Elsevier

American Heart Journal

Volume 154, Issue 6, December 2007, Pages 1085.e1-1085.e6
American Heart Journal

Clinical Investigations
Acute Ischemic Heart Disease
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

https://doi.org/10.1016/j.ahj.2007.08.029Get rights and content

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.

Section snippets

Eligibility and search strategy

We obtained results from all RTs on adjunctive LMWHs as compared to 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 and scientific session abstracts in Circulation, Journal of College of Cardiology, European Heart Journal, and American Journal of Cardiology from January 1990 to June 2007. Furthermore, oral presentations and/or expert slide presentations were

Results

We identified a total of 8 RTs (Table I),9, 10, 11, 12, 13, 14, 15, 16 including 13 940 patients randomized to LMWHs and 13 818 to UFH. Three studies used tenecteplase,9, 11, 12, 13, 14 2 alteplase,10, 13 1 streptokinase,14 1 urokinase,16 a mixture in the EXTRACT-TIMI 25.15 One study did not administer aspirin until the fourth day16; the remaining studies for which this information was available administered at least 150 mg initially.9, 12, 13, 14, 15, 16 The maintenance dose of aspirin was

Discussion

The results of our meta-analysis of 8 RTs, including 27 758 patients, show that LMWHs are associated with a significant reduction in reinfarction, trend in benefits in mortality, but higher risk of major bleeding complications.

Even though the benefits in mortality and reinfarction with UFH have not been proven, intravenous UFH remains a pivotal antithrombotic therapy among patients with STEMI, particularly in Western countries in which fibrin-specific thrombolytic agents are widely used,17, 18

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