Original Article
Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke
N Engl J Med 2008; 359:1238-1251September 18, 2008
- 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. (ClinicalTrials.gov number, NCT00153062.)
Media in This Article
Figure 1
Kaplan–Meier Estimates of the Cumulative Probability of Primary and Secondary Outcomes, According to Treatment Group.Figure 2
Frequency of Types of Recurrent Stroke among the Study Patients, According to Treatment Group.Article Activity
- Article
Recurrent stroke is an important vascular event affecting the life of survivors of ischemic stroke.1 Multiple randomized trials have proved the efficacy of antiplatelet agents for the prevention of recurrent stroke after noncardioembolic stroke.2-11 Antiplatelet options for the prevention of recurrent stroke include aspirin (50 mg to 325 mg per day), the combination of low-dose aspirin and extended-release dipyridamole, and clopidogrel alone.12,13
Aspirin has been shown to reduce the risk of stroke recurrence by about 23% as compared with placebo.7 Studies of clopidogrel have suggested an 8% relative risk reduction of stroke recurrence, as compared with aspirin, among stroke patients, whereas studies of aspirin plus extended-release dipyridamole have suggested relative risk reductions of 20 to 23% as compared with aspirin alone.4,5,10,11 Indirect comparisons suggested that aspirin plus extended-release dipyridamole was superior to clopidogrel in the prevention of recurrent stroke.14
Although the combination of two antiplatelet agents with different mechanisms of action may be more effective in preventing recurrent stroke than either is alone, increased bleeding may result. Two trials have shown that the combination of aspirin and extended-release dipyridamole is better than aspirin alone for prevention of recurrent stroke — as well as stroke, myocardial infarction, and death from vascular causes — without increasing the risk of major bleeding.5,10,11 Among stroke patients with multiple risk factors, the addition of aspirin to clopidogrel is not more efficacious than clopidogrel alone but significantly increases the incidence of bleeding.8 Moderate bleeding is increased with the use of clopidogrel and aspirin, as compared with aspirin alone, in secondary and primary prevention.15,16
There is no guideline for using one of these therapies over the other.12,17 Thus, in this trial, we aimed to compare the relative efficacy and safety of aspirin plus extended-release dipyridamole with that of clopidogrel among patients who had a recent ischemic stroke.18
Methods
The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial was a 2-by-2 factorial, double-blind, active and placebo-controlled study of the fixed combination of low-dose aspirin (25 mg) and extended-release dipyridamole (200 mg) given twice daily as compared with clopidogrel (75 mg) given once daily, and of telmisartan (80 mg once daily) as compared with placebo, in patients with a recent ischemic stroke. This article focuses on the antiplatelet comparison within the factorial design. The antiplatelet part of the factorial design was initially intended to compare clopidogrel plus aspirin with aspirin plus extended-release dipyridamole. The design was modified, after 2027 patients were randomly assigned, when the Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent TIA or Ischemic Stroke (MATCH) trial demonstrated an increased risk of bleeding with the combination of clopidogrel and aspirin.8 Patients initially assigned to receive clopidogrel plus aspirin had been treated for up to 8 months before they were switched to clopidogrel alone at the time of the protocol amendment; 18,305 patients were subsequently randomly assigned to receive aspirin plus extended-release dipyridamole or clopidogrel alone.
Details of the trial design have been published previously.18 The steering committee designed and oversaw the trial; data management was performed by the sponsor (Boehringer Ingelheim). A trial management committee, with representatives from the steering committee and the sponsor, met regularly to evaluate progress. The cochairs and the members of the steering committee had complete access to the trial data and prepared the final manuscript, and they vouch for the design, the final statistical analysis, and the completeness, accuracy, and interpretation of the data. The final statistical analyses were conducted simultaneously by the independent statisticians at the Medical University of South Carolina (who provided data and interim analysis reports to the data and safety monitoring committee) and the statisticians from Boehringer Ingelheim.
The protocol was approved by the appropriate regulatory authorities and ethics committees or institutional review boards. All patients provided written informed consent.
Eligibility
The inclusion criteria were a recent ischemic stroke (within <90 days before randomization), defined by symptoms persisting for more than 24 hours or symptoms of a shorter duration but with evidence of a recent brain infarction on a computed tomographic scan or magnetic resonance imaging; clinical and neurologic stability before randomization; and an age of 55 years or older. Patients were excluded if they had contraindications to one of the antiplatelet agents or were otherwise unsuitable for randomization.18 After approximately 6000 patients had been enrolled, a protocol amendment was introduced to enhance recruitment and permit the inclusion of younger patients (50 to 54 years of age) or those with less recent strokes (within 90 to 120 days before randomization) if they also had at least two additional vascular risk factors.18
Randomization and Treatment
Eligible and consenting patients were randomly assigned, through a central telephone randomization system, to receive either aspirin (25 mg) plus extended-release dipyridamole (200 mg) twice daily or clopidogrel (75 mg daily) and telmisartan (80 mg daily) or placebo. Patients were evaluated in the hospital at the time of discharge or at 1 week after discharge and then at 1, 3, and 6 months and every 6 months thereafter.
Outcome Events
The primary outcome was recurrent stroke of any type. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. The tertiary outcomes are listed in the Supplementary Appendix (available with the full text of this article at www.nejm.org). The primary and secondary outcomes, and episodes of major bleeding, were adjudicated by a central committee. If a patient had a recurrence of ischemic stroke, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria were used to classify the event.19 Three months after the recurrence of stroke, the degree of disability was assessed according to the modified Rankin scale (with scores ranging from 0 to 6 and higher scores indicating greater disability) and the Barthel index (with scores ranging from 0 to 100 and higher scores indicating less disability).20,21 Definitions for hemorrhagic events (major, life-threatening, intracranial, and minor) are listed in the Supplementary Appendix.
Data Monitoring
An independent data and safety monitoring committee regularly monitored the safety and quality of the data of the trial. Two formal interim efficacy analyses were performed with the use of modified Haybittle–Peto22 boundaries to test the null hypotheses of no difference between treatment groups, with thresholds of P<0.0001 when one third of expected events had occurred and P<0.001 when two thirds of the expected events had occurred.
Statistical Analysis
This event-driven trial was originally designed to test the superiority of aspirin plus extended-release dipyridamole over clopidogrel in 15,500 patients, modified to 20,000 patients after six protocol amendments owing to lower-than-expected numbers of primary outcome events. With this amended sample size, the trial had a statistical power of 82% to detect a 13% relative risk reduction after 1715 strokes had occurred.
A sequential analysis for the antiplatelet comparison was developed and planned to first test the noninferiority of aspirin plus extended-release dipyridamole as compared with clopidogrel. If this condition was satisfied, then the superiority of aspirin plus extended-release dipyridamole over clopidogrel could be assessed in a second test of the conventional null hypothesis of no difference between the two treatments.
Confirmation of noninferiority in this trial involved the prespecification of a hazard ratio for aspirin plus extended-release dipyridamole, as compared with clopidogrel, that is below a predefined margin. The margin was defined in the following way. Using data from the nonfatal stroke outcomes from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial4 and from the meta-analysis by the Antithrombotic Trialists' Collaboration,7 and following the method of Fisher et al.,23 we derived an estimated odds ratio for clopidogrel being better than placebo for the outcome of nonfatal stroke: 1.377 (95% confidence interval [CI], 1.155 to 1.645). Thus, to ensure that the aspirin plus extended-release dipyridamole preserved at least half the effect of clopidogrel, the noninferiority margin was set at 1.075, an effect size equal to half the lower limit of the confidence interval. To reject the inferiority null hypothesis, the upper boundary of the 95% confidence interval for the hazard ratio must lie below the value of 1.075 (an increase of 7.5% in the hazard associated with aspirin plus extended-release dipyridamole). With 1715 recurrent strokes, we would have a statistical power of 82% to reject the inferiority null hypothesis, assuming a 6.5% relative risk reduction with aspirin plus extended-release dipyridamole as compared with clopidogrel.
The primary analysis was of the time to the first recurrence of stroke. The Cox proportional-hazards regression model was prespecified for analysis of this outcome and had as covariates the baseline values for age, diabetes status, use or nonuse of angiotensin-converting–enzyme inhibitors, and score on the modified Rankin scale. Before conducting the antiplatelet comparison, on the basis of data aggregated across the telmisartan and placebo groups, we performed a test of interaction (with a prespecified alpha value of 1%). The antiplatelet noninferiority comparison was then conducted with a one-sided alpha value of 2.5%; the test of superiority was two-sided with an alpha value of 5%. All analyses were performed according to the intention-to-treat principle, involved a time-to event approach, and included all randomized patients.
Subgroup analyses for the primary outcome and for major vascular events were performed for prespecified baseline features. These included a history of vascular disease, alcohol use, and a stroke risk score generated from the overall trial data (i.e., age, sex, degree of physical activity, baseline systolic blood pressure, and history of hypertension, diabetes, myocardial infarction, atrial fibrillation, peripheral arterial disease, and stroke before the qualifying event).
Results
A total of 20,333 patients were enrolled from 695 centers in 35 countries. One patient who did not give written informed consent was randomized in error but never received a study drug or underwent follow-up and was not included in the study database. Therefore, the data are reported for 20,332 patients: 10,181 recipients of aspirin plus extended-release dipyridamole and 10,151 recipients of clopidogrel. The trial commenced on September 11, 2003, and patients were followed until the end of the trial on February 8, 2008. The mean duration of follow-up was 2.5 years (range, 1.5 to 4.4); 1495 patients (7.4%) died during the study and 125 patients (0.6% in each treatment group) were lost to follow-up.
Baseline characteristics were balanced across the two treatment groups (Table 1Table 1
Baseline Characteristics of the Two Treatment Groups.). The mean age was 66.1 years, and 36.0% were women. Almost one quarter of the patients had a history of stroke or transient ischemic attack before the index stroke; 74.0% had a history of hypertension, 46.7% of dyslipidemia, 28.2% of diabetes, and 16.3% of ischemic coronary artery disease. The median time from the qualifying stroke to randomization was 15 days, and 39.8% of patients were randomized within 10 days after that event. The most frequent type of ischemic stroke was small-artery occlusion (lacune), in 52.0% of patients, whereas 28.6% had large-artery atherosclerosis.Premature discontinuation of the study drug was significantly more frequent among patients receiving aspirin plus extended-release dipyridamole (2961 patients [29.1%]) than among those receiving clopidogrel (2290 [22.6%], P<0.001). Medication compliance, defined as taking the study medication more than 75% of the time, was greater in the clopidogrel group (76.8%) than in the group receiving aspirin and extended-release dipyridamole (69.6%).
