Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study.

Hans-Christoph Diener (1) , Ralph L Sacco (2) , Salim Yusuf (3) , Daniel Cotton (4) , Stephanie Ounpuu (5) , William A Lawton (6) , Yuko Palesch (7) , Reneé H Martin (7) , Gregory W Albers (8) , Philip Bath (9) , Natan Bornstein (10) , Bernard P L Chan (11) , Sien-Tsong Chen (12) , Luis Cunha (13) , Björn Dahlöf (14) , Jacques de Keyser (15) , Geoffrey A Donnan (16) , Conrado Estol (17) , Philip Gorelick (18) , Vivian Gu (19) , Karin Hermansson (20) , Lutz Hilbrich (4) , Markku Kaste (21) , Chuanzhen Lu (22) , Thomas Machnig (23) , Prem Pais (24) , Robin Roberts (25) , Veronika Skvortsova (26) , Philip Teal (27) , Danilo Toni (28) , Cam Vandermaelen (4) , Thor Voigt (4) , Michael Weber (29) , Byung-Woo Yoon (30) , Francisco Macian-Montoro (31, 32) , Group Prevention Regimen For Effectively Avoiding Second Strokes (profess) Study

1 Department of neurology
2 Department of neurology
3 Population Health Research Institute
4 Boehringer Ingelheim Pharmaceuticals
5 Boehringer Ingelheim
6 Boehringer Ingelheim Ltd
7 Department of biostatistics, Bioinformatics and Epidemiology
8 Neurology and Neurological Sciences
9 Stroke Trials Unit
10 Neurology Department
11 Division of Neurology, Department of Medicine
12 Department of Neurology
13 Neurology department
14 Institute of Medicine
15 Department of neurology
16 National Stroke Research Institute
17 Neurological Center for Treatment and Research
18 Department of Neurology and Rehabilitation
19 Boehringer Ingelheim Shanghai Pharmaceuticals Co Ltd
20 Boehringer Ingelheim AB
21 Department of Neurology
22 Neurology Department
23 Boehringer Ingelheim GmbH
24 Saint John's Medical College
25 Clinical Trials Methodoloy Group
26 Neurology & Neurosurgery Clinic
27 Department of Medicine, Neurology, Faculty of Medicine
28 Department of Neurological Sciences
29 Cardiology Department
30 Department of Neurology
31 Service de Neurologie [CHU Limoges]
32 NETEC - Neuroépidémiologie Tropicale et Comparée

BACKGROUND: The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062. FINDINGS: 20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. INTERPRETATION: Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

Domaines: Neurosciences [q-bio.NC]; Santé publique et épidémiologie

Hans-Christoph Diener, Ralph L Sacco, Salim Yusuf, Daniel Cotton, Stephanie Ounpuu, et al.. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study.. The Lancet Neurology, 2008, 7 (10), pp.875-84. ⟨10.1016/S1474-4422(08)70198-4⟩. ⟨hal-00627064⟩