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The PCI-CLARITY Study

Marc S. Sabatine, MD, MPH; Christopher P. Cannon, MD; C. Michael Gibson, MD, MS; Jose L. López-Sendón, MD; Gilles Montalescot, MD, PhD; Pierre Theroux, MD; Basil S. Lewis, MD; Sabina A. Murphy, MPH; Carolyn H. McCabe, BS; Eugene Braunwald, MD; for the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)–Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators

JAMA. 2005;294:1224-1232.

Context  The benefit of clopidogrel pretreatment before percutaneous coronary intervention (PCI) remains debated and its use has not been universally adopted.

Objective  To determine if clopidogrel pretreatment before PCI in patients with recent ST-segment elevation myocardial infarction (STEMI) is superior to clopidogrel treatment initiated at the time of PCI in preventing major adverse cardiovascular events.

Design, Setting, and Participants  The PCI-Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) study was a prospectively planned analysis of the 1863 patients undergoing PCI after mandated angiography in CLARITY–Thrombolysis in Myocardial Infarction (TIMI) 28, a randomized, double-blind, placebo-controlled trial of clopidogrel in patients receiving fibrinolytics for STEMI. Patients were enrolled at 319 sites in 23 countries from February 2003 through October 2004.

Interventions  Patients received aspirin and were randomized to receive either clopidogrel (300 mg loading dose, then 75 mg once daily) or placebo initiated with fibrinolysis and given until coronary angiography, which was performed 2 to 8 days after initiation of the study drug. For patients undergoing coronary artery stenting, it was recommended that open-label clopidogrel (including a loading dose) be administered after the diagnostic angiogram.

Main Outcome Measures  The primary outcome was the incidence of the composite of cardiovascular death, recurrent MI, or stroke from PCI to 30 days after randomization. Secondary outcomes included MI or stroke before PCI and the aforementioned composite from randomization to 30 days.

Results  Pretreatment with clopidogrel significantly reduced the incidence of cardiovascular death, MI, or stroke following PCI (34 [3.6%] vs 58 [6.2%]; adjusted odds ratio [OR], 0.54 [95% CI, 0.35-0.85]; P = .008). Pretreatment with clopidogrel also reduced the incidence of MI or stroke prior to PCI (37 [4.0%] vs 58 [6.2%]; OR, 0.62 [95% CI, 0.40-0.95]; P = .03). Overall, pretreatment with clopidogrel resulted in a highly significant reduction in cardiovascular death, MI, or stroke from randomization through 30 days (70 [7.5%] vs 112 [12.0%]; adjusted OR, 0.59 [95% CI, 0.43-0.81]; P = .001; number needed to treat = 23). There was no significant excess in the rates of TIMI major or minor bleeding (18 [2.0%] vs 17 [1.9%]; P>.99).

Conclusions  Clopidogrel pretreatment significantly reduces the incidence of cardiovascular death or ischemic complications both before and after PCI and without a significant increase in major or minor bleeding. These data add further support to the early use of clopidogrel in STEMI and the strategy of routine clopidogrel pretreatment in patients undergoing PCI.

Author Affiliations: The Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (Drs Sabatine, Cannon, Gibson, and Braunwald, and Mss Murphy and McCabe); Cardiology Department, Hospital Universitario La Paz, Madrid, Spain (Dr López-Sendón); Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France (Dr Montalescot); Department of Medicine, Montreal Heart Institute, Montreal, Quebec (Dr Theroux); and Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center and Ruth and Bruce Rappaport School of Medicine, Haifa, Israel (Dr Lewis).

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