Primary Outcome
Confirmed first recurrence of stroke occurred in 1814 patients. There was no interaction between the treatment benefit of the antiplatelet treatment and telmisartan (P=0.35). The primary outcome of first recurrence of stroke occurred in 916 recipients (9.0%) of aspirin plus extended-release dipyridamole and 898 recipients (8.8%) of clopidogrel (hazard ratio, 1.01; 95% CI, 0.92 to 1.11) (Table 2Table 2
Hazard Ratios for Primary, Secondary, and Key Tertiary Efficacy and Safety Outcomes. and Figure 1AFigure 1Kaplan–Meier Estimates of the Cumulative Probability of Primary and Secondary Outcomes, According to Treatment Group.). Although the hazard ratio is very close to 1.00 (representing equivalence), the upper limit of the confidence interval extends beyond the prespecified noninferiority margin of 1.075.Ischemic stroke accounted for 87.4% (1585 of 1814) of the recurrent strokes (Figure 2Figure 2
Frequency of Types of Recurrent Stroke among the Study Patients, According to Treatment Group.). Although there were 25 fewer ischemic recurrent strokes in the group receiving aspirin plus extended-release dipyridamole than in the group receiving clopidogrel, recipients of aspirin and extended-release dipyridamole had 5 more recurrent strokes of other or unknown causes and 38 more hemorrhagic strokes. Despite this excess of hemorrhagic strokes, the number of patients with fatal or disabling strokes (defined by a score of ≥3 on the modified Rankin scale at 3 months after the recurrence of stroke) was similar in the two groups: 413 (4.1%) in the aspirin–extended-release dipyridamole group and 392 (3.9%) in the clopidogrel group (hazard ratio, 1.05; 95% CI, 0.96 to 1.16). In analyses based on the treatment received, the results for the primary outcome were virtually the same in the two groups, with recurrent stroke occurring in 777 patients (7.6%) receiving aspirin plus extended-release dipyridamole and in 777 patients (7.7%) receiving clopidogrel (hazard ratio, 1.07; 95% CI, 0.97 to 1.18).Secondary and Tertiary Outcomes
The numbers of patients with the secondary outcome of stroke, myocardial infarction, or death from vascular causes were identical in the two groups: 1333 patients (13.1%) (hazard ratio for aspirin plus extended-release dipyridamole vs. clopidogrel, 0.99; 95% CI, 0.92 to 1.07) (Table 2 and Figure 1B). The rates of most tertiary (efficacy) outcomes were similar in the two groups (Table 2). The rate of new or worsening congestive heart failure was significantly lower in the group receiving aspirin plus extended-release dipyridamole (144 patients [1.4%]) than in the group receiving clopidogrel (182 patients [1.8%]; hazard ratio, 0.78; 95% CI, 0.62 to 0.96). There was no significant difference in the rate of recurrent stroke or major hemorrhagic event between the recipients of aspirin plus extended-release dipyridamole (1194 [11.7%]) and the recipients of clopidogrel (1156 [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Our post hoc analysis comparing the rates of the secondary outcome or major hemorrhage, like that performed in the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT; ClinicalTrials.gov number, NCT00161070)10 showed no differences between the two groups (1572 patients [15.4%] receiving aspirin plus extended-release dipyridamole and 1563 patients [15.4%] receiving clopidogrel; hazard ratio, 1.00; 95% CI, 0.93 to 1.07).
Subgroup Analyses
The relative difference with regard to the primary outcome of first recurrence of stroke between the group receiving aspirin plus extended-release dipyridamole and the clopidogrel group was consistent across multiple prespecified and exploratory subgroups based on baseline characteristics (Figure 3Figure 3
Hazard Ratios for the Primary Outcome of First Recurrence of Stroke, According to Prespecified and Post Hoc Baseline Characteristics.).Safety Outcomes
Major hemorrhagic events occurred more frequently among recipients of aspirin plus extended-release dipyridamole (419 patients [4.1%]) than among recipients of clopidogrel (365 patients [3.6%]; hazard ratio, 1.15; 95% CI, 1.00 to 1.32). Intracranial hemorrhage (including the 128 hemorrhagic strokes counted in the primary outcome) were significantly more frequent in patients receiving aspirin plus extended-release dipyridamole (147 patients [1.4%], vs. 103 patients receiving clopidogrel [1.0%]; hazard ratio, 1.42; 95% CI, 1.11 to 1.83). There were no significant differences between the two groups in the frequency of death, any hemorrhagic event (major or minor), or thrombotic thrombocytopenic purpura or neutropenia (Table 2). The most commonly reported serious adverse events (in at least 0.4% of patients) are reported in the Supplementary Appendix.
Adverse events leading to permanent discontinuation of the study medication were increased in the group receiving aspirin plus extended-release dipyridamole (1650 patients [16.4%]) as compared with the group receiving clopidogrel (1069 patients [10.6%]). Discontinuations due to adverse events occurred earlier with aspirin plus extended-release dipyridamole, with 49.6% of all such discontinuations occurring within the first 2 months as compared with 32.5% of those in the clopidogrel group. Permanent discontinuation of study medication due to headache was more frequent among recipients of aspirin plus extended-release dipyridamole (593 [5.9%]) than among recipients of clopidogrel (87 [0.9%]). Headache also occurred more frequently in the group receiving aspirin and extended-release dipyridamole (30.2% of patients by day 7, vs. 10.2% in the group receiving clopidogrel). Incidence rates for selected adverse events leading to discontinuation are listed in Table 3Table 3
Incidence of Selected Adverse Events Leading to Permanent Discontinuation of Study Medications. (with all occurring in at least 0.1% of patients reported in the Supplementary Appendix).Discussion
The PRoFESS trial provides important evidence regarding the direct comparison of two antiplatelet agents after noncardioembolic stroke. All antiplatelet agents tested in this trial were already approved for the prevention of recurrent stroke in most of the participating countries. The trial did not meet the predefined statistical criteria for noninferiority, but it showed similar rates of recurrent stroke in the group receiving aspirin and extended-release dipyridamole and in the group receiving clopidogrel. Therefore, the study does not show that either aspirin plus extended-release dipyridamole or clopidogrel is superior to the other in the prevention of recurrent stroke.
There were more hemorrhagic strokes with aspirin plus extended-release dipyridamole than with clopidogrel. However, there was no significant difference in the risk of fatal or disabling stroke. Although indirect evidence from previous randomized trials with aspirin as a comparison drug had suggested that aspirin plus extended-release dipyridamole was more effective than clopidogrel for the prevention of stroke recurrence, direct comparisons within a randomized trial are the most valid estimates of comparative treatment efficacy. The trial results emphasize the need for direct comparisons between active antiplatelet agents in the context of prevention of recurrent stroke. Indirect comparisons are limited by differences in antiplatelet trial designs, populations of patients, choice of drugs to compare with aspirin, and definitions of the primary outcomes.24
Despite similar rates of recurrent stroke in our two treatment groups, we were not able to make a claim of noninferiority. The trial was designed to demonstrate the superiority of aspirin plus extended-release dipyridamole, assuming a 13% relative risk reduction with 82% power. Given the uncertainty about indirect comparisons, we added a noninferiority test with a conservative delta value as a precursor to the superiority test. Power calculations showed that the trial would have a statistical power of 82% to show noninferiority if the relative risk reduction for aspirin plus extended-release dipyridamole as compared with clopidogrel was only 6.5%. Given equivalent efficacies of the two treatments, the trial was substantially underpowered (with only 30% power) to show noninferiority. Furthermore, we chose a very conservative noninferiority margin of 7.5%. Although some statistical guidelines for the derivation of a noninferiority margin have been published,25-27 the choice of margin is still controversial.28,29 If noninferiority is declared, then the clinician may conclude that one treatment is as good as or better than the other. If noninferiority is not found, the clinician cannot be confident, within the specified noninferiority margin, that the treatment of interest is at least as good as the other. Nor can the clinician conclude that the comparison treatment is noninferior to or better than the treatment of interest.
The rates of the composite outcome of stroke, myocardial infarction, or death from vascular causes were identical in the two treatment groups, with narrow confidence intervals, suggesting that there is little likelihood for a clinically important difference between the two regimens with regard to these events. The rates of primary and secondary outcomes were consistent across multiple baseline risk factors. Our trial adds to the evidence that recurrent stroke is the most frequent vascular event among survivors of stroke. Randomized trials involving aspirin added to clopidogrel as compared with aspirin alone have suggested stronger effects of the combination for reducing the composite end point of stroke, myocardial infarction, or death from vascular causes — particularly among patients with acute coronary syndromes15 — and some have questioned the efficacy of aspirin plus extended-release dipyridamole in the prevention of myocardial infarction. Our trial results show that therapy with aspirin plus extended-release dipyridamole and therapy with clopidogrel have similar effects on reduction of the composite of vascular events after stroke, including myocardial infarction.
The trial showed no significant difference in the tertiary outcome of first recurrence of stroke or major hemorrhagic event, but there was an increased risk of intracranial bleeding (including intracerebral hemorrhages, 128 of which were also counted toward the primary outcome of recurrent stroke) among patients treated with aspirin plus extended-release dipyridamole, as compared with patients treated with clopidogrel. Trials of clopidogrel plus aspirin have shown greater risks of life-threatening bleeding as compared with monotherapy.8,16 In both the European Stroke Prevention Study 2 (ESPS2) and ESPRIT, there was no significant increase in the risk of major hemorrhage in the aspirin-plus-dipyridamole group as compared with the aspirin group.5,10,11
The rates of permanent discontinuation of study treatment due to headache were much lower in this study than in previous trials, probably owing to counseling of patients and the option to adjust the dose over a period of days if necessary. Despite this finding, there was a difference in the rates of discontinuation, with more recipients of aspirin plus extended-release dipyridamole than recipients of clopidogrel stopping early.
A significant reduction in the risk of new or worsening congestive heart failure was found with aspirin plus extended-release dipyridamole as compared with clopidogrel. The explanation for this finding is not known, but it may relate to an increase in adenosine level and augmentation of coronary collateralization.30
The PRoFESS trial showed that, among patients with a noncardioembolic ischemic stroke, the risks of recurrent stroke or the composite of stroke, myocardial infarction, or death from vascular causes are similar with aspirin plus extended-release dipyridamole and with clopidogrel. Despite the increased risk of hemorrhagic strokes with aspirin plus extended-release dipyridamole as compared with clopidogrel, the net benefit with regard to the risk of recurrent stroke or major hemorrhagic event was similar in the two groups. Furthermore, there was no significant difference between the two treatments in the risk of fatal or disabling strokes. The large number and international representation of patients, who were from 35 countries or regions, enhances the generalizability of our findings. These findings provide additional safety and efficacy data physicians need in making individual treatment decisions for prevention of recurrent stroke or the combined end point of stroke, myocardial infarction, or death from vascular causes in their patients with stroke.
Supported by Boehringer Ingelheim (which manufactures Aggrenox, a combination of extended-release dipyridamole [200 mg] and aspirin [25 mg], and Micardis [telmisartan, 80 mg]). In selected countries, the telmisartan comparison of the PRoFESS study was supported by Bayer Schering Pharma and GlaxoSmithKline.
Dr. Sacco reports receiving consulting fees from Boehringer Ingelheim, GlaxoSmithKline, and Sanofi-Aventis and lecture fees from Boehringer Ingelheim; Dr. Diener, honoraria and consulting and lecture fees from Abbott, AstraZeneca, Bayer Vital, Bristol-Myers Squibb, Boehringer Ingelheim, D-Pharm, Fresenius, GlaxoSmithKline, Janssen Cilag, Merck Sharp & Dohme, Novartis, Novo Nordisk, Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Sankyo, Servier, Solvay, Thrombogenics, Wyeth, and Yamaguchi and grant support from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Janssen-Cilag, and Sanofi-Aventis; and Dr. Yusuf, consulting and lecture fees from Boehringer Ingelheim, Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, and GlaxoSmithKline and grant support from Sanofi-Aventis, Bristol-Myers Squibb, and GlaxoSmithKline. Mr. Cotton, Dr. Ôunpuu, Mr. Lawton, Dr. Gu, Dr. Hermansson, Dr. Hilbrich, Dr. Machnig, Dr. VanderMaelen, and Dr. Voigt report being employees of Boehringer Ingelheim. Drs. Palesch, Martin, Bath, Chen, De Keyser, and Estol report receiving consulting fees from Boehringer Ingelheim; Dr. Albers, consulting and lecture fees from Boehringer Ingelheim and grant support from Boehringer Ingelheim, NMT Medical, Parexel International, AstraZeneca, and Forest Research Institute; Dr. Dahlöf, consulting fees from Boehringer Ingelheim, Daiichi-Sankyo, and Novartis and lecture fees from Boehringer Ingelheim, Novartis, and Pfizer; Dr. Donnan, Mr. Roberts, and Dr. Kaste, consulting and lecture fees from Boehringer Ingelheim; Dr. Gorelick, consulting fees from Boehringer Ingelheim, Bayer, TAP Pharmaceutical Products, Myriad, Pfizer, Takeda, Daiichi Sankyo, Novartis, Merck, Brainsgate, and D-Pharm and lecture fees from Boehringer Ingelheim and diaDexus; Dr. Pais, consulting fees and grant support from Boehringer Ingelheim; Dr. Teal, consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, Boehringer Ingelheim, and Bayer and lecture fees from Sanofi-Aventis, Bristol-Myers Squibb, and Boehringer Ingelheim; Dr. Toni, consulting fees from Boehringer Ingelheim and lecture fees from Boehringer Ingelheim, Sanofi-Aventis, and Novo Nordisk; and Dr. Weber, consulting fees and speakers' fees or honoraria from Novartis, Bristol-Myers Squibb, Daiichi-Sankyo, Boehringer Ingelheim, GlaxoSmithKline, and Forest Laboratories, consulting fees from Gilead and Takeda, and speakers' fees or honoraria from Sanofi-Aventis. No other potential conflict of interest relevant to this article was reported.
