Blog
About

18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Inhibition of the Platelet Glycoprotein IIb/IIIa Receptor with Tirofiban in Unstable Angina and Non–Q-Wave Myocardial Infarction

      New England Journal of Medicine

      Massachusetts Medical Society

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Antithrombotic therapy improves the prognosis of patients with acute coronary syndromes, yet the syndromes remain a therapeutic challenge. We evaluated tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, in the treatment of unstable angina and non-Q-wave myocardial infarction. A total of 1915 patients were randomly assigned in a double-blind manner to receive tirofiban, heparin, or tirofiban plus heparin. Patients received aspirin if its use was not contraindicated. The study drugs were infused for a mean (+/-SD) of 71.3+/-20 hours, during which time coronary angiography and angioplasty were performed when indicated after 48 hours. The composite primary end point consisted of death, myocardial infarction, or refractory ischemia within seven days after randomization. The study was stopped prematurely for the group receiving tirofiban alone because of excess mortality at seven days (4.6 percent, as compared with 1.1 percent for the patients treated with heparin alone. The frequency of the composite primary end point at seven days was lower among the patients who received tirofiban plus heparin than among those who received heparin alone (12.9 percent vs. 17.9 percent; risk ratio, 0.68; 95 percent confidence interval, 0.53 to 0.88; P=0.004). The rates of the composite end point in the tirofiban-plus-heparin group were also lower than those in the heparin-only group at 30 days (18.5 percent vs. 22.3 percent, P=0.03) and at 6 months (27.7 percent vs. 32.1 percent, P=0.02). At seven days, the frequency of death or myocardial infarction was 4.9 percent in the tirofiban-plus-heparin group, as compared with 8.3 percent in the heparin-only group (P=0.006). The comparable figures at 30 days were 8.7 percent and 11.9 percent (P=0.03), respectively, and those at 6 months were 12.3 percent and 15.3 percent (P=0.06). The benefit was consistent in the various subgroups of patients and in those treated medically as well as those treated with angioplasty. Major bleeding occurred in 3.0 percent of the patients receiving heparin alone and 4.0 percent of the patients receiving combination therapy (P=0.34). When administered with heparin and aspirin, the platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was associated with a lower incidence of ischemic events in patients with acute coronary syndromes than in patients who received only heparin and aspirin.

          Related collections

          Most cited references 24

          • Record: found
          • Abstract: not found
          • Article: not found

          The pathogenesis of coronary artery disease and the acute coronary syndromes (1).

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge.

            Intravenous administration of 80 mg of recombinant tissue plasminogen activator (rt-PA, 40, 20, and 20 mg in successive hours) and streptokinase (SK, 1.5 million units over 1 hr) was compared in a double-blind, randomized trial in 290 patients with evolving acute myocardial infarction. These patients entered the trial within 7 hr of the onset of symptoms and underwent baseline coronary arteriography before thrombolytic therapy was instituted. Ninety minutes after the start of thrombolytic therapy, occluded infarct-related arteries had opened in 62% of 113 patients in the rt-PA and 31% of 119 patients in the SK group (p less than .001). Twice as many occluded infarct-related arteries opened after rt-PA compared with SK at the time of each of seven angiograms obtained during the first 90 min after commencing thrombolytic therapy. Regardless of the time from onset of symptoms to treatment, more arteries were opened after rt-PA than SK. The reduction in circulating fibrinogen and plasminogen and the increase in circulating fibrin split products at 3 and 24 hr were significantly less in patients treated with rt-PA than in those treated with SK (p less than .001). The occurrence of bleeding events, administration of blood transfusions, and reocclusion of the infarct-related artery was comparable in the two groups. Thus, in patients with acute myocardial infarction, rt-PA elicited reperfusion in twice as many occluded infarct-related arteries as compared with SK at each of seven serial observations during the first 90 min after onset of treatment.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation.

               RM Califf (1994)
              Platelets are believed to play a part in the ischemic complications of coronary angioplasty, such as abrupt closure of the coronary vessel during or soon after the procedure. Accordingly, we evaluated the effect of a chimeric monoclonal-antibody Fab fragment (c7E3 Fab) directed against the platelet glycoprotein IIb/IIIa receptor, in patients undergoing angioplasty who were at high risk for ischemic complications. This receptor is the final common pathway for platelet aggregation. In a prospective, randomized, double-blind trial, 2099 patients treated at 56 centers received a bolus and an infusion of placebo, a bolus of c7E3 Fab and an infusion of placebo, or a bolus and an infusion of c7E3 Fab. They were scheduled to undergo coronary angioplasty or atherectomy in high-risk clinical situations involving severe unstable angina, evolving acute myocardial infarction, or high-risk coronary morphologic characteristics. The primary study end point consisted of any of the following: death, nonfatal myocardial infarction, unplanned surgical revascularization, unplanned repeat percutaneous procedure, unplanned implantation of a coronary stent, or insertion of an intraaortic balloon pump for refractory ischemia. The numbers of end-point events were tabulated for 30 days after randomization. As compared with placebo, the c7E3 Fab bolus and infusion resulted in a 35 percent reduction in the rate of the primary end point (12.8 vs. 8.3 percent, P = 0.008), whereas a 10 percent reduction was observed with the c7E3 Fab bolus alone (12.8 vs. 11.5 percent, P = 0.43). The reduction in the number of events with the c7E3 Fab bolus and infusion was consistent across the end points of unplanned revascularization procedures and nonfatal myocardial infarction. Bleeding episodes and transfusions were more frequent in the group given the c7E3 Fab bolus and infusion than in the other two groups. Ischemic complications of coronary angioplasty and atherectomy were reduced with a monoclonal antibody directed against the platelet IIb/IIIa glycoprotein receptor, although the risk of bleeding was increased.
                Bookmark

                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                May 21 1998
                May 21 1998
                : 338
                : 21
                : 1488-1497
                Article
                10.1056/NEJM199805213382102
                9599103
                © 1998

                Comments

                Comment on this article