Apixaban with antiplatelet therapy after acute coronary syndrome

John H. Alexander, Renato D. Lopes, Stefan James, Rakhi Kilaru, Yaohua He, Puneet Mohan, Deepak L. Bhatt, Shaun Goodman, Freek W. Verheugt, Marcus Flather, Kurt Huber, Danny Liaw, Steen E. Husted, Jose Lopez-Sendon, Raffaele De Caterina, Petr Jansky, Harald Darius, Dragos Vinereanu, Jan H. Cornel, Frank Cools & 14 others Dan Atar, Jose Luis Leiva-Pons, M. Keltai, Hisao Ogawa, Prem Pais, Alexander Parkhomenko, Witold Ruzyllo, Rafael Diaz, Harvey White, Mikhail Ruda, Margarida Geraldes, Jack Lawrence, Robert A. Harrington, Lars Wallentin

Research output: Contribution to journalArticle

727 Citations (Scopus)

Abstract

BACKGROUND: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. RESULTS: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. CONCLUSIONS: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.)

Original languageEnglish
Pages (from-to)699-708
Number of pages10
JournalNew England Journal of Medicine
Volume365
Issue number8
DOIs
Publication statusPublished - Aug 25 2011

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Acute Coronary Syndrome
Placebos
Hemorrhage
Therapeutics
Myocardial Infarction
apixaban
Confidence Intervals
Controlled Clinical Trials
Patient Selection
Stroke
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Alexander, J. H., Lopes, R. D., James, S., Kilaru, R., He, Y., Mohan, P., ... Wallentin, L. (2011). Apixaban with antiplatelet therapy after acute coronary syndrome. New England Journal of Medicine, 365(8), 699-708. https://doi.org/10.1056/NEJMoa1105819

Apixaban with antiplatelet therapy after acute coronary syndrome. / Alexander, John H.; Lopes, Renato D.; James, Stefan; Kilaru, Rakhi; He, Yaohua; Mohan, Puneet; Bhatt, Deepak L.; Goodman, Shaun; Verheugt, Freek W.; Flather, Marcus; Huber, Kurt; Liaw, Danny; Husted, Steen E.; Lopez-Sendon, Jose; De Caterina, Raffaele; Jansky, Petr; Darius, Harald; Vinereanu, Dragos; Cornel, Jan H.; Cools, Frank; Atar, Dan; Leiva-Pons, Jose Luis; Keltai, M.; Ogawa, Hisao; Pais, Prem; Parkhomenko, Alexander; Ruzyllo, Witold; Diaz, Rafael; White, Harvey; Ruda, Mikhail; Geraldes, Margarida; Lawrence, Jack; Harrington, Robert A.; Wallentin, Lars.

In: New England Journal of Medicine, Vol. 365, No. 8, 25.08.2011, p. 699-708.

Research output: Contribution to journalArticle

Alexander, JH, Lopes, RD, James, S, Kilaru, R, He, Y, Mohan, P, Bhatt, DL, Goodman, S, Verheugt, FW, Flather, M, Huber, K, Liaw, D, Husted, SE, Lopez-Sendon, J, De Caterina, R, Jansky, P, Darius, H, Vinereanu, D, Cornel, JH, Cools, F, Atar, D, Leiva-Pons, JL, Keltai, M, Ogawa, H, Pais, P, Parkhomenko, A, Ruzyllo, W, Diaz, R, White, H, Ruda, M, Geraldes, M, Lawrence, J, Harrington, RA & Wallentin, L 2011, 'Apixaban with antiplatelet therapy after acute coronary syndrome', New England Journal of Medicine, vol. 365, no. 8, pp. 699-708. https://doi.org/10.1056/NEJMoa1105819
Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P et al. Apixaban with antiplatelet therapy after acute coronary syndrome. New England Journal of Medicine. 2011 Aug 25;365(8):699-708. https://doi.org/10.1056/NEJMoa1105819
Alexander, John H. ; Lopes, Renato D. ; James, Stefan ; Kilaru, Rakhi ; He, Yaohua ; Mohan, Puneet ; Bhatt, Deepak L. ; Goodman, Shaun ; Verheugt, Freek W. ; Flather, Marcus ; Huber, Kurt ; Liaw, Danny ; Husted, Steen E. ; Lopez-Sendon, Jose ; De Caterina, Raffaele ; Jansky, Petr ; Darius, Harald ; Vinereanu, Dragos ; Cornel, Jan H. ; Cools, Frank ; Atar, Dan ; Leiva-Pons, Jose Luis ; Keltai, M. ; Ogawa, Hisao ; Pais, Prem ; Parkhomenko, Alexander ; Ruzyllo, Witold ; Diaz, Rafael ; White, Harvey ; Ruda, Mikhail ; Geraldes, Margarida ; Lawrence, Jack ; Harrington, Robert A. ; Wallentin, Lars. / Apixaban with antiplatelet therapy after acute coronary syndrome. In: New England Journal of Medicine. 2011 ; Vol. 365, No. 8. pp. 699-708.
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abstract = "BACKGROUND: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. RESULTS: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5{\%}) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9{\%}) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95{\%} confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3{\%}) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5{\%}) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95{\%} CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. CONCLUSIONS: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.)",
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T1 - Apixaban with antiplatelet therapy after acute coronary syndrome

AU - Alexander, John H.

AU - Lopes, Renato D.

AU - James, Stefan

AU - Kilaru, Rakhi

AU - He, Yaohua

AU - Mohan, Puneet

AU - Bhatt, Deepak L.

AU - Goodman, Shaun

AU - Verheugt, Freek W.

AU - Flather, Marcus

AU - Huber, Kurt

AU - Liaw, Danny

AU - Husted, Steen E.

AU - Lopez-Sendon, Jose

AU - De Caterina, Raffaele

AU - Jansky, Petr

AU - Darius, Harald

AU - Vinereanu, Dragos

AU - Cornel, Jan H.

AU - Cools, Frank

AU - Atar, Dan

AU - Leiva-Pons, Jose Luis

AU - Keltai, M.

AU - Ogawa, Hisao

AU - Pais, Prem

AU - Parkhomenko, Alexander

AU - Ruzyllo, Witold

AU - Diaz, Rafael

AU - White, Harvey

AU - Ruda, Mikhail

AU - Geraldes, Margarida

AU - Lawrence, Jack

AU - Harrington, Robert A.

AU - Wallentin, Lars

PY - 2011/8/25

Y1 - 2011/8/25

N2 - BACKGROUND: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. RESULTS: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. CONCLUSIONS: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.)

AB - BACKGROUND: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. RESULTS: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. CONCLUSIONS: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.)

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