Published online before print December 12, 2005, doi: 10.1161/CIRCULATIONAHA.105.573550
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(Circulation. 2005;112:3855-3867.)
© 2005 American Heart Association, Inc.
Coronary Heart Disease |
Unfractionated and Low-Molecular-Weight Heparin as Adjuncts to Thrombolysis in Aspirin-Treated Patients With ST-Elevation Acute Myocardial Infarction
A Meta-Analysis of the Randomized Trials
From the Thrombosis Service, Hamilton Health Sciences, General Division (J.W.E., A.G.T.), Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (J.W.E., S.R.M., A.G.G., S.Y.); Department of Radiology, Kings College Hospital, London, UK (D.J.Q.); Population Health Research Institute, Hamilton General Hospital, Hamilton, Ontario, Canada (S.R.M., S.Y.); and Department of Cardiology, Craigavon Area Hospital, Northern Ireland, UK (I.B.M.).
Correspondence to Daniel J. Quinlan, Department of Radiology, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK. E-mail dan.quinlan{at}consultoberon.com
Received July 4, 2005; revision received August 31, 2005; accepted September 27, 2005.
Background— There is uncertainty about the role of intravenous unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in patients with ST-elevation myocardial infarction (STEMI) treated with aspirin and thrombolysis.
Methods and Results— We performed a meta-analysis of the randomized trials to assess the effect of UFH and LMWH on reinfarction, death, stroke, and bleeding. Fourteen trials involving a total of 25 280 patients were included (1239 comparing intravenous UFH versus placebo or no heparin; 16 943 comparing LMWH versus placebo; and 7098 comparing LMWH versus intravenous UFH). Intravenous UFH during hospitalization did not reduce reinfarction (3.5% versus 3.3%; odds ratio [OR], 1.08; 95% CI, 0.58 to 1.99) or death (4.8% versus 4.6%; OR, 1.04; 95% CI, 0.62 to 1.78) and did not increase major bleeding (4.2% versus 3.4%; OR, 1.21; 95% CI, 0.67 to 2.18) but increased minor bleeding (19.6% versus 12.5%; OR, 1.72; 95% CI, 1.22 to 2.43). During hospitalization/at 7 days, LMWH compared with placebo reduced the risk of reinfarction by approximately one quarter (1.6% versus 2.2%; OR, 0.72; 95% CI, 0.58 to 0.90; number needed to treat [NNT]=167) and death by &10% (7.8% versus 8.7%; OR, 0.90; 95% CI, 0.80 to 0.99; NNT=111) but increased major bleeding (1.1% versus 0.4%; OR, 2.70; 95% CI, 1.83 to 3.99; number needed to harm [NNH]=143) and intracranial bleeding (0.3% versus 0.1%; OR, 2.18; 95% CI, 1.07 to 4.52; NNH=500). The reduction in death with LMWH remained evident at 30 days. LMWH compared with UFH during hospitalization/at 7 days reduced reinfarction by &45% (3.0% versus 5.2%; OR, 0.57; 95% CI, 0.45 to 0.73; NNT=45), did not reduce death (4.8% versus 5.3%; OR, 0.92; 95% CI, 0.74 to 1.13) or increase major bleeding (3.3% versus 2.5%; OR, 1.30; 95% CI, 0.98 to 1.72), but increased minor bleeding (22.8% vs 19.4%; OR, 1.26; 95% CI, 1.12 to 1.43). The reduction in reinfarction remained evident at 30 days.
Conclusions— In aspirin-treated patients with STEMI who are treated with thrombolysis, intravenous UFH has not been shown to prevent reinfarction or death. LMWH given for 4 to 8 days compared with placebo reduces reinfarction by approximately one quarter and death by &10% and when directly compared with UFH reduces reinfarction by almost one half. These data suggest that LMWH should be the preferred antithrombin in this setting.
Key Words: heparin • meta-analysis • myocardial infarction • thrombolysis
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