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.
We thank Vicky Hinstridge for technical assistance and Karuna Bellamkonda and Michael Pannucci for programming support.
Source Information
The authors' affiliations are listed in the Appendix.
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@med.miami.edu.
Investigators in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) Study Group are listed in the Appendix.
Appendix
The authors' affliations are as follows: the Miller School of Medicine, University of Miami, Miami (R.L.S.); University of Duisberg-Essen, Essen (H.-C.D.); and Boehringer Ingelheim, Ingelheim (T.M.) — both in Germany; McMaster University & Hamilton Health Sciences (S.Y.) and McMaster University (R.R.), Hamilton, ON; Boehringer Ingelheim, Burlington, ON (S.Ô.); and University of British Columbia, Vancouver (P.T.) — all in Canada; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (D.C., L.H., C.V., T.V.); Boehringer Ingelheim, Bracknell (W.A.L.); and University of Nottingham, Nottingham (P.B.) — both in the United Kingdom; Medical University of South Carolina, Charleston (Y.P., R.H.M.); Stanford University Medical Center, Palo Alto, CA (G.W.A.); Ichilov Medical Center, Tel Aviv, Israel (N.B.); National University Hospital, Singapore, Singapore (B.P.L.C.); Chang Gung Memorial Hospital, Tapei, Taiwan (S.-T.C.); Hospitais da Universidade de Coimbra, Coimbra, Portugal (L.C.); Sahlgrenska University Hospital–Östra, Göteborg, Sweden (B.D.); University Medical Center Groningen, Groningen, the Netherlands (J.D.K.); University of Melbourne, Heidelberg West, Australia (G.A.D.); Neurological Center for Treatment and Research, Buenos Aires (C.E.); University of Illinois, Chicago (P.G.); Boehringer Ingelheim Shanghai Pharmaceuticals (V.G.) and Huashan Hospital (C.L.) — both in Shanghai, China; Boehringer Ingelheim, Stockholm (K.H.); Helsinki University Central Hospital, Helsinki (M.K.); St. Johns's Medical College, Bangalore, India (P.P.); Russian State Medical University, Moscow (V.S.); University La Sapienza, Rome (D.T.); SUNY Downstate College of Medicine, New York (M.W.); and Seoul National University Hospital, Seoul, Korea (B.-W.Y.).
The PRoFESS study investigators are as follows: Trial Management and Steering Committee: Current voting members — H.-C. Diener, R. Sacco, S. Yusuf (cochairs); Current nonvoting sponsor members — D. Cotton, V. Gu, K. Hermansson, W.A. Lawton, S. Ôunpuu, C. VanderMaelen, T. Voigt; Previous nonvoting sponsor members — B. Blank, L. Hilbrich, Y. Wu; Steering Committee: Voting members — G. Albers, P. Bath, N. Bornstein, B. Chan, S.-T. Chen, L. Cunha, B. Dahlöf, J. DeKeyser, G. Donnan, C. Estol, P. Gorelick, M. Kaste, C. Lu, P. Pais, R. Roberts, V. Skvortsova, P. Teal, D. Toni, M. Weber, B.-W. Yoon; Nonvoting sponsor members — T. Machnig, M. Humphreys; Data and Safety Monitoring Committee: P. Wolf (chair), M. Fisher, B. Norrving, Y. Palesch (independent statistician), P. Sleight, A. Turpie; Adjudication Committee: T. Buck, J. Chong, G. Dagenais, R. delaPaz, A. Diehl, M. DiTullio, D. Easton, C. Ehrenfeld, M. Elkind, J. Fiebach, M. Forsting, E. Gizewski, D. Gohs, J. Halperin, M. Haude, C. Herz, S. Homma, O. Kastrup, J. Krakauer, A. Magun, M. Maschke, J.P. Mohr, C. Möller-Hartmann, P. Mummel, J. Pile-Spellman, C. Rodriguez, S. Sack, J. Schlaak, A. Schmermund, R. von Kummer, I. Wanke, C. Weimar, H. Wieneke, T. Zoepf; Publication Committee: H.-C. Diener (chair), P. Bath, G. Donnan, D. Cotton, C. Estol, L. Hilbrich, M. Humphreys (previous members), S. Ôunpuu, R. Roberts, P. Teal, D. Toni, R. Sacco, S. Yusuf; Substudy Committee: P. Bath, R. Sacco (cochairs), D. Cotton, B. Dahlöf, H.-C. Diener, P. Gorelick, R. Roberts, M. Weber, S. Yusuf, L. Hilbrich (previous member); Principal Investigators (according to country): Argentina: C. Estol (national coordinator), S. Ameriso, D. Baumann, J.J. Cirio, T.S. Coleman, M.M. Esnaola y-Rojas, H. Fraiman, H. Gabrielli, J. Garrote, M. Garrote, P. Loli, J.L. Ferreiro, S. Lepera, M.F. Pardal, R. Rey, A. Ruiz, G. Saredo, C. Simonsini, A. Zinnerman; Australia: G. Donnan (national coordinator), C. Bladin, D. Crimmins, S. Davis, J. Frayne, P. Hand, R. Henderson, N. Ingham, C. Levi, M. Parsons, S. Read, D. Schultz, A. Slattery, M. Williams, J.A. Zavala; Austria: S. Horner (national coordinator), F. Aichner, M. Brainin, U. Baumhackl, T. Brücke, W. Doppler, V. Dorda, H.-P. Haring, A. Seiser, H.W. Wege, G. Wille, J. Willeit; Belgium: S. Blecic (previous member), V. Thijs (national coordinators), B. Bruneel, J. Caekebeke, N. De Klippel, A. De Windt, P.P. De Deyn, P. Desfontaines, S. Dethy, M. Dupuis, A. Görner, S. Jeangette, P. Laloux, M. Pandolfo, A. Peeters, R. Sheorajpanday, W. Van Landegem, P. Vermylen, G. Vanhooren, C. Willems; Brazil: A.R. Massaro (national coordinator), C. André, A.C.F. Almeida, R. Brondani, J.J. Carvalho, F. Cendes, G.R. de Freitas, S.R.F. Fábio, M.A.G. Friedrich, M. Martins, S.C.O. Martins, A.B. Maulaz, C. Minelli, C.H.C. Moro, J. Oliveira-Filho, M.S. Rocha, J.I. Siqueira-Neto, R. Valiente, V.H.F. Zétola; Canada: P. Teal (national coordinator), N. Amir, B.A. Anderson, R. Arts, P. Bailey, N. Bayer, M. Beaudry, L. Berger, J.-M. Boulanger, D. Brunet, T. Collier, R. Côté, V. Daniels, A. Demchuk, H. Desai, A.M. Fontaine, M. Gawel, D. Gladstone, W. Goldstein, V. Hachinski, F. Herbert, K. Hesser, H. Hink, K. Ho, D. Howse, K. Kastelic, P. Kostyrko, M. Lapierre, L.-H. Lebrun, A. Mackey, M. Maharaj, L. Miners, J. Minuk, G. Moddel, R. Mosewich, D. Novak, A. Penn, Y. Pesant, P. Pikl, A. Rabinovitch, H. Rabinovitch, D. Sahlas, C. Schanz, J. Scott, D. Selchen, M. Sharma, A. Shuaib, J. Silva, F.L. Silver, D. Spence, M. Stefanelli, S. Stoger, T. Stokes, J. Teitelbaum, F. Veloso, S. Verreault, C. Voll, C. Walker, S. Walker, R. Wiegner, T. Winder, M. Winger, A. Woolfenden; China: C. Lu (national coordinator), D.W. Chen, H.B. Chen, S.D. Chen, Y. Cheng, Z.F. Chi, L.Y. Cui, Q. Di, F. Deng, M.P. Ding, S.J. Ding, X.S. Ding, D.S. Fan, W. Fan, X.B. Fan, H.L. Feng, J. Gong, T. Gong, Z. Hong, X.J. Hou, X.Q. Hu, Y.N. Huang, C.Y. Li, L. Li, T. Li, W. Li, Z.Y. Li, H. Lin, Q.Y. Lin, C.F. Liu, J.R. Liu, J.R. Liu, M. Liu, R. Liu, X.F. Liu, Y. Liu, G.G. Luo, G.Q. Luo, J.T. Miao, L. Miao, Z.Y. Pang, W. Qiu, B. Shao, X.J. Sun,, D.X. Wang, F. Wang, L.J. Wang, S.Z. Wang, W. Wang, Y.J. Wang, J. Wu, J. Xia, E. Xu, H.Q. Xu, S.B. Xu, X. Xu, Q.D. Yang, X. Yi, P.M. Yu, G.L. Zeng, J.S. Zeng, Y. Zhai, B. Zhang, C.Y. Zhang, H. Zhang, S.H. Zhang, W.W. Zhang, Y.B. Zhang, Y. Zhang, Y. Zhang, G. Zhao, J.H. Zhao, J. Zhao, X.Q. Zhao, G.X. Zhou, H.D. Zhou, G.M. Zhu, Y.C. Zhu; Denmark: P. Petersen (national coordinator), G. Andersen, P. Arlien-Soeborg, I.C. Bach, M. Binzer, G. Boysen, A. Heick, A.-M. Homburg, S. Husted, H. Iversen, L.-H. Krarup, T.S. Olsen, K. Overgaard, P. Von Weitzel-Mudersbach; Finland: M. Kaste (national coordinator), M. Hillbom, K. Koivisto, M. Männikkö, S. Mustanoja, H. Numminen, J. Nuutinen, J. Sivenius; France: X. Ducrocq (national coordinator), D. Leys, C. Lucas, F. Macian, L. Milandre, J.-P. Neau, D. Saudeau, H. Vespignani, M. Voicu, M. Zuber; Germany: O. Busse (national coordinator), A. Ahlers, J. Allendoerfer, R. Benecke, S. Boy, A. Dethlefs, M. Dichgans, H.-C. Diener, M. Eicke, F. Erbguth, G. Gahn, S. Gass, J. Glahn, M. Görtler, A. Grau, B. Griewing, M. Grond, K.-H. Grotemeyer, J. Haan, G. Hamann, L. Harms, S. Harscher, A. Hetzel, A. Hoferichter, H.B. Huelsboemer, G. Ickenstein, M. Kaps, M. Kirchner, H. Kunte, J. Liepert, R. Malessa, Y. Mewald, A. Müller-Jensen, D. Nabavi, M. Nedelmann, M. Nueckel, H. Poppert, K. Rabe, J. Regula, P. Ringleb, M. Rosenkranz, W.