Stent Thrombosis with Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes: An Analysis from the Prospective Randomized PLATO Trial

• Original Article

Stent Thrombosis with Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes: An Analysis from the Prospective Randomized PLATO Trial

1. Ph. Gabriel Steg1*;
2. Robert A. Harrington2;
3. Hakan Emanuelsson3;
4. Hugo A. Katus4;
5. Kenneth W. Mahaffey5;
6. Bernhard Meier6;
7. Robert F. Storey7;
8. Daniel M. Wojdyla5;
9. Basil S. Lewis8;
10. Gerald Maurer9;
11. Lars Wallentin10;
12. Stefan K. James10;
13. for the PLATO study group

+ Author Affiliations

1. ¹INSERM-Unité 698; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France
2. ²Stanford University, Stanford, CA
3. ³Astra Zeneca R&D, Mölndal, Sweden
4. ⁴Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany
5. ⁵Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
6. ⁶Bern University Hospital, Bern, Switzerland
7. ⁷University of Sheffield, Sheffield, UK
8. ⁸Lady Davis Carmel Medical Center, Haifa, Israel
9. ⁹Medical University of Vienna, Vienna, Austria
10. ¹⁰Uppsala University, Uppsala, Sweden

1. ↵* Hôpital Bichat, 46 Rue H. Huchard, 75018 Paris, France gabriel.steg@bch.aphp.fr

Abstract

Background—We aimed to describe the effects of ticagrelor vs. clopidogrel on stent thrombosis in the PLATelet inhibition and patient Outcomes (PLATO) trial.

Methods and Results—Of 18,624 patients hospitalized for ACS, 11,289 (61%) had at least one intracoronary stent. Ticagrelor reduced stent thrombosis vs. clopidogrel across all definitions: definite 1.37% (n=71) vs. 1.93% (n=105); (HR 0.67, 95% confidence interval [CI] (0.50 - 0.90), p= 0.0091) definite or probable 2.21% (n=118) vs. 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) vs. 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, diabetes, stent type (drug-eluting or bare metal), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel pre-randomization, and use of GpIIb/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 [24 h - 30 days: HR 0.60, 95% CI (0.39 - 0.93)] vs. acute stent thrombosis [< 24 h: HR 0.94 95% CI (0.43 - 2.05)], or for patients compliant to therapy (i.e. taking blinded study treatment ≥ 80% of the time) vs 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—Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in ACS patients, with consistent benefit across a broad range of patient, stent and treatment characteristics.

Clinical Trial Registration Information—http://www.clinicalTrials.gov. Identifier: NCT00391872.

Key Words:

• platelet
• stent thrombosis
• thrombosis

• Received March 13, 2013.
• Revision received July 7, 2013.
• Accepted July 12, 2013.