Stent thrombosis with ticagrelor versus clopidogrel in patients with acute coronary syndromes: an analysis from the prospective, randomized PLATO trial

Circulation. 2013 Sep 3;128(10):1055-65. doi: 10.1161/CIRCULATIONAHA.113.002589. Epub 2013 Jul 30.

Abstract

Background: We aimed to describe the effects of ticagrelor versus clopidogrel on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial.

Methods and results: Of 18 624 patients hospitalized for acute coronary syndromes, 11 289 (61%) had at least 1 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 acute coronary syndrome 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 (ie, 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).

Conclusion: Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with acute coronary syndromes, with consistent benefit across a broad range of patient, stent, and treatment characteristics.

Trial registration: ClinicalTrials.gov NCT00391872.

Keywords: blood platelets; stents; thrombosis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / epidemiology
  • Acute Coronary Syndrome / surgery
  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Aged
  • Clopidogrel
  • Coronary Thrombosis / drug therapy*
  • Coronary Thrombosis / epidemiology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Heart Diseases / drug therapy
  • Heart Diseases / epidemiology
  • Humans
  • Internationality*
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Risk Factors
  • Stents / adverse effects*
  • Ticagrelor
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Ticagrelor
  • Adenosine
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT00391872