-R. Schaebitz, I. Schaberger, F. Schlachetzki, D. Schneider, J. Schrader, U. Sliwka, J. Sobesky, H. Soda, W. Steinke, H.G. Thomalla, H. Topka, J. Treib, M. Vry, T. Warnecke, R. Weber, C. Weiller, K. Wessel, H. Wiethölter, O. Witte, H. Wuttig; Greece: I. Iliopoulos (national coordinator), I. Ellul, S. Giannopoulos, C. Karageorgiou, P. Papathanasopoulos, D. Vassilopoulos, S. Voyaki; Hong Kong: P.W. Ng (national coordinator), B.H. Fung, K.F. Hui, T. Leung, V. Mok, K.S. Wong; India: D. Xavier (national coordinator), A. Agarwal, R.R. Agrawal, A.M. Anandan, V. Anandhi, G.K. Babu, S. Bandishti, A. Bhargava, N. Bhargava, A. Bharani, A. Bhatt, N. Chidambaram, Y. Dewan, M. Dinaker, R. Joshi, S. Joshi, A. Kalanidhi, S.P. Kalantri, S. Kothari, A. Kumar, P. Kumar, V. Jain, M.M. Mehndiratta, S. Mijar, V. Mishra, S. Murali, R.S. Muralidharan, J.M.K. Murthy, R. Nair, J.T. Narayanan, R.B. Panwar, P. Patel, F. Poncha, V.V.R. Prasad, A. Rath, B.C.S. Reddy, A. Rohatgi, A.K. Roy, S. Sadanandham, A. Salam, G.R.K. Sarma, H. Singh, Y. Singh, S. Shanmugasundaram, S. Sharma, S. Sivakumar, R. Sundararajan, T. Sundararajan, U. Tukaram, R. Umarani, S. Varma, C.U. Velmurugendran, A. Venkitachalam, R. Verghese, K.P. Vinayan, A. Vyas, R.S. Wadia; Ireland: R. Galvin (national coordinator), P. Kelly, D. O'Mahony; Israel: N. Bornstein (national coordinator), B. Assa-Meirov, B. Gross, Y. Lampl, A. Mahagney, O. Merzlyak, R. Milo, M. Rabey, L. Shopin, J. Streifler, D. Tanne, G. Telman, L. Turiansky, B. Weller, D. Yarnitsky; Italy: L. Provinciali (national coordinator), M. Arnaboldi, P. Bassi, B. Bergamasco, A. Carolei, G. Cascone, F. Chiodo Grandi, G. Comi, D. Consoli, F. Corea, P. Dudine, F.A. De Falco, C. Gandolfo, E. Giaccaglini, B. Gobbi, D. Inzitari, G. Lembo, M. Melis, R. Mutani, E. Natalé, G. Neri, M. Rasura, M.L. Sacchetti, A. Semplicini, M. Stornello, M. Stramba-Badiale, R. Sterzi, G. Torcasio, V. Toso; Japan: S. Uchiyama, T. Yamaguchi (national coordinators), K. Chiba, Y. Fujino, F. Hattori, K. Hattori, O. Hirai, A. Imamura, K. Ishii, T. Ishihara, M. Isobe, K. Ito, T. Jinnouchi, M. Kaido, T. Kawamoto, M. Kawanishi, I. Kim, K. Kitazawa, M. Kotera, Y. Kujiraoka, S. Kurokawa, Y. Maeda, K. Matsumoto, M. Matsumoto, S. Matsumoto, F. Nakagawa, Y. Nakajima, T. Obata, H. Ohnishi, N. Sato, T. Seguchi, T. Seki, Y. Shibagaki, M. Shitamichi, A. Tabuchi, K. Takahashi, M. Takekawa, Y. Takimoto, H. Tanabe, H. Taniguchi, Y. Tatsuoka, K. Toda, T. Toriyama, M. Yamazaki, H. Yoshida; Malaysia: K.S. Tan (national coordinator), T. Hassan, H.T. Chong, K.S. Tan, J.K.J. Tharakan; Mexico: A. Arauz (national coordinator), J. Aguayo, C. Cantu, C. Espinoza, J. Fernández-Vera, J. Guzman, C. León, A. Leyva, M. López, M. López-Ruiz, S. Reyes, J. Ruiz, R. Vazquez, J. Villarreal; the Netherlands: J. De Keyser (national coordinator), M. Aramideh, J. Boiten, P. Brouwers, B. de Bruijn, C. Franke, J. den Heijer, P. Dellemijn, J. Hagemans, K. Keizer, S. Kok, P. de Kort, J. de Kruijk, J. Kuipers-Lo Dico, J. van Leusden, H. van Leusen, B. Jansen, W.M. Mulleners, K. ten Napel, J.F. de Rijk-van Andel, J. Van Remmen, W. Rutgers, W.J. Schonewille, T. Simons, T.J. Tacke, E. Vries, J. Wessel, M. van Zagten; Norway: B. Indredavik (national coordinator), H. Næss, G. Rohweder, Ø. Røsjø; Portugal: L. Cunha (national coordinator), J. Campillo, J.M. Ferro, G. Lopes, A.A. Pinto, V. Salgado; Russia: V. Skvortsova (national coordinator), V. Alifirova, A. Amintaeva, O. Antukhova, G. Avakyan, A. Belkin, A. Belova, A. Boiko, A. Boiko, V. Bulgakov, M. Cherman, N. Dokuchaeva, B. Doronin, M. Evzelman, A. Fedin, N. Fedorova, O. Gileva, M. Glezer, K. Golikov, N. Halo, E. Isakova, A. Ivleva, L. Kabanova, S. Kotov, A. Kovalenko, G. Kozin, T. Lokshtanova, M. Lutsky, R. Magzhanov, M. Martynov, T. Mirsaev, D. Mulyarov, V. Narodova, M. Odinak, A. Orlov, V. Parfenov, N. Pizova, J. Popova, E. Poroshina, S. Pronina, N. Pryanikova, E. Pynchuk, L. Renzhina, A. Savchenko, E. Shirokov, V. Shmyrev, I. Sholomov, N. Shmidt, V. Simanenkov, A. Skoromets V. Sorokoumov, N. Spirin, L. Stakhovskaya, A. Stepanchenko, E. Strachunskaya, V. Stulin, Z. Suslina, S. Timerbaeva, Y. Trinitatsky, Y. Varakin, O. Voskresenskaya, E. Yacupov, N. Yahno, S. Yanishevsky, G. Yudina, Y. Yudelson, J. Zhitkova; Singapore: B.P.L. Chan (national coordinator), H.M. Chang, C.C. Chen, W. Cheong, D.A. De Silva, R.N. Gan, C. Meng, A.B.H. Seah, V.K. Sharma, C.S.P. Soon, N. Venketasubramanian, Y. Wai, M.C. Wong, C.W. Yip; South Africa: J. Smuts (national coordinator), P. Francis, J. Gardiner, W. Guldenpfennig, D. Lurie, A. Mochan, C. Retief, W. Van Niekerk; South Korea: B.-W. Yoon (national coordinator), O.-Y. Bang, K.-H. Cho, S.-W. Han, J.-H. Heo, D.-W. Kang, H.-A. Kim, H.-M. Kwon, J.-H. Kwon, S.-U. Kwon, B.-C. Lee, H.-S. Nam, M.-S. Park, J.-H. Rha, K.-H. Yu; Spain: A. Gil-Nunez (national coordinator), J. Alvarez-Sabín, C. Antón, J.A. Egido, J. Gállego, F. Gracia, J.M. Moltó, R. Navarro, F. Rubio. Sweden: N.-G. Wahlgren (national coordinator), B. Andersson, M. von Arbin, A. Berglund, E. Bertholds, L. Bokemark, C. Carlstroem, A.-C. Elgåsen, J.P. Eriksson, P.-O. Hansson, T.-B. Käll, A. Lindgren, J. Lökk, J. Malm, I. Markström, M. Milovanovic, S.-Å. Nilsson, B. Persson, Ö. Skogar, M. Stenstam, J. Teichert, S. Karlsson-Tivenius, M. Von Euler, T. Wallén; Taiwan: S.-T. Chen (national coordinator), K.-C. Chang, M.-H. Chang, Y.-J. Chang, C.-H. Chen, W.-H. Chen, Y.-T. Chuang, C.-Y. Hsu, H.-H. Hu, Y.-C. Huang W.-J. Hwang, J.-S. Jeng, J.-T. Lee, L.-M. Lien, R.-T. Lin, Y.-J. Lin, C.-H. Liu, G.-S. Peng, H.L. Po, T.-Y. Tan, S.-C. Tsai, S.-F. Wang, W.-J. Wong; Thailand: S. Chankrachang, Y. Chinvarun, A. Chutinet, S. Muengtaweepongsa, Y. Nilanont, N. Poungvarin, P. Sithinamsuwan, N. Suwanwela, S. Tanprawate; Turkey: S. Bahar (national coordinator), S. Aktan, M. Bakar, S. Balkan, T. Dalkara, K. Kutluk, G. Ozdemir; Ukraine: S. Moskovko (national coordinator), O. Balyskyy, V. Bitensky, O. Dubenko, L. Dzyak, A. Goloborodko, G. Grebenyuk, A. Koselkin, V. Kulgeyko, S. Kuznetzova, V. Lebedynets, V. Maly, S. Medvedkova, E. Melnyk, T. Mishchenko, G. Moskovko, V. Orzheshkovskyy, N. Ovsyannikova, V. Yavorska, I. Yurdanova, V. Zushkha; United Kingdom: P. Bath (national coordinator), L. Brawn, M. Brown, L. Campbell, D. Cohen, R. Curless, J. Davis, G. Durward, G. Ford, C. Gray, F.L. Hammonds, T. Hendra, M. James, L. Kalra, R. Kumar, S. Jackson, D. Jenkinson, K. Lees, G. Lip, R. MacWalter, K. Muir, P. Murphy, J. Okwera, E. Orugun, P. Passmore, J. Potter, A. Sharma, J. Sharma, M. Sterling, S. Ragab, T. Robinson, C. Roffe, A. Rowe, J. Turton; United States: G. Albers (national coordinator), P. Gorelick (national coordinator), R. Sacco (national coordinator), F. Abbott, J. Absher, A. Acharya, H. Adams, P. Akins, E. Albakri, M. Alberts, R. Alonso, I. Altafullah, E. Anderson, J. Andrefsky, R. Armstrong, G. Arnold, A. Arora, R. Atkinson, S. Azhar, S. Bansil, K. Becker, R. Bell, L. Benardo, G. Bernardini, A. Bernstein, P. Blachman, J. Boiser, B. Boop, C. Boutwell, D. Bressler, C. Brooks, W. Brooks, R. Calhoun, F. Campanella, S. Carlson, D. Carpenter, J. Castaldo, R. Castaldo, M. Cauli, K. Chan, S. Chaturvedi, S. Cherian, M. Chesser, D. Chiu, W. Clark, B. Cleeremans, S. Cohen, T. Coin, L. Collins, M. Concha, G. Cooper, J. Couch, B. Coull, E. Crisostomo, A. Cruz, P. Cullis, R. Dafer, S. Dash, D. Davis, P. Davis, J. DeMatteis, B. Diamond, A. Dick, D. Dietrich, R. Dunnigan, D. Duong, L. Edelsohn, H. Ehrenfeld, J. Elkins, M. Englert, S. Erlemeier, G. Eubank, P. Fayad, R. Felberg, W. Felton III, R. Ferguson, S. Flitman, P. Fonzetti, K. Furie, M. Garcia, G. Gardziola, J. Gebel, J. Glass, L. Goldstein, A. Goldszmidt, S. Goli, G. Graham, D. Graybeal, B. Grayum, E. Green, J. Green, P. Green, D. Greer, T. Gropen, J. Gross, J. Grotta, R. Gunwardane, B. Haake, T. Habiger, J. Halsey, D. Hanley, J. Hanna, C. Hansen, S. Hanson, G. Harpold, J. Harris, M. Harris, R. Hart, K. Hedges, B. Hendin, J. Hinchey, J. Ho, M. Hoffman, J. Hollander, W. Holt, K. Holzmacher, G. Howell, S. Howell, D. Huang, R. Hughes, R. Hull, T. Hwang, M. Jacobson, M. Jacoby, A. Jayam-Trouth, C. Jackson, K. John, B. Johnson-Finley, M. Johnson, S. Johnston, A. Kamal, P. Karanjia, C. Kase, S. Kasner, L. Katz, P. Katz, T. Kent, R. Kelley, C. Kidwell, A. Khanna, H. Kirshner, D. Kleindorfer, C. Knox, J. Kramer, L. Labiche, R. Lada, E.F. LaFranchise, M. LaMonte, M. Lee, P. Lee-Kwen, D. Leifer, E. Leira, K. Levin, R. Libman, D. Liebeskind, K. Lindholm, J.N. Livingstone II, G. Locke, W. Logan, J. Luciano, H. Lutsep, A. Majid, V. Mangeshkumar, S. Markind, L. Mate, J. McCain IV, W.A. McElveen, B. McKown, J. Merino, B. Meyer, T. Mikesell, T. Mirsen, L. Montoya, S. Moon, M. Moonis, K. Moore, J. Nasrallah, A. Nassief, M. Nelson, F. Nichols, J. Osborne, F. Oser, B. Ovbiagele, D. Palestrant, S. Panezai, N. Papamitsakis, G. Parry, M. Perez, C. Perkins, J. Porter, W. Preston, H. Rabiee, M. Raikhel, R. Reichwein, K. Remmel, B. Richardson, R. Ringel, D. Rosenbaum, D. Ross, M. Rubin, K. Ruffing, H. Sachdev, M. Sauter, J. Saver, J. Schafer, R. Schiftan, J. Schim, A.K. Schleining, M. Schneck, M. Selim, S. Sen, S. Shafer, B. Shafran, S. Sharfstein, D. Sherman, C. Sila, S. Silliman, B. Silver, B. Silverman, I. Silverman, R. Singh, N. Skillings, A. Slivka, D. Smith, R. Soto, S. Sparr, R. Stephens, H. Sullivan, G. Sung, J. Sutherland, A. Syed, M. Tabbaa, D. Tamulonis, R. Taylor, D. Tesfaye, T. Thomas, G. Tietjen, A. Todorov, M. Torbey, B. Tolge, M. Tremwell, W. Truax, D. Unwin, A. Vaishnav, N. Varma, Y.S. Venkatesh, P. Verro, R. Verson, T. Vidic, P. Vrooman, R. Wallis, D. Wang, J. Wang, M. Waters, L. Wechsler, J. Weinberger, J. Weissman, G. Wheatley, R. Whitehead, A. Willhite, H. Willis, E. Wilson, R. Wilson, J. Wilterdink, E. Wirkowski, M. Wozniak, C. Wright, M. Young, S. Zachariah, S. Zuckerman, R. Zweifler.
