A substudy of the GUSTO trial concluded that tissueplasminogen activator's more rapid restoration of coronary-artery patency seems to account for t-PA's higher survival ratecompared with streptokinase.

The substudy of the GUSTO (Global Utilization of Streptokinaseand t-PA for Occluded Coronary Arteries) trial is published inlast week's issue of the New England Journal of Medicine(NEJM). In this trial, 2,431 patients who participated in GUSTOwere randomly assigned to one of four treatment groups forreperfusion. They also were randomly assigned to cardiacangiography at one of four times after the initiation ofthrombolytic therapy (90 minutes, 180 minutes, 24 hours orfive to seven days).

The investigators reported that "the rate of patency of theinfarct-related artery at 90 minutes was highest in the groupgiven accelerated dose t-PA and heparin (81 percent), ascompared with the group given streptokinase andsubcutaneous heparin (54 percent, p less than 0.001), thegroup given streptokinase and intravenous heparin (60percent, p less than 0.001), and the group given combinationtherapy (73 percent, p equals 0.032)."

In addition, they said that "flow through the infarct-relatedartery at 90 minutes was normal in 54 percent of the groupgiven t-PA and heparin but in less than 40 percent of the threeother groups (p less than 0.001)." The patency rates were thesame in the four treatment groups by 180 minutes.

The GUSTO trial of 41,000 heart attack patients found thatGenentech Inc.'s t-PA statistically saved one more heart attackpatient per 100 than streptokinase. Treatment with t-PA costsabout $2,000, while treatment with streptokinase is about$200. The results were reported in the Sept. 2 issue of NEJM.

Two previous trials, the 12,000-patient GISSI-2 (GruppoItaliano per lo Studio della Streptochinasi nell'InfartoMiocardico) and the 46,000-patient ISIS-3 (the ThirdInternational Study of Infarct Survival), found no difference inmortality between patients treated with t-PA andstreptokinase. The studies also found that streptokinase-treated patients had significantly fewer strokes than patientstreated with either t-PA or Burroughs Wellcome Co.'s APSAC.

In a NEJM editorial, Eugene Braunwald of Brigham andWomen's Hospital said the GUSTO trial differed from the twoearlier trials in that t-PA was administered in an acceleratedway to enhance the early establishment of patency andintravenous heparin with aspirin "was begun with thethrombolytic agent and was continued to reduce the risk ofreocclusion."

He said the GUSTO angiographic substudy "resoundinglyconfirms" the theory that early opening of the infarct-relatedcoronary artery improves survival.

-- Brenda Sandburg News Editor

(c) 1997 American Health Consultants. All rights reserved.