Randomized Comparison of Enoxaparin, a Low-Molecular-Weight Heparin, With Unfractionated Heparin Adjunctive to Recombinant Tissue Plasminogen Activator Thrombolysis and Aspirin

Abstract

Background-Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecularweight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. Methods and Results-Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. Conclusions-Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days. (Circulation. 2001;104:648-652.)

Low-Molecular-Weight Heparins in Conjunction with Thrombolysis for ST-Elevation Acute Myocardial Infarction

“…Of all the studies identified, 12 fulfilled criteria for analysis, including 26,831 patients overall [21,22,23,24,25,26,27,28,29,30,31,32]. LMWH evaluated in these studies were dalteparin, enoxaparin and reviparin.…”

“…Out of the eight trials (9,945 patients) evaluating enoxaparin [24,25,26,27,28,29,30,31], thrombolysis was carried out with streptokinase in three [24, 29, 31], with tenecteplase in another three [26, 27, 30], with alteplase in one [25], and with tenecteplase or streptokinase or anistreplase in another one [28]. In a single study, no anti-platelet therapy with aspirin was given until day 4 [28].…”

“…In the HART-II study [25], the TIMI 2-3 (80 vs. 75%) and TIMI 3 (53 vs. 48%) grades flow in the IRA did not significantly differ at 90ʼ in the two groups treated with enoxaparin and UFH. Also, the reocclusion rate at 5–7 days was comparable, although a clear trend favoring enoxaparin was evident (3 vs. 9%).…”

“…Relative to the angiographic efficacy end-points, no significant differences were observed with LMWH compared to UFH on the acute (60–90ʼ to 24 h) patency rate of the IRA [22, 25, 27]. On the other hand, late patency (4–10 days) and/or reocclusion rates of the IRA were, in general, favorably influenced by LMWH treatment, although statistical significance was seldom reached [23, 25, 29].…”

“…On the other hand, late patency (4–10 days) and/or reocclusion rates of the IRA were, in general, favorably influenced by LMWH treatment, although statistical significance was seldom reached [23, 25, 29]. Possible explanations for that include both the small size and the design of the studies, where LMWH were compared sometimes to placebo [22, 29] and some other times to UFH [23, 25, 27]. …”