- References
References
1
Dhamoon MS ,Sciacca RR ,Rundek T ,Sacco RL ,Elkind MS . Recurrent stroke and cardiac risks after first ischemic stroke: the Northern Manhattan Study. Neurology 2006;66:641-646
CrossRef | Web of Science | Medline2
Gent M ,Blakely JA ,Easton JD , et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989;1:1215-1220
CrossRef | Web of Science | Medline3
Hass WK ,Easton JD ,Adams HP Jr , et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med 1989;321:501-507
Full Text | Web of Science | Medline4
CAPRIE Steering Committee
CrossRef | Web of Science | Medline5
Diener HC ,Cunha L ,Forbes C ,Sivenius J ,Smets P ,Lowenthal A . European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996;143:1-13
CrossRef | Web of Science | Medline6
Mohr JP ,Thompson JLP ,Lazar RM , et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001;345:1444-1451
Full Text | Web of Science | Medline7
Antithrombotic Trialists' Collaboration
CrossRef | Web of Science8
Diener HC ,Bogousslavsky J ,Brass LM , et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004;364:331-337
CrossRef | Web of Science | Medline9
Chimowitz MI ,Lynn MJ ,Howlett-Smith H , et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 2005;352:1305-1316
Full Text | Web of Science | Medline10
The ESPRIT Study Group
CrossRef | Web of Science | Medline11
The ESPRIT Study Group
CrossRef | Web of Science | Medline12
Sacco RL ,Adams R ,Albers G , et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:577-617
CrossRef | Web of Science | Medline13
European Stroke Organization (ESO) Executive Committee, ESO Writing Committee
CrossRef | Web of Science | Medline14
Thijs V ,Lemmens R ,Fieuws S . Network meta-analysis: simultaneous meta-analysis of common antiplatelet regimens after transient ischaemic attack or stroke. Eur Heart J 2008;29:1086-1092
CrossRef | Web of Science | Medline15
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators
Full Text | Web of Science | Medline16
Bhatt DL ,Fox KAA ,Hacke W , et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354:1706-1717
Full Text | Web of Science | Medline17
Hirsh J ,Guyatt G ,Albers GW ,Schunemann HJ . The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: evidence-based guidelines. Chest 2004;126:Suppl:172S-173S
CrossRef | Web of Science | Medline18
Diener HC ,Sacco R ,Yusuf S . Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS). Cerebrovasc Dis 2007;23:368-380
CrossRef | Web of Science | Medline19
Adams HP Jr ,Bendixen BH ,Kappelle LJ , et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial: TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41
CrossRef | Web of Science | Medline20
van Swieten JC ,Koudstaal PJ ,Visser MC ,Schouten HJ ,van Gijn J . Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604-607
CrossRef | Web of Science | Medline21
Mahoney FI ,Barthel DW . Functional evaluation: the Barthel Index. Md State Med J 1965;14:61-65
Medline22
Haybittle JL . Repeated assessment of results in clinical trials of cancer treatment. Br J Radiol 1971;44:793-797
CrossRef | Web of Science | Medline23
Fisher LD ,Gent M ,Buller HR . Active-control trials: how would a new agent compare with placebo? A method illustrated with clopidogrel, aspirin, and placebo. Am Heart J 2001;141:26-32
CrossRef | Web of Science | Medline24
Gorelick PB ,Richardson D ,Kelly M , et al. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. JAMA 2003;289:2947-2957
CrossRef | Web of Science | Medline25
Laster LL ,Johnson MF . Non-inferiority trials: the `at least as good as' criterion. Stat Med 2003;22:187-200
CrossRef | Web of Science | Medline26
Wang S-J ,Hung HMJ . TACT method for non-inferiority testing in active controlled trials. Stat Med 2003;22:227-238
CrossRef | Web of Science | Medline27
Fleming TR . Current issues in non-inferiority trials. Stat Med 2008;27:317-332
CrossRef | Web of Science | Medline28
James Hung HM ,Wang S-J ,Tsong Y ,Lawrence J ,O'Neil RT . Some fundamental issues with non-inferiority testing in active controlled trials. Stat Med 2003;22:213-225
CrossRef | Web of Science | Medline29
D'Agostino RB ,Massaro JM ,Sullivan LM . Non-inferiority trials: design concepts and issues -- the encounters of academic consultants in statistics. Stat Med 2003;22:169-186
CrossRef | Web of Science | Medline30
Akhtar M ,Ordovas K ,Martin A ,Higgins CB ,Michaels AD . Effect of chronic sustained-release dipyridamole on myocardial blood flow and left ventricular function in patients with ischemic cardiomyopathy. Congest Heart Fail 2007;13:130-135
CrossRef | Medline
- Citing Articles (154)
Citing Articles
1
2013. S. , 970-1062.
CrossRef2
Davis, Stephen M., Donnan, Geoffrey A., . (2012) Secondary Prevention after Ischemic Stroke or Transient Ischemic Attack. New England Journal of Medicine 366:20, 1914-1922
Full Text3
, J. Perk, G. De Backer, H. Gohlke, I. Graham, Z. Reiner, M. Verschuren, C. Albus, P. Benlian, G. Boysen, R. Cifkova, C. Deaton, S. Ebrahim, M. Fisher, G. Germano, R. Hobbs, A. Hoes, S. Karadeniz, A. Mezzani, E. Prescott, L. Ryden, M. Scherer, M. Syvanne, W. J. M. Scholte Op Reimer, C. Vrints, D. Wood, J. L. Zamorano, F. Zannad, , M. T. Cooney, , J. Bax, H. Baumgartner, C. Ceconi, V. Dean, C. Deaton, R. Fagard, C. Funck-Brentano, D. Hasdai, A. Hoes, P. Kirchhof, J. Knuuti, P. Kolh, T. McDonagh, C. Moulin, B. A. Popescu, Z. Reiner, U. Sechtem, P. A. Sirnes, M. Tendera, A. Torbicki, A. Vahanian, S. Windecker, , C. Funck-Brentano, P. A. Sirnes, V. Aboyans, E. A. Ezquerra, C. Baigent, C. Brotons, G. Burell, A. Ceriello, J. De Sutter, J. Deckers, S. Del Prato, H.-C. Diener, D. Fitzsimons, Z. Fras, R. Hambrecht, P. Jankowski, U. Keil, M. Kirby, M. L. Larsen, G. Mancia, A. J. Manolis, J. McMurray, A. Pajak, A. Parkhomenko, L. Rallidis, F. Rigo, E. Rocha, L. M. Ruilope, E. van der Velde, D. Vanuzzo, M. Viigimaa, M. Volpe, O. Wiklund, C. Wolpert. (2012) European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts) * Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). European Heart Journal
CrossRef4
Valeria Caso, Paola Santalucia, Monica Acciarresi, Francesca Romana Pezzella, Maurizio Paciaroni. (2012) Antiplatelet treatment in primary and secondary stroke prevention in women. European Journal of Internal Medicine
CrossRef5
Belinda Cruse, Lucette A. Cysique, Romesh Markus, Bruce J. Brew. (2012) Cerebrovascular disease in HIV-infected individuals in the era of highly active antiretroviral therapy. Journal of NeuroVirology
CrossRef6
Morrow, David A., Braunwald, Eugene, Bonaca, Marc P., Ameriso, Sebastian F., Dalby, Anthony J., Fish, Mary Polly, Fox, Keith A.A., Lipka, Leslie J., Liu, Xuan, Nicolau, José Carlos, Ophuis, A.J. Oude, Paolasso, Ernesto, Scirica, Benjamin M., Spinar, Jindrich, Theroux, Pierre, Wiviott, Stephen D., Strony, John, Murphy, Sabina A., . (2012) Vorapaxar in the Secondary Prevention of Atherothrombotic Events. New England Journal of Medicine 366:15, 1404-1413
Full Text7
Matthew S. West, Ethan U. Cumbler. (2012) Acute Ischemic Stroke. Hospital Medicine Clinics 1:2, e223-e237
CrossRef8
Dirk M Hermann, Michael Chopp. (2012) Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. The Lancet Neurology 11:4, 369-380
CrossRef9
John G. F. Cleland, Saqib Mumtaz, Luca Cecchini. (2012) Role of Antithrombotic Agents in Heart Failure. Current Cardiology Reports
CrossRef10
Patrizia Ferroni, Natale Vazzana, Silvia Riondino, Chiara Cuccurullo, Fiorella Guadagni, Giovanni Davi'. (2012) Platelet Function in Health and Disease: from Molecular Mechanisms, Redox Considerations to Novel Therapeutic Opportunities. Antioxidants & Redox Signaling120329080234008
CrossRef11
Bruce A. Warden, Alana M. Willman, Craig D. Williams. (2012) Antithrombotics for secondary prevention of noncardioembolic ischaemic stroke. Nature Reviews Neurology
CrossRef12
Tomomi Nakamura, Shinji Tsuruta, Shinichiro Uchiyama. (2012) Cilostazol combined with aspirin prevents early neurological deterioration in patients with acute ischemic stroke: A pilot study. Journal of the Neurological Sciences 313:1-2, 22-26
CrossRef13
Yong-Jun Wang, Su-Ming Zhang, Liqun Zhang, Chun-Xue Wang. (2012) Chinese Guidelines for the Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack 2010. CNS Neuroscience & Therapeutics 18:2, 93-101
CrossRef14
Almut Grenz, Jessica D. Bauerle, Julee H. Dalton, Douglas Ridyard, Alexander Badulak, Eunyoung Tak, Eóin N. McNamee, Eric Clambey, Radu Moldovan, German Reyes, Jost Klawitter, Kelly Ambler, Kristann Magee, Uwe Christians, Kelley S. Brodsky, Katya Ravid, Doo-Sup Choi, Jiaming Wen, Dmitriy Lukashev, Michael R. Blackburn, Hartmut Osswald, Imogen R. Coe, Bernd Nürnberg, Volker H. Haase, Yang Xia, Michail Sitkovsky, Holger K. Eltzschig. (2012) Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice. Journal of Clinical Investigation
CrossRef15
Robert Janknegt, Lex Ruiters, Hugo ten Cate. (2012) InforMatrix: ADP antagonists in acute coronary syndromes. Expert Opinion on Pharmacotherapy1-29
CrossRef16
Réza Behrouz, Ali R. Malek, Michel T. Torbey. (2012) Small Vessel Cerebrovascular Disease: The Past, Present, and Future. Stroke Research and Treatment 2012, 1-8
CrossRef17
Robert W.V. Flynn, Thomas M. MacDonald, Gordon D. Murray, Ronald S. MacWalter, Alexander S.F. Doney. (2012) Persistence, Adherence and Outcomes with Antiplatelet Regimens following Cerebral Infarction in the Tayside Stroke Cohort. Cerebrovascular Diseases 33:2, 190-197
CrossRef18
Masako YAMAZAKI, Shinichiro UCHIYAMA. (2012) Antithrombotic and thrombolytic therapy for ischemic stroke. Japanese Journal of Thrombosis and Hemostasis 23:1, 16-24
CrossRef19
Matthew S. West, Ethan U. Cumbler. (2012) Acute Ischemic Stroke. Hospital Medicine Clinics
CrossRef20
Bruce A. Warden, Alana M. Willman, Craig D. Williams. (2012) Antithrombotics for secondary prevention of noncardioembolic ischaemic stroke. Nature Reviews Neurology
CrossRef21
Larry B. Goldstein. 2012. Prevention and Management of Stroke. , 1359-1367.
