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

Research output: Contribution to journalArticle

99 Citations (Scopus)

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 - 2001
Externally publishedYes

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Unstable Angina
Aspirin
Anticoagulants
Confidence Intervals
Risk Reduction Behavior
Therapeutics
Myocardial Infarction
Cardiac Catheterization
Stroke
Hemorrhage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. / 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.; Lewis, B. S.; Franzosi, M. G.; Galli, M.; Maggioni, A.; Mauri, F.; Ramos-Corrales, M.; Budaj, A.; Ceremuzynski, L.; Commerford, P.; Flather, M.; Anderson, J.; Hirsh, J.; Cairns, J.; Gent, M.; Gorlin, R.; Willerson, J.; Wittes, J.; Wyse, G.; Auger, P.; Chan, Y. K.; Hernandez, H.; Kyriakidis, M.; Marquis, J. F.; Mayosi, B.; Mehta, S.; Natarajan, M.; Panju, A.; Paolasso, E.; Rihal, C.; Sussex, B.; Wasek, W.; Cracknell, B.; Lindeman, J.; Mackay, J.; Marsh, H.; Anderson, M.; Sloan, M.; Stoica, I.; Tucker, J.; Cherian, F.; Christmas, C.; Cuvay, C.; Holadyk-Gris, I.; Kotlan, S.; Mazur, F.; Micks, M.; Nair, K.; Robinson, L.; Seitz, S.; Smith, S.; Tomic, L.; Gafni, A.; Lamy, A.; Pogue, J.; Sigouin, C.; Brown, J.; Cronin, L.; Johnston, M.; Weitz, J.

In: Journal of the American College of Cardiology, Vol. 37, No. 2, 2001, p. 475-484.

Research output: Contribution to journalArticle

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, Lewis, BS, Franzosi, MG, Galli, M, Maggioni, A, Mauri, F, Ramos-Corrales, M, Budaj, A, Ceremuzynski, L, Commerford, P, Flather, M, Anderson, J, Hirsh, J, Cairns, J, Gent, M, Gorlin, R, Willerson, J, Wittes, J, Wyse, G, Auger, P, Chan, YK, Hernandez, H, Kyriakidis, M, Marquis, JF, Mayosi, B, Mehta, S, Natarajan, M, Panju, A, Paolasso, E, Rihal, C, Sussex, B, Wasek, W, Cracknell, B, Lindeman, J, Mackay, J, Marsh, H, Anderson, M, Sloan, M, Stoica, I, Tucker, J, Cherian, F, Christmas, C, Cuvay, C, Holadyk-Gris, I, Kotlan, S, Mazur, F, Micks, M, Nair, K, Robinson, L, Seitz, S, Smith, S, Tomic, L, Gafni, A, Lamy, A, Pogue, J, Sigouin, C, Brown, J, Cronin, L, Johnston, M & 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, vol. 37, no. 2, pp. 475-484. https://doi.org/10.1016/S0735-1097(00)01118-9
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. ; Lewis, B. S. ; Franzosi, M. G. ; Galli, M. ; Maggioni, A. ; Mauri, F. ; Ramos-Corrales, M. ; Budaj, A. ; Ceremuzynski, L. ; Commerford, P. ; Flather, M. ; Anderson, J. ; Hirsh, J. ; Cairns, J. ; Gent, M. ; Gorlin, R. ; Willerson, J. ; Wittes, J. ; Wyse, G. ; Auger, P. ; Chan, Y. K. ; Hernandez, H. ; Kyriakidis, M. ; Marquis, J. F. ; Mayosi, B. ; Mehta, S. ; Natarajan, M. ; Panju, A. ; Paolasso, E. ; Rihal, C. ; Sussex, B. ; Wasek, W. ; Cracknell, B. ; Lindeman, J. ; Mackay, J. ; Marsh, H. ; Anderson, M. ; Sloan, M. ; Stoica, I. ; Tucker, J. ; Cherian, F. ; Christmas, C. ; Cuvay, C. ; Holadyk-Gris, I. ; Kotlan, S. ; Mazur, F. ; Micks, M. ; Nair, K. ; Robinson, L. ; Seitz, S. ; Smith, S. ; Tomic, L. ; Gafni, A. ; Lamy, A. ; Pogue, J. ; Sigouin, C. ; Brown, J. ; Cronin, L. ; Johnston, M. ; Weitz, J. / Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. In: Journal of the American College of Cardiology. 2001 ; Vol. 37, No. 2. pp. 475-484.
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title = "Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina",
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.",
author = "S. Yusuf and J. Pogue and S. Anand and G. Tognoni and K. Fox and R. D{\'i}az and E. Paolasso and D. Hunt and J. Varigos and A. Avezum and L. Piegas and C. Joyner and P. Theroux and H. Rupprecht and T. Wittlinger and N. Karatzasy and M. Keltai and E. Sitkei and D. Halon and Lewis, {B. S.} and Franzosi, {M. G.} and M. Galli and A. Maggioni and F. Mauri and M. Ramos-Corrales and A. Budaj and L. Ceremuzynski and P. Commerford and M. Flather and J. Anderson and J. Hirsh and J. Cairns and M. Gent and R. Gorlin and J. Willerson and J. Wittes and G. Wyse and P. Auger and Chan, {Y. K.} and H. Hernandez and M. Kyriakidis and Marquis, {J. F.} and B. Mayosi and S. Mehta and M. Natarajan and A. Panju and E. Paolasso and C. Rihal and B. Sussex and W. Wasek and B. Cracknell and J. Lindeman and J. Mackay and H. Marsh and M. Anderson and M. Sloan and I. Stoica and J. Tucker and F. Cherian and C. Christmas and C. Cuvay and I. Holadyk-Gris and S. Kotlan and F. Mazur and M. Micks and K. Nair and L. Robinson and S. Seitz and S. Smith and L. Tomic and A. Gafni and A. Lamy and J. Pogue and C. Sigouin and J. Brown and L. Cronin and M. Johnston and J. Weitz",
year = "2001",
doi = "10.1016/S0735-1097(00)01118-9",
language = "English (US)",
volume = "37",
pages = "475--484",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "2",

