Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina

S. Yusuf, J. Pogue, S. Anand, G. Tognoni, K. Fox, R. Díaz, E. Paolasso, D. Hunt, J. Varigos, A. Avezum, L. Piegas, C. Joyner, P. Theroux, H. Rupprecht, T. Wittlinger, N. Karatzasy, M. Keltai, E. Sitkei, D. Halon, B. S. LewisM. G. Franzosi, M. Galli, A. Maggioni, F. Mauri, M. Ramos-Corrales, A. Budaj, L. Ceremuzynski, P. Commerford, M. Flather, J. Anderson, J. Hirsh, J. Cairns, M. Gent, R. Gorlin, J. Willerson, J. Wittes, G. Wyse, P. Auger, Y. K. Chan, H. Hernandez, M. Kyriakidis, J. F. Marquis, B. Mayosi, S. Mehta, M. Natarajan, A. Panju, E. Paolasso, C. Rihal, B. Sussex, W. Wasek, B. Cracknell, J. Lindeman, J. Mackay, H. Marsh, M. Anderson, M. Sloan, I. Stoica, J. Tucker, F. Cherian, C. Christmas, C. Cuvay, I. Holadyk-Gris, S. Kotlan, F. Mazur, M. Micks, K. Nair, L. Robinson, S. Seitz, S. Smith, L. Tomic, A. Gafni, A. Lamy, J. Pogue, C. Sigouin, J. Brown, L. Cronin, M. Johnston, J. Weitz

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Abstract

OBJECTIVES: We sought to evaluate whether oral anticoagulant (AC) therapy given for five months was superior to standard (control) therapy in patients with unstable angina receiving aspirin. BACKGROUND: The long-term risk of myocardial infarction (MI) or death remains high in patients with unstable angina, despite the use of aspirin. Therefore, additional treatments are necessary. METHODS: Of the 10,141 patients entering the main trial, 3,712 were randomized 12 to 48 h later to receive oral AC therapy (n = 1,848) or standard therapy (n = 1,864). RESULTS: One-hundred forty patients (7.6%) suffered from cardiovascular death, MI or stroke while receiving oral AC, compared with 155 patients (8.3%) on standard therapy (relative risk [RR] 0.90, 95% confidence interval [CI] 0.72 to 1.14; p = 0.40). The rates of the primary outcomes plus refractory angina were 16.7% (n = 308) versus 17.5% (n = 327) (RR 0.95, 95% CI 0.81 to 1.11; p = 0.53). Countries were divided into good or poor compliers (based on the use of oral AC above or below 70% at 35 days), without knowledge of results by country. In good-compiler countries, oral AC was discontinued in only 10.4% of patients at seven days and in 23.6% by five months, compared with 27.6% and 44.9%, respectively, in poor complier countries. There were significant reductions in the risks of both the primary (6.1% vs. 8.9%; RR 0.68, 95% CI 0.48 to 0.95; p = 0.02) and secondary outcomes (11.9% vs. 16.5%; RR 0.70, 95% CI 0.55 to 0.90; p = 0.005) with oral AC in the good-complier countries. There was little difference in the poor-complier countries (9.0% vs. 7.8% for the primary and 21.3% vs. 18.5% for the secondary outcomes, tests for interactions comparing the RRs for the primary and secondary outcomes were p < 0.02 and p = 0.002, respectively, between the two sets of countries). In the overall study, there was an excess of major bleeding (2.7% vs. 1.3%; p = 0.004), which was larger in the good-complier countries (RR 2.71) compared with the poor-complier countries (RR 1.58). There were also reductions in cardiac catheterization (RR 0.80; p = 0.004) and coronary revascularization procedures (RR 0.82; p = 0.06) in the good-complier countries, but not in the poor-complier countries (RR 0.98 and 1.06, respectively, p for interaction of 0.06 and 0.04, respectively). CONCLUSIONS: Overall, oral AC led to a small, nonsignificant reduction in the risk of the primary and secondary outcomes. Stratifying the countries or centers by their rates of compliance to oral AC suggested that good compliance to oral AC could potentially lead to clinically important reductions in major ischemic cardiovascular events.

Original languageEnglish (US)
Pages (from-to)475-484
Number of pages10
JournalJournal of the American College of Cardiology
Volume37
Issue number2
DOIs
StatePublished - Feb 22 2001

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Yusuf, S., Pogue, J., Anand, S., Tognoni, G., Fox, K., Díaz, R., Paolasso, E., Hunt, D., Varigos, J., Avezum, A., Piegas, L., Joyner, C., Theroux, P., Rupprecht, H., Wittlinger, T., Karatzasy, N., Keltai, M., Sitkei, E., Halon, D., ... Weitz, J. (2001). Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. Journal of the American College of Cardiology, 37(2), 475-484. https://doi.org/10.1016/S0735-1097(00)01118-9