Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke
Ralph L. Sacco, M.D., Hans-Christoph Diener, M.D., Ph.D., Salim Yusuf, M.B., B.S., D.Phil., Daniel Cotton, M.S., Stephanie Ôunpuu, Ph.D., William A. Lawton, B.A., Yuko Palesch, Ph.D., Reneé H. Martin, Ph.D., Gregory W. Albers, M.D., Philip Bath, F.R.C.P., Natan Bornstein, M.D., Bernard P.L. Chan, M.D., Sien-Tsong Chen, M.D., Luis Cunha, M.D., Ph.D., Björn Dahlöf, M.D., Ph.D., Jacques De Keyser, M.D., Ph.D., Geoffrey A. Donnan, M.D., Conrado Estol, M.D., Ph.D., Philip Gorelick, M.D., Vivian Gu, M.D., Karin Hermansson, D.M.Sc., Lutz Hilbrich, M.D., Markku Kaste, M.D., Ph.D., Chuanzhen Lu, M.D., Thomas Machnig, M.D., Prem Pais, M.D., Robin Roberts, M.Tech., Veronika Skvortsova, M.D., Philip Teal, M.D., Danilo Toni, M.D., Cam VanderMaelen, Ph.D., Thor Voigt, M.D., Michael Weber, M.D., Byung-Woo Yoon, M.D., Ph.D., for the PRoFESS Study Group
Background Recurrent stroke is a frequent, disabling event afterischemic stroke. This study compared the efficacy and safetyof two antiplatelet regimens — aspirin plus extended-releasedipyridamole (ASA–ERDP) versus clopidogrel.
Methods In this double-blind, 2-by-2 factorial trial, we randomlyassigned patients to receive 25 mg of aspirin plus 200 mg ofextended-release dipyridamole twice daily or to receive 75 mgof clopidogrel daily. The primary outcome was first recurrenceof stroke. The secondary outcome was a composite of stroke,myocardial infarction, or death from vascular causes. Sequentialstatistical testing of noninferiority (margin of 1.075), followedby superiority testing, was planned.
Results A total of 20,332 patients were followed for a meanof 2.5 years. Recurrent stroke occurred in 916 patients (9.0%)receiving ASA–ERDP and in 898 patients (8.8%) receivingclopidogrel (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 eventsamong ASA–ERDP recipients (419 [4.1%]) than among clopidogrelrecipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to1.32), including intracranial hemorrhage (hazard ratio, 1.42;95% CI, 1.11 to 1.83). The net risk of recurrent stroke or majorhemorrhagic event was similar in the two groups (1194 ASA–ERDPrecipients [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 fornoninferiority but showed similar rates of recurrent strokewith ASA–ERDP and with clopidogrel. There is no evidencethat either of the two treatments was superior to the otherin the prevention of recurrent stroke. (ClinicalTrials.gov number,NCT00153062
[ClinicalTrials.gov]
.)
Source Information
The authors' affiliations are listed in the Appendix. Drs. Sacco, Diener, and Yusuf contributed equally to this article. This article (10.1056/NEJMoa0805002) was published at www.nejm.org on August 27, 2008.
Address reprint requests to Dr. Sacco at the Miller School of Medicine, University of Miami, Clinical Research Building, 1120 NW 14th St., Suite 1353, Miami, FL 33136, or at rsacco{at}med.miami.edu.
Gurbel, P. A., Tantry, U. S.
(2010). Combination Antithrombotic Therapies. Circulation
121: 569-583
[Full Text]
Seet, R. C.-S., Chen, C. P.L.
(2009). Optimizing Antiplatelet Therapy in High-Risk Patients With Atrial Fibrillation: Insights From Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A). Stroke
40: 3883-3885
[Full Text]
Bath, P. M. W., Martin, R. H., Palesch, Y., Cotton, D., Yusuf, S., Sacco, R., Diener, H.-C., Toni, D., Estol, C., Roberts, R., for the PRoFESS Study Group,
(2009). Effect of Telmisartan on Functional Outcome, Recurrence, and Blood Pressure in Patients With Acute Mild Ischemic Stroke: A PRoFESS Subgroup Analysis. Stroke
40: 3541-3546
[Abstract][Full Text]
Giannakopoulos, B., Krilis, S. A.
