Enoxaparin in acute coronary syndromes: Evidence for superiority over placebo or untreated control

Background Heparins, both standard unfractionated heparin (SUFH) and low-molecular weight heparin, play a prominent role in the treatment of acute coronary syndromes. Enoxaparin has been shown in 2 trials to be superior to heparin but has not been compared with placebo or untreated control. Methods A putative enoxaparin versus placebo/control odds ratio (OR) was computed with a recently described statistical technique with the logarithm of the ORs of the pooled results of both the enoxaparin-SUFH trials and SUFH-placebo or controlled trials. Results The combined heparin versus control results show a 33% reduction in the risk of death or acute myocardial infarction (AMI), with an OR of 0.67 (95% confidence interval [CI], 0.45 to 0.99). At up to 12 weeks (data from only 4 trials), the combined results show a 21% reduction (OR, 0.79; 95% CI, 0.54 to 1. 15; P = .23). The 2 enoxaparin trials show a nonsignificant 20% reduction in the risk of death or AMI during treatment (OR, 0.80; 95% CI, 0.68 to 1.16; P = .24) and a significant reduction at 43 days (OR, 0.82; 95% CI, 0.69 to 0.97; P = .022). With these pooled data, the putative OR for enoxaparin versus placebo/untreated control during treatment is 0.53 (95% CI, 0.31 to 0.92; P = .023). The data are consistent with a 47% reduction in the risk of death or AMI. The difference persists on longer term follow-up period (OR, 0.65; 95% CI, 0.43 to 0.98; P = .04). The risk of bleeding is nonsignificantly increased (OR, 2.32; 95% CI, 0.8 to 7.85; P = .51). Conclusion On the basis of this methodology, enoxaparin would appear to be more effective than placebo when added to aspirin in acute coronary syndromes. Moreover, the effect of enoxaparin is similar to the results of a metaanalysis of trials of other low-molecular weight heparins versus placebo/control.