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Previous Volume 338:1488-1497 May 21, 1998 Number 21 Next

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ABSTRACT

Background 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.

Methods 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.

Results 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).

Conclusions 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.

Source Information

Address reprint requests to Dr. Pierre Théroux at the Montreal Heart Institute, 5000 Belanger St. E., Montreal, QC H1T 1C8, Canada.

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Tirofiban in Unstable Coronary Disease
Liron M., Théroux P., White H. D., The PRISM Study Investigators , Chesebro J. H., Badimon J. J.
Extract | Full Text  
N Engl J Med 1998; 339:1163-1165, Oct 15, 1998. Correspondence

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• Ottervanger, J.P., Armstrong, P., Barnathan, E.S., Boersma, E., Cooper, J.S., Ohman, E.M., James, S., Wallentin, L., Simoons, M.L., For the GUSTO IV-ACS Investigators, (2004). Association of revascularisation with low mortality in non-ST elevation acute coronary syndrome, a report from GUSTO IV-ACS. Eur Heart J 25: 1494-1501 [Abstract] [Full Text]  
• Shore-Lesserson, L., Tanaka, K. A., Levy, J. H., Pothula, S., Sanchala, V. T., Nagappala, B., Inchiosa, M. A. Jr. (2004). Antiplatelet Agents and Bleeding After Cardiac Surgery * Response. Anesth. Analg. 99: 947-948 [Full Text]  
• Patrono, C., Coller, B., FitzGerald, G. A., Hirsh, J., Roth, G. (2004). Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 234S-264S [Abstract] [Full Text]  
• Harrington, R. A., Becker, R. C., Ezekowitz, M., Meade, T. W., O'Connor, C. M., Vorchheimer, D. A., Guyatt, G. H. (2004). Antithrombotic Therapy for Coronary Artery Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 513S-548S [Abstract] [Full Text]  
• Popma, J. J., Berger, P., Ohman, E. M., Harrington, R. A., Grines, C., Weitz, J. I. (2004). Antithrombotic Therapy During Percutaneous Coronary Intervention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 576S-599S [Abstract] [Full Text]  
• Lincoff, A. M., Kleiman, N. S., Kereiakes, D. J., Feit, F., Bittl, J. A., Jackman, J. D., Sarembock, I. J., Cohen, D. J., Spriggs, D., Ebrahimi, R., Keren, G., Carr, J., Cohen, E. A., Betriu, A., Desmet, W., Rutsch, W., Wilcox, R. G., de Feyter, P. J., Vahanian, A., Topol, E. J., for the REPLACE-2 Investigators, (2004). Long-term Efficacy of Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade vs Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Revascularization: REPLACE-2 Randomized Trial. JAMA 292: 696-703 [Abstract] [Full Text]  
• Patel, J V, Bardgett, H (2004). Acute limb ischaemia. Imaging 16: 253-263 [Abstract] [Full Text]  
• Tanaka, K. A., Katori, N., Szlam, F., Sato, N., Kelly, A. B., Levy, J. H. (2004). Effects of tirofiban on haemostatic activation in vitro. Br J Anaesth 93: 263-269 [Abstract] [Full Text]  
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• SYNERGY Trial Investigators, (2004). Enoxaparin vs Unfractionated Heparin in High-Risk Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Managed With an Intended Early Invasive Strategy: Primary Results of the SYNERGY Randomized Trial. JAMA 292: 45-54 [Abstract] [Full Text]  
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• Day, J R S, Malik, I S, Weerasinghe, A, Poullis, M, Nadra, I, Haskard, D O, Taylor, K M, Landis, R C (2004). Distinct yet complementary mechanisms of heparin and glycoprotein IIb/IIIa inhibitors on platelet activation and aggregation: implications for restenosis during percutaneous coronary intervention. Heart 90: 794-799 [Abstract] [Full Text]  
• Simoons, M. L., Bobbink, I. W. G., Boland, J., Gardien, M., Klootwijk, P., Lensing, A. W. A., Ruzyllo, W., Umans, V. A. W. M., Vahanian, A., Van De Werf, F., Zeymer, U., PENTUA Investigators, (2004). A dose-finding study of fondaparinux in patients with non-ST-segment elevation acute coronary syndromes: The Pentasaccharide in Unstable Angina (PENTUA) study. J Am Coll Cardiol 43: 2183-2190 [Abstract] [Full Text]  
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• Brown, D. L., Desai, K. K., Vakili, B. A., Nouneh, C., Lee, H.-M., Golub, L. M. (2004). Clinical and Biochemical Results of the Metalloproteinase Inhibition with Subantimicrobial Doses of Doxycycline to Prevent Acute Coronary Syndromes (MIDAS) Pilot Trial. Arterioscler. Thromb. Vasc. Bio. 24: 733-738 [Abstract] [Full Text]  
• Lev, E. I., Hasdai, D., Scapa, E., Tobar, A., Assali, A., Lahav, J., Battler, A., Badimon, J. J., Kornowski, R. (2004). Administration of eptifibatide to acute coronary syndrome patients receiving enoxaparin or unfractionated heparin: Effect on platelet function and thrombus formation. J Am Coll Cardiol 43: 966-971 [Abstract] [Full Text]