Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Ralph L Sacco, Hans Christoph Diener, Salim Yusuf, Daniel Cotton, Stephanie Ôunpuu, William A. Lawton, Yuko Palesch, Reneé H. Martin, Gregory W. Albers, Philip Bath, Natan Bornstein, Bernard P L Chan, Sien Tsong Chen, Luis Cunha, Björn Dahlöf, Jacques De Keyser, Geoffrey A. Donnan, Conrado Estol, Philip Gorelick, Vivian GuKarin Hermansson, Lutz Hilbrich, Markku Kaste, Chuanzhen Lu, Thomas Machnig, Prem Pais, Robin Roberts, Veronika Skvortsova, Philip Teal, Danilo Toni, Cam Vander Maelen, Thor Voigt, Michael Weber, Byung Woo Yoon

Research output: Contribution to journalArticle

688 Citations (Scopus)

Abstract

BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens - aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke.

Original languageEnglish
Pages (from-to)1238-1251
Number of pages14
JournalNew England Journal of Medicine
Volume359
Issue number12
DOIs
StatePublished - Sep 18 2008

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clopidogrel
Stroke
Confidence Intervals
Dipyridamole
Dipyridamole Drug Combination Aspirin
Intracranial Hemorrhages
Aspirin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sacco, R. L., Diener, H. C., Yusuf, S., Cotton, D., Ôunpuu, S., Lawton, W. A., ... Yoon, B. W. (2008). Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. New England Journal of Medicine, 359(12), 1238-1251. https://doi.org/10.1056/NEJMoa0805002

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. / Sacco, Ralph L; Diener, Hans Christoph; Yusuf, Salim; Cotton, Daniel; Ôunpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Reneé H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; Vander Maelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung Woo.

In: New England Journal of Medicine, Vol. 359, No. 12, 18.09.2008, p. 1238-1251.

Research output: Contribution to journalArticle

Sacco, RL, Diener, HC, Yusuf, S, Cotton, D, Ôunpuu, S, Lawton, WA, Palesch, Y, Martin, RH, Albers, GW, Bath, P, Bornstein, N, Chan, BPL, Chen, ST, Cunha, L, Dahlöf, B, De Keyser, J, Donnan, GA, Estol, C, Gorelick, P, Gu, V, Hermansson, K, Hilbrich, L, Kaste, M, Lu, C, Machnig, T, Pais, P, Roberts, R, Skvortsova, V, Teal, P, Toni, D, Vander Maelen, C, Voigt, T, Weber, M & Yoon, BW 2008, 'Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke', New England Journal of Medicine, vol. 359, no. 12, pp. 1238-1251. https://doi.org/10.1056/NEJMoa0805002
Sacco, Ralph L ; Diener, Hans Christoph ; Yusuf, Salim ; Cotton, Daniel ; Ôunpuu, Stephanie ; Lawton, William A. ; Palesch, Yuko ; Martin, Reneé H. ; Albers, Gregory W. ; Bath, Philip ; Bornstein, Natan ; Chan, Bernard P L ; Chen, Sien Tsong ; Cunha, Luis ; Dahlöf, Björn ; De Keyser, Jacques ; Donnan, Geoffrey A. ; Estol, Conrado ; Gorelick, Philip ; Gu, Vivian ; Hermansson, Karin ; Hilbrich, Lutz ; Kaste, Markku ; Lu, Chuanzhen ; Machnig, Thomas ; Pais, Prem ; Roberts, Robin ; Skvortsova, Veronika ; Teal, Philip ; Toni, Danilo ; Vander Maelen, Cam ; Voigt, Thor ; Weber, Michael ; Yoon, Byung Woo. / Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. In: New England Journal of Medicine. 2008 ; Vol. 359, No. 12. pp. 1238-1251.
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abstract = "BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens - aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0{\%}) receiving ASA-ERDP and in 898 patients (8.8{\%}) receiving clopidogrel (hazard ratio, 1.01; 95{\%} confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1{\%}) in each group (hazard ratio for ASA-ERDP, 0.99; 95{\%} CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1{\%}]) than among clopidogrel recipients (365 [3.6{\%}]) (hazard ratio, 1.15; 95{\%} CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95{\%} CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7{\%}], vs. 1156 clopidogrel recipients [11.4{\%}]; hazard ratio, 1.03; 95{\%} CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke.",
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T1 - Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

AU - Sacco, Ralph L

AU - Diener, Hans Christoph

AU - Yusuf, Salim

AU - Cotton, Daniel

AU - Ôunpuu, Stephanie

AU - Lawton, William A.

AU - Palesch, Yuko

AU - Martin, Reneé H.

AU - Albers, Gregory W.

AU - Bath, Philip

AU - Bornstein, Natan

AU - Chan, Bernard P L

AU - Chen, Sien Tsong

AU - Cunha, Luis

AU - Dahlöf, Björn

AU - De Keyser, Jacques

AU - Donnan, Geoffrey A.

AU - Estol, Conrado

AU - Gorelick, Philip

AU - Gu, Vivian

AU - Hermansson, Karin

AU - Hilbrich, Lutz

AU - Kaste, Markku

AU - Lu, Chuanzhen

AU - Machnig, Thomas

AU - Pais, Prem

AU - Roberts, Robin

AU - Skvortsova, Veronika

AU - Teal, Philip

AU - Toni, Danilo

AU - Vander Maelen, Cam

AU - Voigt, Thor

AU - Weber, Michael

AU - Yoon, Byung Woo

PY - 2008/9/18

Y1 - 2008/9/18

N2 - BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens - aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke.

AB - BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens - aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke.

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