A randomized controlled trial of intravenous tissue plasminogen activator and early intravenous heparin in acute myocardial infarction.

Abstract

To evaluate the coronary thrombolytic efficacy of tissue plasminogen activator (t-PA) and early intravenous heparin, 134 patients with acute myocardial infarction were randomly assigned to combination therapy or t-PA only. At a median of 2.78 hours from symptom onset, 64 patients received both t-PA (1.5 mg/kg/4 hr) and a bolus of 10,000 units heparin, whereas 70 patients received t-PA alone at the same dose. All patients underwent coronary angiography 90 minutes after initiation of therapy to determine infarct vessel patency status, after which time the control group patients were eligible to receive heparin. Baseline demographic and angiographic characteristics were similar for the groups. Infarct vessel patency was 50 of 63 (79%) for combination t-PA and heparin and 54 of 68 (79%o) for t-PA alone. Bleeding complications, as reflected by need for transfusion, were similar in the two groups: 13% in the patients treated with t-PA and heparin compared with 18% in patients treated with t-PA only (p=0.53). The only intracranial hemorrhage in the trial occurred in a patient initially treated without heparin. Fibrinogen at 50 minutes after therapy was 32% decreased from baseline for the t-PA and heparin-treated patients compared with a 39% decrease in the control group. Predischarge left ventricular ejection fraction was similar for the two groups: 49.0±10.1% versus 50.2±11.9% for combined versus t-PA only therapy, respectively. We conclude that early intravenous heparin does not facilitate the fibrinolytic effect of t-PA at the doses tested. If given, heparin therapy can be deferred for at least 60-90 minutes after t-PA has been initiated. (Circulation 1989;79:281-286

Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors.

“…Although heparin has proven to be an extremely effective antithrombotic agent, both experimental and clinical studies indicate that it is limited in its ability to inhibit the propagation of venous thrombi (14)(15)(16)(17)(18) or to prevent coronary rethrombosis after thrombolytic therapy (19,20). The studies presented here provide a plausible explanation for these limitations.…”

“…Heparin is an effective antithrombotic agent that acts primarily by catalyzing the inactivation of thrombin and activated Factor X by antithrombin III (8)(9)(10)(11) (19) or in man (20).…”

Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model.

“…To overcome this problem, several adjunctive therapies have been used with thrombolytic agents. Clinically, the use of aspirin, dipyridamole, calcium channel blockers, heparin, or nitrates have had little impact on the 20-30% acute rethrombosis rate with either streptokinase or rt-PA. [24][25][26] The model described in this study uses electrical induction of vessel wall injury as a means of promoting intracoronary artery thrombosis in the presence of a stenosis. The experimental models appears to mimic the clinical situation with respect to a spontaneously developing thrombus in response to endothelial injury.…”

Unfractionated and Low-Molecular-Weight Heparin as Adjuncts to Thrombolysis in Aspirin-Treated Patients With ST-Elevation Acute Myocardial Infarction

“…After review of abstracts, an additional 16 studies were excluded. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] After review of the full article, an additional 8 studies were excluded because they were not properly randomized (nϭ3) [33][34][35] ; because at least 1 randomized treatment group did not receive aspirin (nϭ3) 36 -38 ; or because they were preliminary reports or the results of a substudy with the main results having been reported elsewhere (nϭ2). 39,40 Clinical outcome data could not be obtained for 1 additional study, 41 leaving 14 randomized trials, involving a combined total of 25 280 patients, for inclusion in the meta-analysis (Tables 1 to 3).…”