CrossRef22
2012. Carotid Artery Disease and Extracranial Cerebrovascular Disease. , 19-68.
CrossRef23
Janice B. Schwartz, Douglas P. Zipes. 2012. Cardiovascular Disease in the Elderly. , 1727-1756.
CrossRef24
2012. The Nervous System. , 599-677.
CrossRef25
Arijana Lovrencic-Huzjan, Tatjana Rundek, Michael Katsnelson. (2012) Recommendations for Management of Patients with Carotid Stenosis. Stroke Research and Treatment 2012, 1-12
CrossRef26
Kirtiman Srivastava, Philip M. W. Bath, Ulvi Bayraktutan. (2011) Current Therapeutic Strategies to Mitigate the eNOS Dysfunction in Ischaemic Stroke. Cellular and Molecular Neurobiology
CrossRef27
Maria Czarina Acelajado, Suzanne Oparil. (2011) Antiplatelet Therapy for Transient Ischemic Attack. The Journal of Clinical Hypertensionno-no
CrossRef28
A. D. Michelson. (2011) Advances in Antiplatelet Therapy. Hematology 2011:1, 62-69
CrossRef29
Sidney C. Smith, Emelia J. Benjamin, Robert O. Bonow, Lynne T. Braun, Mark A. Creager, Barry A. Franklin, Raymond J. Gibbons, Scott M. Grundy, Loren F. Hiratzka, Daniel W. Jones, Donald M. Lloyd-Jones, Margo Minissian, Lori Mosca, Eric D. Peterson, Ralph L. Sacco, John Spertus, James H. Stein, Kathryn A. Taubert. (2011) AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update. Journal of the American College of Cardiology 58:23, 2432-2446
CrossRef30
Almut Grenz, Dirk Homann, Holger K. Eltzschig. (2011) Extracellular Adenosine: A Safety Signal That Dampens Hypoxia-Induced Inflammation During Ischemia. Antioxidants & Redox Signaling 15:8, 2221-2234
CrossRef31
Hsuan-Wei Li, Ming-Chin Yang, Kuo-Piao Chung. (2011) Predictors for readmission of acute ischemic stroke in Taiwan. Journal of the Formosan Medical Association 110:10, 627-633
CrossRef32
Paolo Gresele, Stefania Momi, Emanuela Falcinelli. (2011) Anti-platelet therapy: phosphodiesterase inhibitors. British Journal of Clinical Pharmacology 72:4, 634-646
CrossRef33
Stephen D. Wiviott, Nihar Desai, Sabina A. Murphy, Guiseppe Musumeci, Michael Ragosta, Elliott M. Antman, Eugene Braunwald. (2011) Efficacy and Safety of Intensive Antiplatelet Therapy With Prasugrel from TRITON-TIMI 38 in a Core Clinical Cohort Defined by Worldwide Regulatory Agencies. The American Journal of Cardiology 108:7, 905-911
CrossRef34
Helmi Lutsep. (2011) Update on selecting and adjusting antiplatelet therapy for prevention of noncardiogenic, recurrent ischemic stroke. Expert Review of Cardiovascular Therapy 9:10, 1295-1303
CrossRef35
Paul Stoll, Annett Plessow, Kai Bratke, J. Christian Virchow, Marek Lommatzsch. (2011) Differential effect of clopidogrel and aspirin on the release of BDNF from platelets. Journal of Neuroimmunology 238:1-2, 104-106
CrossRef36
B. Fuentes, J. Gállego, A. Gil-Nuñez, A. Morales, F. Purroy, J. Roquer, T. Segura, J. Tejada, A. Lago, E. Díez-Tejedor, M. Alonso de Leciñana, J. Álvarez-Sabin, J. Arenillas, S. Calleja, I. Casado, M. Castellanos, J. Castillo, A. Dávalos, F. Díaz-Otero, J.A. Egido, J.C. López-Fernández, M. Freijo, A. García Pastor, F. Gilo, P. Irimia, J. Maestre, J. Masjuan, J. Martí-Fábregas, P. Martínez-Sánchez, E. Martínez-Vila, C. Molina, F. Nombela, M. Ribó, M. Rodríguez-Yañez, F. Rubio, J. Serena, P. Simal, J. Vivancos. (2011) Guía para el tratamiento preventivo del ictus isquémico y AIT (II). Recomendaciones según subtipo etiológico. Neurología
CrossRef37
P Atwal, S Goheer, G McKay, M Fisher. (2011) Dipyridamole. Practical Diabetes 28:7, 316-317a
CrossRef38
Fadi B. Nahab, Sakib Qureshi. 2011. Antithrombotics for Ischemic Stroke. , 205-222.
CrossRef39
Michael Kornfeld, Joseph R. Munsayac. 2011. Antiplatelet Medications. , 47-65.
CrossRef40
Suzanne V. Arnold, David J. Cohen, Elizabeth A. Magnuson. (2011) Cost-effectiveness of oral antiplatelet agents—current and future perspectives. Nature Reviews Cardiology 8:10, 580-591
CrossRef41
J. Donald Easton. (2011) Antithrombotic Management for Transient Ischemic Attack and Ischemic Stroke (Other than Atrial Fibrillation). Current Atherosclerosis Reports 13:4, 314-320
CrossRef42
Haralampos J. Milionis, Grigorios Gerotziafas, Michael S. Kostapanos, Anastasia Vemmou, Panagiotis Zis, Konstantinos Spengos, Moses Elisaf, Konstantinos N. Vemmos. (2011) Clopidogrel vs. Aspirin Treatment on Admission Improves 5-Year Survival After a First-ever Acute Ischemic Stroke. Data from the Athens Stroke Outcome Project. Archives of Medical Research 42:6, 443-450
CrossRef43
Omair Yousuf, Deepak L. Bhatt. (2011) The evolution of antiplatelet therapy in cardiovascular disease. Nature Reviews Cardiology 8:10, 547-559
CrossRef44
PH. G. STEG, S. H. DORMAN, P. AMARENCO. (2011) Atherothrombosis and the role of antiplatelet therapy. Journal of Thrombosis and Haemostasis 9, 325-332
CrossRef45
Samuel Yip, Oscar Benavente. (2011) Antiplatelet Agents for Stroke Prevention. Neurotherapeutics 8:3, 475-487
CrossRef46
Deborah Bergman. (2011) Preventing recurrent cerebrovascular events in patients with stroke or transient ischemic attack: The current data. Journal of the American Academy of Nurse Practitionersno-no
CrossRef47
Ahmed Alhusban, Susan C. Fagan. (2011) Secondary Prevention of Stroke in the Elderly: A Review of the Evidence. The American Journal of Geriatric Pharmacotherapy 9:3, 143-152
CrossRef48
Robert Guthrie. (2011) Review and management of side effects associated with antiplatelet therapy for prevention of recurrent cerebrovascular events. Advances in Therapy 28:6, 473-482
CrossRef49
Sunil Manjila, Tony Masri, Tanzila Shams, Shakeel A. Chowdhry, Cathy Sila, Warren R. Selman. (2011) Evidence-based review of primary and secondary ischemic stroke prevention in adults: a neurosurgical perspective. Neurosurgical FOCUS 30:6, E1
CrossRef50
Virginia A. Pujol Lereis, Sebastian Ameriso, Guillermo P. Povedano, Sebastián F. Ameriso. (2011) Ischemic Stroke in Patients Receiving Aspirin. Journal of Stroke and Cerebrovascular Diseases
CrossRef51
Jaime Gállego Culleré, María Elena Erro Aguirre. (2011) Basilar Branch Occlusion. Current Treatment Options in Cardiovascular Medicine 13:3, 247-260
CrossRef52
Marie-Germaine Bousser, Pierre Amarenco, Angel Chamorro, Marc Fisher, Ian Ford, Kim M Fox, Michael G Hennerici, Heinrich P Mattle, Peter M Rothwell, Agnès de Cordoüe, Marie-Dominique Fratacci. (2011) Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. The Lancet 377:9782, 2013-2022
CrossRef53
Peter M Rothwell, Ale Algra, Pierre Amarenco. (2011) Medical treatment in acute and long-term secondary prevention after transient ischaemic attack and ischaemic stroke. The Lancet 377:9778, 1681-1692
CrossRef54
Young-Jung Lee, Yoot Mo Lee, Chong-Kil Lee, Jae Kyung Jung, Sang Bae Han, Jin Tae Hong. (2011) Therapeutic applications of compounds in the Magnolia family. Pharmacology & Therapeutics 130:2, 157-176
CrossRef55
H. C. Diener, R. Weber, C. Weimar, J. Röther. (2011) Secondary prevention in the acute and early chronic phase after ischaemic stroke and transient ischaemic attacks with antiplatelet drugs - is antiplatelet monotherapy still reasonable?. International Journal of Clinical Practice 65:5, 531-535
CrossRef56
Alan D. Bell, André Roussin, Raymond Cartier, Wee Shian Chan, James D. Douketis, Anil Gupta, Maria E. Kraw, Thomas F. Lindsay, Michael P. Love, Neesh Pannu, Rémi Rabasa-Lhoret, Ashfaq Shuaib, Philip Teal, Pierre Théroux, Alexander G.G. Turpie, Robert C. Welsh, Jean-François Tanguay. (2011) The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines. Canadian Journal of Cardiology 27:3, S1-S59
CrossRef57
Monica Acciarresi, Paola De Rango, Francesca Romana Pezzella, Paola Santalucia, Serena Amici, Maurizio Paciaroni, Valeria Mommi, Giancarlo Agnelli, Valeria Caso. (2011) Secondary stroke prevention in women. Women's Health 7:3, 391-397
CrossRef58
Jonathan A. Rapp, Anil Verma, Tyrone J. Collins. 2011. Intracranial Vertebral Artery Stenting. , 427-435.
