) compared with acute (<24 hours; HR, 0.94; 95% CI, 0.43-2.05) stent thrombosis or for patients compliant to therapy (i.e., taking blinded study treatment ≥80% of the time) compared with less compliant patients. Randomization to ticagrelor was a strong independent inverse predictor of definite stent thrombosis (HR, 0.65; 95% CI, 0.48-0.88).

Conclusions:

The authors concluded that ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with ACS.

Perspective:

This subgroup analysis of the PLATO trial reported that ticagrelor compared with clopidogrel reduced the incidence of stent thrombosis, regardless of the definition used. The benefit of ticagrelor in reducing definite stent thrombosis appeared to be independent of baseline variables such as type of ACS, diabetes mellitus, geographic region of enrollment, clopidogrel CYP2C19 genotype, prerandomization dose of aspirin and clopidogrel, and stent type (bare-metal or drug-eluting stent). Stent thrombosis had dire consequences, with a dramatic increase in all-cause mortality and bleeding rates, and clinicians may need to consider this advantage along with overall efficacy and safety while choosing optimal dual antiplatelet therapy for patients with ACS.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS

Keywords: Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Thrombosis, Stents, Percutaneous Coronary Intervention


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