Adjunctive benefits from low-molecular-weight heparins as compared to unfractionated heparin among patients with ST-segment elevation myocardial infarction treated with thrombolysis. A meta-analysis of the randomized trials

Abstract

Background: Improvement in adjunctive antithrombotic therapy is a key point in pharmacologic reperfusion for ST-segment elevation myocardial infarction (STEMI). The aim of the current study was to perform an updated meta-analysis of all randomized trials comparing low-molecular-weight heparins (LMWHs) versus unfractionated heparin (UFH) in patients with STEMI treated with thrombolysis.

Methods: We obtained results from all randomized trials comparing LMWHs versus UFH among patients with STEMI treated with thrombolysis. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to June 2007. The following keywords were used: randomized trial, myocardial infarction, reperfusion, thrombolysis, duteplase, reteplase, tenecteplase, alteplase, UFH, LMWHs, dalteparin, nadroparin, enoxaparin, reviparin, parnaparin. Clinical end points assessed were mortality and reinfarction at 30-day follow-up, whereas major bleeding complications were assessed as safety end point. The relationship between mortality benefits from LMWHs and patient's risk profile was evaluated by using a weighted least-square regression in which results from each trial were weighted by the square root of the number of patients in each trial. No language restriction was applied.

Results: We identified a total of 8 randomized trials, including 13,940 patients randomized to LMWHs and 13,818 to UFH. Low-molecular-weight heparins were associated with a trend in reduction in mortality (6.6% vs 7.2%, odds ratio [OR] 0.92, 95% CI 0.84-1.01, P = .08, P heterogeneity [P het] = 0.7) and significant reduction in reinfarction (3.2% vs 4.8%, OR 0.65, 95% CI 0.58-0.64, P < .0001, P het = 0.39), but a higher risk of major bleeding complications (2.4% vs 1.8%, OR 1.37, 95% CI 1.16-1.61, P < .001, P het = 0.32).

Conclusions: Among patients with STEMI treated with thrombolysis, LMWHs, as compared to UFH, are associated with a trend in mortality benefits and a significant reduction in reinfarction (reMI) at 30-day follow-up, but with higher risk of major bleeding complications. In view of the additional practical advantages, such as reduced interindividual variability in therapeutic response and no need for frequent activated partial thromboplastin time (aPTT) monitoring and dose adjustment, LMWHs should be considered, instead of UFH, among patients with STEMI treated with thrombolysis.