CrossRef59
James E. Frampton. (2011) Telmisartan. Drugs 71:6, 651-677
CrossRef60
Oscar R. Benavente, Carole L. White, Lesly Pearce, Pablo Pergola, Ana Roldan, Marie-France Benavente, Christopher Coffey, Leslie A. McClure, Jeff M. Szychowski, Robin Conwit, Patricia A. Heberling, George Howard, Carlos Bazan, Gabriela Vidal-Pergola, Robert Talbert, Robert G. Hart, . (2011) The Secondary Prevention of Small Subcortical Strokes (SPS3) study. International Journal of Stroke 6:2, 164-175
CrossRef61
Ronan Margey, Douglas E. Drachman. (2011) Carotid Artery Disease and Stenting: Insights From Recent Clinical Trials. Current Treatment Options in Cardiovascular Medicine 13:2, 129-145
CrossRef62
Alan D. Bell, André Roussin, Raymond Cartier, Wee Shian Chan, James D. Douketis, Anil Gupta, Maria E. Kraw, Thomas F. Lindsay, Michael P. Love, Neesh Pannu, Rémi Rabasa-Lhoret, Ashfaq Shuaib, Philip Teal, Pierre Théroux, A. Graham Turpie, Robert C. Welsh, Jean-François Tanguay. (2011) The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines Executive Summary. Canadian Journal of Cardiology 27:2, 208-221
CrossRef63
Sean P. Colgan. (2011) Adenosine and HIF1-alpha Signaling in Intestinal Hypoxic Injury and Recovery. Annual Review of Physiology 74:1, 110301101907077
CrossRef64
Ada Stefanescu, Stephen D. Wiviott. (2011) Considerations Regarding Antiplatelet Therapy in the Elderly. Current Cardiovascular Risk Reports 5:1, 86-95
CrossRef65
Denise H Rhoney. (2011) Contemporary Management of Transient Ischemic Attack: Role of the Pharmacist. Pharmacotherapy 31:2, 193-213
CrossRef66
Thomas G. Brott, Jonathan L. Halperin, Suhny Abbara, J. Michael Bacharach, John D. Barr, Ruth L. Bush, Christopher U. Cates, Mark A. Creager, Susan B. Fowler, Gary Friday, Vicki S. Hertzberg, E. Bruce McIff, Wesley S. Moore, Peter D. Panagos, Thomas S. Riles, Robert H. Rosenwasser, Allen J. Taylor. (2011) 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease. Journal of the American College of Cardiology 57:8, e16-e94
CrossRef67
Megan M. Donohue, David L. Tirschwell. (2011) Implications of Pharmacogenetic Testing for Patients Taking Warfarin or Clopidogrel. Current Neurology and Neuroscience Reports 11:1, 52-60
CrossRef68
Thomas G. Brott, Jonathan L. Halperin, Suhny Abbara, J. Michael Bacharach, John D. Barr, Ruth L. Bush, Christopher U. Cates, Mark A. Creager, Susan B. Fowler, Gary Friday, Vicki S. Hertzberg, E. Bruce McIff, Wesley S. Moore, Peter D. Panagos, Thomas S. Riles, Robert H. Rosenwasser, Allen J. Taylor. (2011) 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease: Executive Summary. Journal of the American College of Cardiology 57:8, 1002-1044
CrossRef69
Thalia S. Field, Oscar R. Benavente. (2011) Current Status of Antiplatelet Agents to Prevent Stroke. Current Neurology and Neuroscience Reports 11:1, 6-14
CrossRef70
Keun-Sik Hong. (2011) Measuring and Analysis of Outcome in Stroke Trials. Korean Journal of Stroke 13:1, 1
CrossRef71
Halvor Næss, Ulrike Waje-Andreassen, Jan Brøgger, Lars Thomassen. (2011) Pasienter med akutt hjerneinfarkt innlagt i slagenhet. Tidsskrift for Den norske legeforening 131:8, 814-818
CrossRef72
Harold P. Adams, Patricia H. Davis. 2011. Antithrombotic Therapy for Treatment of Acute Ischemic Stroke. , 971-991.
CrossRef73
Masafumi Ueno, Murali Kodali, Antonio Tello-Montoliu, Dominick Joseph Angiolillo. (2011) Role of Platelets and Antiplatelet Therapy in Cardiovascular Disease. Journal of Atherosclerosis and Thrombosis 18:6, 431-442
CrossRef74
Y. B
jot, M. Giroud, E. Touz
CrossRef75
Shinichiro Uchiyama, Yasuo Ikeda, Yasuhisa Urano, Yoshiharu Horie, Takenori Yamaguchi. (2011) The Japanese Aggrenox (Extended-Release Dipyridamole plus Aspirin) Stroke Prevention versus Aspirin Programme (JASAP) Study: A Randomized, Double-Blind, Controlled Trial. Cerebrovascular Diseases 31:6, 601-613
CrossRef76
Tatjana Rundek, Ralph L. Sacco. 2011. Prognosis after Stroke. , 219-241.
CrossRef77
Mar Castellanos, Babette B. Weksler, Oscar R. Benavente. 2011. Antiplatelet Therapy for Secondary Prevention of Stroke. , 1147-1172.
CrossRef78
Narayanaswamy Venketasubramanian, Joachim Röther, Deepak L. Bhatt, Blandine Pasquet, Jean-Louis Mas, Mark J. Alberts, Michael D. Hill, Franz Aichner, P. Gabriel Steg. (2011) Two-Year Vascular Event Rates in Patients with Symptomatic Cerebrovascular Disease: The REACH Registry. Cerebrovascular Diseases 32:3, 254-260
CrossRef79
Thomas G. Brott, Jonathan L. Halperin, Suhny Abbara, J. Michael Bacharach, John D. Barr, Ruth L. Bush, Christopher U. Cates, Mark A. Creager, Susan B. Fowler, Gary Friday, Vicki S. Hertzberg, E. Bruce McIff, Wesley S. Moore, Peter D. Panagos, Thomas S. Riles, Robert H. Rosenwasser, Allen J. Taylor, Alice K. Jacobs, Sidney C. Smith, Jeffery L. Anderson, Cynthia D. Adams, Nancy Albert, Christopher E. Buller, Mark A. Creager, Steven M. Ettinger, Robert A. Guyton, Jonathan L. Halperin, Judith S. Hochman, Sharon Ann Hunt, Harlan M. Krumholz, Frederick G. Kushner, Bruce W. Lytle, Rick A. Nishimura, E. Magnus Ohman, Richard L. Page, Barbara Riegel, William G. Stevenson, Lynn G. Tarkington, Clyde W. Yancy. (2011) 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease: Executive summary. Catheterization and Cardiovascular Interventionsn/a-n/a
CrossRef80
G.L. Moneta. (2011) Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis. Yearbook of Vascular Surgery 2011, 46-48
CrossRef81
G.L. Moneta. (2011) Clopidogrel Versus Dipyridamole in Addition to Aspirin in Reducing Embolization Detected With Ambulatory Transcranial Doppler: A Randomized Trial. Yearbook of Vascular Surgery 2011, 226-227
CrossRef82
Jessica M. Peña, Deepak L. Bhatt. 2011. Antiplatelet Therapy. , 69-85.
CrossRef83
Richard L. Harvey, Elliot J. Roth, David T. Yu, Pablo Celnik. 2011. Stroke Syndromes. , 1177-1222.
CrossRef84
M. Marcucci, A. Iorio, A. Nobili, M. Tettamanti, L. Pasina, A. Marengoni, F. Salerno, S. Corrao, P.M. Mannucci. (2010) Factors affecting adherence to guidelines for antithrombotic therapy in elderly patients with atrial fibrillation admitted to internal medicine wards. European Journal of Internal Medicine 21:6, 516-523
CrossRef85
D. Soonawala, R. A. Middelburg, M. Egger, J. P. Vandenbroucke, O. M. Dekkers. (2010) Efficacy of experimental treatments compared with standard treatments in non-inferiority trials: a meta-analysis of randomized controlled trials. International Journal of Epidemiology 39:6, 1567-1581
CrossRef86
Yumei Ye, Bo Long, Jinqiao Qian, Jose R. Perez-Polo, Yochai Birnbaum. (2010) Dipyridamole with Low-Dose Aspirin Augments the Infarct Size-Limiting Effects of Simvastatin. Cardiovascular Drugs and Therapy 24:5-6, 391-399
CrossRef87
R. Weber, B. Frank, H.-C. Diener. (2010) Antithrombotische und Antikoagulanzientherapie nach Schlaganfall und transitorisch ischämischer Attacke. Der Nervenarzt 81:12, 1509-1519
CrossRef88
H. S. Kirshner. (2010) Current issues in antiplatelet therapy for stroke prevention: the importance of stroke subtypes and differences between stroke and MI patients. Journal of Neurology 257:11, 1788-1797
CrossRef89
Hans-Christoph Diener, Christian Weimar, Ralph Weber. (2010) Antiplatelet therapy in secondary stroke prevention - state of the art. Journal of Cellular and Molecular Medicine 14:11, 2552-2560
CrossRef90
Zechariah G. Franks, Robert A. Campbell, Andrew S. Weyrich, Matthew T. Rondina. (2010) Platelet-leukocyte interactions link inflammatory and thromboembolic events in ischemic stroke. Annals of the New York Academy of Sciences 1207:1, 11-17
CrossRef91
Ralph Weber, Hans-Christoph Diener. (2010) Controversies and future perspectives of antiplatelet therapy in secondary stroke prevention. Journal of Cellular and Molecular Medicine 14:10, 2371-2380
CrossRef92
Yumei Ye, Jose R. Perez-Polo, Yochai Birnbaum. (2010) Protecting against ischemia-reperfusion injury: antiplatelet drugs, statins, and their potential interactions. Annals of the New York Academy of Sciences 1207:1, 76-82
CrossRef93
J. David Spence. (2010) Secondary stroke prevention. Nature Reviews Neurology
CrossRef94
M. Stramba-Badiale. (2010) Women and research on cardiovascular diseases in Europe: a report from the European Heart Health Strategy (EuroHeart) project. European Heart Journal 31:14, 1677-1681
CrossRef95
Sergio Coccheri. (2010) Antiplatelet Drugs – Do We Need New Options?. Drugs 70:7, 887-908
CrossRef96
James M. Gebel. (2010) Heterogeneity of Efficacy and Safety of Antiplatelet Therapy in Cardiovascular and Cerebrovascular Disease. American Journal Cardiovascular Drugs 10:2, 115-124
CrossRef97
Victor L. Serebruany. (2010) Clopidogrel and Heart Failure Survival. Journal of the American College of Cardiology 55:13, 1308-1309
CrossRef98
Graeme J Hankey, John W Eikelboom. (2010) Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events. The Lancet Neurology 9:3, 273-284
CrossRef99
Alan D. Michelson. (2010) Antiplatelet therapies for the treatment of cardiovascular disease. Nature Reviews Drug Discovery 9:2, 154-169
CrossRef100
Carl J. Pepine. (2010) Residual risk for secondary ischemic events in patients with atherothrombotic disease: Opportunity for future improvements in patient care. Annals of Medicine 42:1, 19-35
CrossRef101
Reinhard Dengler, Hans-Christoph Diener, Andreas Schwartz, Martin Grond, Helmut Schumacher, Thomas Machnig, Christoph Cyrill Eschenfelder, Joachim Leonard, Karin Weissenborn, Andreas Kastrup, Roman Haberl. (2010) Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial. The Lancet Neurology 9:2, 159-166
CrossRef102
Christine Lu-Emerson, David Likosky, Alpesh Amin, David Tirschwell. (2010) Management of ischemic stroke: Part 2. The inpatient stay. Journal of Hospital Medicine 5:2, 88-93
CrossRef103
Graeme J Hankey. (2010) Replacing aspirin and warfarin for secondary stroke prevention: is it worth the costs?. Current Opinion in Neurology 23:1, 65-72
CrossRef104
Clotilde Balucani, Kristian Barlinn, Zeljko Zivanovic, Lucilla Parnetti, Mauro Silvestrini, Andrei V. Alexandrov. (2010) Dual Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke: A Ghost from the Past or a New Frontier?. Stroke Research and Treatment 2010, 1-8
CrossRef105
Vijay K. Sharma. (2010) Transient ischemic attack associated with stenosis of accessory middle cerebral artery. Clinical Neurology and Neurosurgery 112:1, 88
CrossRef106
Dominick J. Angiolillo, Masafumi Ueno, Shinya Goto. (2010) Basic Principles of Platelet Biology and Clinical Implications. Circulation Journal 74:4, 597-607
CrossRef107
Joan F. Hilton. (2010) Noninferiority trial designs for odds ratios and risk differences. Statistics in Medicinen/a-n/a
CrossRef108
Timothy F. Kresowik, Harold P. Adams,. 2010. Cerebrovascular Disease. , 1424-1442.