(2009). How I treat the antiphospholipid syndrome. Blood
114: 2020-2030
[Abstract][Full Text]
Maasland, L., van Oostenbrugge, R. J., Franke, C. F., Scholte op Reimer, W. J.M., Koudstaal, P. J., Dippel, D. W.J., for the Netherlands Stroke Survey Investigators,
(2009). Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice: The Netherlands Stroke Survey. Stroke
40: 2662-2668
[Abstract][Full Text]
Kirchhof, P., Bax, J., Blomstrom-Lundquist, C., Calkins, H., Camm, A. J., Cappato, R., Cosio, F., Crijns, H., Diener, H.-C., Goette, A., Israel, C. W., Kuck, K.-H., Lip, G. Y.H., Nattel, S., Page, R. L., Ravens, U., Schotten, U., Steinbeck, G., Vardas, P., Waldo, A., Wegscheider, K., Willems, S., Breithardt, G.
(2009). Early and comprehensive management of atrial fibrillation: Proceedings from the 2nd AFNET/EHRA consensus conference on atrial fibrillation entitled 'research perspectives in atrial fibrillation'. Europace
11: 860-885
[Full Text]
Armario, P., de la Sierra, A.
(2009). Antihypertensive treatment and stroke prevention: are angiotensin receptor blockers superior to other antihypertensive agents?. Ther Adv Cardiovasc Dis
3: 197-204
[Abstract]
Turan, T. N., Derdeyn, C. P., Fiorella, D., Chimowitz, M. I.
(2009). Treatment of Atherosclerotic Intracranial Arterial Stenosis. Stroke
40: 2257-2261
[Full Text]
Tousoulis, D., Briasoulis, A., Dhamrait, S. S, Antoniades, C., Stefanadis, C.
(2009). Effective platelet inhibition by aspirin and clopidogrel: where are we now?. Heart
95: 850-858
[Full Text]
Algra, A.
(2009). Digestion of the Antiplatelets Comparison of PRoFESS: 18-7=1?. Stroke
40: 1932-1935
[Full Text]
Selim, M.
(2009). Antiplatelets for Stroke Prevention: Implications of the PRoFESS Trial. Stroke
40: 1936-1937
[Full Text]
Higgins, P., Lees, K. R.
(2009). Advances in Emerging Therapies. Stroke
40: e292-e294
[Full Text]
Sanz, J., Moreno, P. R., Fuster, V.
(2009). The Year in Atherothrombosis. J Am Coll Cardiol
53: 1326-1337
[Full Text]
Josephson, C. B, Salman, R. A.-S., Phillips, S. J
(2009). An episode of transient neurological symptoms. BMJ
338: b616-b616
[Full Text]
Cohen, M.
(2009). Expanding the Recognition and Assessment of Bleeding Events Associated With Antiplatelet Therapy in Primary Care. Mayo Clin Proc.
84: 149-160
[Abstract][Full Text]
Cucchiara, B. L.
(2009). Evaluation and management of stroke. ASH Education Book
2009: 293-301
[Abstract][Full Text]
Adams, H. P. Jr
(2009). Secondary Prevention of Atherothrombotic Events After Ischemic Stroke. Mayo Clin Proc.
84: 43-51
[Abstract][Full Text]
Diener, H.-C., Mattle, H., Böhm, M., Ruschitzka, F.
(2009). CHAPTER 15a The Heart and the Brain. ESC Textbook of Cardiovascular Medicine
2: med-9780199566990-chapter-med-9780199566990-chapter
[Abstract][Full Text]
Bayley, M. MD, Lindsay, P. BScN PhD, Hellings, C. BScH, Woodbury, E. BCom MHA, Phillips, S. MBBS, on behalf of the Canadian Stroke Strategy (a joint,
(2008). Balancing evidence and opinion in stroke care: the 2008 best practice recommendations. CMAJ
179: 1247-1249
[Full Text]
(2008). Antiplatelet Agents to Prevent Recurrent Stroke. JWatch Oncology and Hematology
2008: 2-2
[Full Text]
Kent, D. M., Thaler, D. E.
(2008). Stroke Prevention -- Insights from Incoherence. NEJM
359: 1287-1289
[Full Text]
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