Efegatran sulfate as an adjunct to streptokinase versus heparin as an adjunct to tissue plasminogen activator in patients with acute myocardial infarction. ESCALAT Investigators.

BACKGROUND: Previous clinical studies have shown that direct antithrombins can accelerate clot lysis after treatment with streptokinase in acute myocardial infarction (MI). Efegatran is a new direct antithrombin, which in experimental animals has been shown to enhance thrombolysis, reduce rate of reocclusion, and limit infarct size. This study was designed to compare the efficacy of efegatran plus streptokinase versus heparin plus accelerated tissue plasminogen activator (TPA) in coronary reperfusion in acute MI. METHODS AND RESULTS: In this randomized, dose-finding study (n = 245), we initially explored 4 doses of efegatran sulfate in combination with streptokinase (1.5 million U) given intravenously within 12 hours of symptom onset. The optimal dosage group of 0.5 mg/kg per hour was expanded and compared with heparin plus accelerated TPA. The primary end point was complete patency (Thrombolysis In Myocardial Infarction [TIMI] grade 3) at 90 minutes after thrombolytic therapy, assessed in a core angiographic laboratory. Infarct-related vessel patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) were 73% and 40% in the efegatran/streptokinase group versus 79% and 53% in the heparin/TPA group (P = not significant). In-hospital mortality rate was 5% for the efegatran/streptokinase group versus 0% for the heparin/TPA group (P = not significant). Major bleeding occurred in 23% of patients in the efegatran/streptokinase group versus 11% in the heparin/TPA group (P = not significant). No intracranial hemorrhage occurred. CONCLUSIONS: The combination of efegatran plus streptokinase is not superior to the current therapy of heparin and accelerated TPA in achieving early patency. In addition, there is no indication that this experimental treatment can achieve better clinical outcome.

Asymptomatic myocardial ischemia during percutaneous transluminal coronary angioplasty and importance of prior Q-wave infarction and diabetes mellitus.

Eighty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) of 100 stenoses were studied for the presence of factors deemed significant in the etiology of silent myocardial ischemia. Thirty-two patients were asymptomatic during balloon dilations of 36 arteries, and 56 patients had angina during PTCA of 64 arteries. There were no differences in age, sex, prior anginal history, antianginal regimen, extent of coronary artery disease and number or duration of inflations between the 2 study groups. Previous infarction (33 vs 12%, p less than 0.02), Q waves in the target area (31 vs 7%, p less than 0.005) and diabetes mellitus (36 vs 17%, p less than 0.05) were present more often in the asymptomatic group. Sixty-four% of all asymptomatic patients had either diabetes or previous infarction in the target territory. Collateral circulation was more frequent in asymptomatic patients, probably reflecting the ability of collateral arteries to ameliorate ischemia. During 2-vessel PTCA, patients without angina during dilation of only 1 of the 2 treated arteries (discordant responders) had previous infarction in that artery's territory (5 of 5, 100%), whereas patients without previous infarction were either symptomatic or asymptomatic (concordant responders) during PTCA of both arteries. This study shows that asymptomatic ischemia occurs frequently during PTCA in patients with symptomatic coronary disease. Prior Q-wave infarction and diabetes mellitus are important, independent factors associated with painless ischemia. It is suggested that infarction produces a localized dysfunction of afferent cardiac pain fibers, whereas diabetes can cause a global cardiac sensory neuropathy.

Distal embolization during mechanical thrombolysis: rotational thrombectomy vs. balloon angioplasty.

To determine the incidence and extent of distal embolization during percutaneous transluminal balloon angioplasty (PTA) and rotational thrombectomy (PRT), we collected, filtered, and weighed the distal effluent of acute thrombotically occluded canine arteries following mechanical thrombolysis. PRT (n = 11) and PTA (n = 10) were equally effective in recanalizing occluded vessels (91% vs. 90%) and reduced percent diameter stenosis to a similar degree (97 +/- 6% to 8 +/- 11% and 100 +/- 0% to 17 +/- 23%, respectively). Distal embolization following mechanical intervention was observed in 10 of 10 and 8 of 9 arteries recanalized with PRT and PTA, respectively. The mean weights of collected emboli were similar between the two groups (18 +/- 24 mg vs. 37 +/- 79 mg, PRT vs. PTA, P = NS), although the range of size and weight of thromboemboli was larger in the PTA group (0-206 mg vs. 2-51 mg, PRT). Angiographically defined residual thrombus was significantly less frequent in arteries recanalized with PRT as compared with PTA (10% vs. 55%, P = 0.03). In summary, PRT and PTA are equally effective in recanalizing acutely occluded canine arteries and result in similar reductions in percent diameter stenosis. Each intervention results in distal embolization of thrombi. PRT is associated with a reduced incidence of angiographically evident residual thrombus at the site of arterial injury and may avoid embolization of large fragments occasionally produced by PTA. Thus PRT may serve as a useful alternative to coronary angioplasty during acute myocardial infarction.

Inhibition of prostaglandin biosynthesis by eicosapentaenoic acid.

Eicosapentaenoic acid [20 : 5 (n-3)] is not oxidized by the purified cyclooxygenase from sheep vesicular glands in the conditions of low peroxide tone in which arachidonate [20 : 4 (n-6)] is rapidly oxygenated. When the level of peroxide in incubation mixtures is allowed to rise, there is a dramatic change in reactivity of the cyclooxygenase to react with 20 : 5 (n-3) at one-halt the rate and one-third the extent observed with 20 : 4 (n-6). Overall, the low peroxide levels expected in vivo would most probably cause the (n-3) type of fatty acid to be a general inhibitor of prostaglandin formation, through both reversible and irreversible actions at the enzyme site.