CrossRef109
Asma M. Moheet, Irene Katzan. 2010. Stroke. , 878-882.
CrossRef110
R. Weber, K. Busch, H.C. Diener. (2009) Schlaganfallsekundärprävention bei Diabetespatienten. Der Diabetologe 5:8, 620-627
CrossRef111
Victor Serebruany, Ganesh Cherala, Craig Williams, Serge Surigin, Christopher Booze, Wiktor Kuliczkowski, Dan Atar. (2009) Association of platelet responsiveness with clopidogrel metabolism: Role of compliance in the assessment of “resistance”. American Heart Journal 158:6, 925-932
CrossRef112
D. Sander, T. Etgen. (2009) Sekundärprophylaxe des Schlaganfalls nach PRoFESS und SPARCL. Der Internist 50:11, 1227-1238
CrossRef113
Aamir Badruddin, Philip B. Gorelick. (2009) Antiplatelet therapy for prevention of recurrent stroke. Current Treatment Options in Neurology 11:6, 452-459
CrossRef114
Sarah Song, Bruce Ovbiagele. (2009) Management of risk factors for accelerated atherosclerosis. Current Treatment Options in Neurology 11:6, 460-472
CrossRef115
Nerses Sanossian, Bruce Ovbiagele. (2009) Prevention and management of stroke in very elderly patients. The Lancet Neurology 8:11, 1031-1041
CrossRef116
David Rigau Comas, José Álvarez-Sabin, Antonio Gil Núñez, Sonia Abilleira Castells, Francesc Xavier Borras Pérez, Pedro Armario García, Enrique Arrieta Antón, Eugenio Marañón Fernández, Juan Carlos Martí Canales, Ana Morales Ortiz, Juan Carlos Reverter Calatayud, Esther Sancristóbal Velasco, Ivan Solà Arnau, Pablo Alonso Coello. (2009) Guía de práctica clínica sobre prevención primaria y secundaria del ictus. Medicina Clínica 133:19, 754-762
CrossRef117
Cathie LM Sudlow, Gillian Mason, James B Maurice, Catherine J Wedderburn, Graeme J Hankey, Cathie LM Sudlow. 2009. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. .
CrossRef118
Holger K. Eltzschig. (2009) Adenosine: An Old Drug Newly Discovered. Anesthesiology 111:4, 904-915
CrossRef119
Christian Weimar, Ralph Weber, Hans-Christoph Diener. (2009) Antithrombotic medication for stroke prevention. Expert Review of Cardiovascular Therapy 7:10, 1245-1254
CrossRef120
B. Giannakopoulos, S. A. Krilis. (2009) How I treat the antiphospholipid syndrome. Blood 114:10, 2020-2030
CrossRef121
Niall JJ MacDougall, Sanjay Amarasinghe, Keith W Muir. (2009) Secondary prevention of stroke. Expert Review of Cardiovascular Therapy 7:9, 1103-1115
CrossRef122
Alexa N. Richie, Jorge Trejo, Christian G. Bowers, Rebecca B. McNeil, Dale M. Gamble, Sothear H. Luke, Robert D. Brown, Thomas G. Brott, Brett M. Kissela, Bradford B. Worrall, James F. Meschia. (2009) Joint Commission Primary Stroke Center Certification Does Not Affect Proband Enrollment: The Siblings With Ischemic Stroke Study. Journal of Stroke and Cerebrovascular Diseases 18:5, 363-366
CrossRef123
José Biller. (2009) Antiplatelet therapy in ischemic stroke: Variability in clinical trials and its impact on choosing the appropriate therapy. Journal of the Neurological Sciences 284:1-2, 1-9
CrossRef124
Thomas J. Kiernan, Bryan P. Yan, Michael R. Jaff. (2009) Antiplatelet therapy for the primary and secondary prevention of cerebrovascular events in patients with extracranial carotid artery disease. Journal of Vascular Surgery 50:2, 431-439
CrossRef125
Lonneke ML de Lau, Heleen M den Hertog, Evita G van den Herik, Peter J Koudstaal. (2009) Predicting and preventing stroke after transient ischemic attack. Expert Review of Neurotherapeutics 9:8, 1159-1170
CrossRef126
Sarah A Spinler. (2009) Safety and Tolerability of Antiplatelet Therapies for the Secondary Prevention of Atherothrombotic Disease. Pharmacotherapy 29:7, 812-821
CrossRef127
P. Kirchhof, J. Bax, C. Blomstrom-Lundquist, H. Calkins, A. J. Camm, R. Cappato, F. Cosio, H. Crijns, H.-C. Diener, A. Goette, C. W. Israel, K.-H. Kuck, G. Y.H. Lip, S. Nattel, R. L. Page, U. Ravens, U. Schotten, G. Steinbeck, P. Vardas, A. Waldo, K. Wegscheider, S. Willems, G. Breithardt. (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 11:7, 860-885
CrossRef128
M. Dieterich, G. F. Hamann. (2009) Bericht vom NeuroUpdate der Med-Update-Reihe in Wiesbaden (13./14.02.09). Der Nervenarzt 80:6, 720-724
CrossRef129
Gudrun Boysen. (2009) ACTIVE A: balancing the benefits and risks of clopidogrel and aspirin. The Lancet Neurology 8:6, 507-508
CrossRef130
Stuart J Pocock, James H Ware. (2009) Translating statistical findings into plain English. The Lancet 373:9679, 1926-1928
CrossRef131
Michael J. Schneck. (2009) Understanding the PRoFESS study for secondary stroke prevention. Current Treatment Options in Cardiovascular Medicine 11:3, 221-231
CrossRef132
Walter Van Mieghem. (2009) Prevention of major cardiovascular events with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker early or late after stroke. Journal of Hypertension 27:Suppl 2, S26-S31
CrossRef133
Larry B. Goldstein. (2009) New data about stenting versus endarterectomy for symptomatic carotid artery stenosis. Current Treatment Options in Cardiovascular Medicine 11:3, 232-240
CrossRef134
Taketoshi Ogawa, Masami Hashimoto, Yoichi Niitsu, Joseph A. Jakubowski, Yoshiro Tani, Ken-ichi Otsuguro, Fumitoshi Asai, Atsuhiro Sugidachi. (2009) Effects of prasugrel, a novel P2Y12 inhibitor, in rat models of cerebral and peripheral artery occlusive diseases. European Journal of Pharmacology 612:1-3, 29-34
CrossRef135
Steen Husted. (2009) Evidence-based prescribing and adherence to antiplatelet therapy—How much difference do they make to patients with atherothrombosis?. International Journal of Cardiology 134:2, 150-159
CrossRef136
A. Siddique, M. Butt, E. Shantsila, G. Y. H. Lip. (2009) New antiplatelet drugs: beyond aspirin and clopidogrel. International Journal of Clinical Practice 63:5, 776-789
CrossRef137
Javier Sanz, Pedro R. Moreno, Valentin Fuster. (2009) The Year in Atherothrombosis. Journal of the American College of Cardiology 53:15, 1326-1337
CrossRef138
M. Haris U. Usman, Lawrence A. Notaro, Rangadham Nagarakanti, Eric Brahin, Scott Dessain, Edward Gracely, Michael D. Ezekowitz. (2009) Combination Antiplatelet Therapy for Secondary Stroke Prevention: Enhanced Efficacy or Double Trouble?. The American Journal of Cardiology 103:8, 1107-1112
CrossRef139
Howard S. Kirshner. (2009) Differentiating ischemic stroke subtypes: Risk factors and secondary prevention. Journal of the Neurological Sciences 279:1-2, 1-8
CrossRef140
Helmi L. Lutsep. (2009) Recent Clinical Trials of Antiplatelet Therapy in Secondary Stroke Prevention: Expectations and Results for Application in Primary Care Settings. The American Journal of Medicine 122:4, S21-S31
CrossRef141
M. Cohen. (2009) Expanding the Recognition and Assessment of Bleeding Events Associated With Antiplatelet Therapy in Primary Care. Mayo Clinic Proceedings 84:2, 149-160
CrossRef142
Masakatsu NISHIKAWA, Satoshi TAMARU. (2009) 1. Molecular Mechanisms and Characteristics of Antiplatelet Drugs. Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics 40:6, 253-260
CrossRef143
B. L. Cucchiara. (2009) Evaluation and management of stroke. Hematology 2009:1, 293-301
CrossRef144
Jens Minnerup, Wolf-Rüdiger Schäbitz. (2009) Multifunctional actions of approved and candidate stroke drugs. Neurotherapeutics 6:1, 43-52
CrossRef145
Kazunori Toyoda. (2009) Pharmacotherapy for the Secondary Prevention of Stroke. Drugs 69:6, 633-647
CrossRef146
Cheryl D. Bushnell, Cathleen S. Colón-Emeric. (2009) Secondary Stroke Prevention Strategies for the Oldest Patients. Drugs & Aging 26:3, 209-230
CrossRef147
H. P. Adams. (2009) Secondary Prevention of Atherothrombotic Events After Ischemic Stroke. Mayo Clinic Proceedings 84:1, 43-51
CrossRef148
2009. Recommandations de lecture. , 219-221.
CrossRef149
A. Rabinstein. (2009) Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. Yearbook of Neurology and Neurosurgery 2009, 18-21
CrossRef150
Nina C Raju, John W Eikelboom, Jack Hirsh. (2008) Platelet ADP-receptor antagonists for cardiovascular disease: past, present and future. Nature Clinical Practice Cardiovascular Medicine 5:12, 766-780
CrossRef151
Graeme J Hankey, John W Eikelboom. (2008) What do the results of the PRoFESS trial teach us?. The Lancet Neurology 7:10, 860-862
CrossRef152
Hans-Christoph Diener, Ralph L Sacco, Salim Yusuf, Daniel Cotton, Stephanie Ôunpuu, William A Lawton, Yuko Palesch, Reneé H Martin, Gregory W Albers, Philip Bath, Natan Bornstein, Bernard PL Chan, Sien-Tsong Chen, Luis Cunha, Björn Dahlöf, Jacques De Keyser, Geoffrey A Donnan, Conrado Estol, Philip Gorelick, Vivian Gu, Karin Hermansson, Lutz Hilbrich, Markku Kaste, Chuanzhen Lu, Thomas Machnig, Prem Pais, Robin Roberts, Veronika Skvortsova, Philip Teal, Danilo Toni, Cam VanderMaelen, Thor Voigt, Michael Weber, Byung-Woo Yoon. (2008) 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 7:10, 875-884
CrossRef153
Kent, David M., Thaler, David E., . (2008) Stroke Prevention — Insights from Incoherence. New England Journal of Medicine 359:12, 1287-1289
Full Text154
Norio Tanahashi. (2008) Antiplatelet agents for ischemic stroke: current status and future directions. Nosotchu 30:6, 834-840
CrossRef
