Published Online
on November 15, 2005

A more recent version of this article appeared on December 20, 2005

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Submitted on October 14, 2005
Revised on October 25, 2005
Accepted on November 1, 2005

Angiographic and Clinical Outcomes in Patients Receiving Low-Molecular-Weight Heparin Versus Unfractionated Heparin in ST-Elevation Myocardial Infarction Treated With Fibrinolytics in the CLARITY-TIMI 28 Trial

Marc S. Sabatine MD, MPH^*, David A. Morrow MD, MPH, Gilles Montalescot MD, PhD, Mikael Dellborg MD, Jose L. Leiva-Pons MD, Matyas Keltai MD, Sabina A. Murphy MPH, Carolyn H. McCabe BS, C. Michael Gibson MD, MS, Christopher P. Cannon MD, Elliott M. Antman MD, Eugene Braunwald MD, for the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators

From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (M.S.S., D.A.M., S.A.M., C.H.M., C.M.G., C.P.C., E.M.A., E.B.); Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France (G.M.); Department of Medicine, Sahlgrenska University Hospital, Goteborg, Sweden (M.D.); Interventional Cardiology, Department Hospital Central San Luis Potosi, Mexico (J.L.L.-P.); and Department of Cardiology, Semmelweis University, Hungarian Institute of Cardiology, Budapest, Hungary (M.K.).

^* To whom correspondence should be addressed. E-mail: msabatine{at}partners.org.

Background--Low-molecular-weight heparin (LMWH) offers pharmacological and practical advantages over unfractionated heparin (UFH). Whether these advantages translate into greater infarct-related artery patency and fewer adverse clinical events in patients with ST-elevation myocardial infarction (STEMI) receiving fibrinolytic therapy remains under study.

Methods and Results--We compared angiographic and clinical outcomes in patients treated with LMWH (n=1429) versus UFH (n=1431) in CLARITY-TIMI 28, a randomized trial of clopidogrel versus placebo in STEMI patients aged 18 to 75 years undergoing fibrinolysis. After comprehensive adjustment for baseline characteristics, therapeutic interventions, and a propensity score, treatment with LMWH was associated with a significantly lower rate of a closed infarct-related artery or death or myocardial infarction before angiography (13.5% versus 22.5%, adjusted OR 0.76, P=0.027). Treatment with LMWH was also associated with a significantly lower rate of cardiovascular death or recurrent myocardial infarction through 30 days (6.9% versus 11.5%, adjusted OR 0.68, P=0.030). The lower event rates were observed in patients allocated to clopidogrel and in those who underwent percutaneous coronary intervention. Rates of TIMI major bleeding through 30 days (1.6% versus 2.2%, P=0.27) and intracranial hemorrhage (0.6% versus 0.8%, P=0.37) were similar in the LMWH and UFH groups. Patients who received both clopidogrel and LMWH, in addition to a standard fibrinolytic and aspirin, had a particularly high rate of infarct-related artery patency (90.9%) and particularly low rates of cardiovascular death (3.2%), recurrent myocardial infarction (3.0%), and major bleeding (1.8%).

Conclusions--In patients with STEMI receiving fibrinolytic therapy, use of LMWH with other standard therapies, including clopidogrel and aspirin, is associated with improved angiographic outcomes and lower rates of major adverse cardiovascular events.

Key words: myocardial infarction • heparin • fibrinolysis • angiography

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