}

TY - JOUR

T1 - Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina

AU - Yusuf, S.

AU - Pogue, J.

AU - Anand, S.

AU - Tognoni, G.

AU - Fox, K.

AU - Díaz, R.

AU - Paolasso, E.

AU - Hunt, D.

AU - Varigos, J.

AU - Avezum, A.

AU - Piegas, L.

AU - Joyner, C.

AU - Theroux, P.

AU - Rupprecht, H.

AU - Wittlinger, T.

AU - Karatzasy, N.

AU - Keltai, M.

AU - Sitkei, E.

AU - Halon, D.

AU - Lewis, B. S.

AU - Franzosi, M. G.

AU - Galli, M.

AU - Maggioni, A.

AU - Mauri, F.

AU - Ramos-Corrales, M.

AU - Budaj, A.

AU - Ceremuzynski, L.

AU - Commerford, P.

AU - Flather, M.

AU - Anderson, J.

AU - Hirsh, J.

AU - Cairns, J.

AU - Gent, M.

AU - Gorlin, R.

AU - Willerson, J.

AU - Wittes, J.

AU - Wyse, G.

AU - Auger, P.

AU - Chan, Y. K.

AU - Hernandez, H.

AU - Kyriakidis, M.

AU - Marquis, J. F.

AU - Mayosi, B.

AU - Mehta, S.

AU - Natarajan, M.

AU - Panju, A.

AU - Paolasso, E.

AU - Rihal, C.

AU - Sussex, B.

AU - Wasek, W.

AU - Cracknell, B.

AU - Lindeman, J.

AU - Mackay, J.

AU - Marsh, H.

AU - Anderson, M.

AU - Sloan, M.

AU - Stoica, I.

AU - Tucker, J.

AU - Cherian, F.

AU - Christmas, C.

AU - Cuvay, C.

AU - Holadyk-Gris, I.

AU - Kotlan, S.

AU - Mazur, F.

AU - Micks, M.

AU - Nair, K.

AU - Robinson, L.

AU - Seitz, S.

AU - Smith, S.

AU - Tomic, L.

AU - Gafni, A.

AU - Lamy, A.

AU - Pogue, J.

AU - Sigouin, C.

AU - Brown, J.

AU - Cronin, L.

AU - Johnston, M.

AU - Weitz, J.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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