Original Article
A Comparison of Two Doses of Aspirin (30 mg vs. 283 mg a Day) in Patients after a Transient Ischemic Attack or Minor Ischemic Stroke
N Engl J Med 1991; 325:1261-1266October 31, 1991
- Abstract
- Abstract
Background.
Aspirin is known to improve the outcome of patients who have had a cerebral transient ischemic attack, but the optimal dose of aspirin remains uncertain. Experimental evidence indicates that 30 mg of aspirin daily alters platelet aggregation more favorably than the 300-mg dose currently used in patients after transient ischemic attack or minor ischemic stroke.
Methods.
We assessed the effects of two doses of a water-soluble preparation of acetylsalicylic acid, or aspirin (30 mg vs. 283 mg a day), on the occurrence of death from all vascular causes, nonfatal stroke, or nonfatal myocardial infarction in a double-blind, randomized, controlled clinical trial in patients who had had a transient ischemic attack or minor stroke. A total of 3131 patients participated in the study. The mean follow-up was 2.6 years.
Results.
In the group assigned to receive 30 mg of aspirin, the frequency of death from vascular causes, nonfatal stroke, or nonfatal myocardial infarction was 228 of 1555 (14.7 percent), as compared with 240 of 1576 (15.2 percent) in the group assigned to receive 283 mg. The age- and sex-adjusted hazard ratio for the group receiving the lower dose was 0.91 (95 percent confidence interval, 0.76 to 1.09). There were slightly fewer major bleeding complications in the 30-mg group than in the 283-mg group (40 vs. 53), and significantly fewer reports of minor bleeding (49 vs. 84). Fewer patients receiving 30 mg of aspirin reported gastrointestinal symptoms (164 vs. 179) and other adverse effects (73 vs. 90).
Conclusions.
Our data indicate that 30 mg of aspirin daily is no less effective in the prevention of vascular events than a 283-mg dose in patients with a transient ischemic attack or minor stroke, and has fewer adverse effects. (N Engl J Med 1991;325:1261–6.)
Media in This Article
Figure 1
Kaplan–Meier Curves for the Combined Outcome Event of Death from Vascular Causes, Nonfatal Stroke, or Nonfatal Myocardial Infarction, According to Assigned Treatment.Table 1
Base-Line Characteristics of the Study Patients, According to Assigned Treatment.Article Activity
- Article
PATIENTS who have a transient ischemic attack or nondisabling ischemic stroke have an annual risk of death from all vascular causes, nonfatal stroke, or nonfatal myocardial infarction of 7 to 12 percent.1 2 3 4 An overview by the Antiplatelet Trialists' Collaboration Group indicated that treatment with medium or high doses of aspirin (300 to 1500 mg per day) reduces the incidence of these vascular events by 20 to 25 percent.3 A dose of 300 mg of aspirin per day is a commonly accepted standard therapy after a transient ischemic attack or minor ischemic stroke.2 A dose of 30 mg per day, however, might be even more effective, because the inhibition of aggregation caused by the diminished production of thromboxane A2 in platelets is still complete, whereas the production of prostacyclin, which has an antiaggregation effect, is little affected in endothelial cells.6 7 8
The Dutch TIA Trial was a double-blind, randomized, controlled clinical trial involving two treatment comparisons in patients with a transient ischemic attack or minor ischemic stroke. In the aspirin study we investigated whether a low dose (30 mg per day, the study treatment) is more effective than a medium dose (283 mg per day, the conventional treatment2) in preventing death from vascular causes, nonfatal stroke, and nonfatal myocardial infarction. In the beta-blocker study we analyzed whether 50 mg of atenolol per day, as compared with placebo, reduced the occurrence of the same outcome events. The methods of the study have been described in detail elsewhere9; in this paper the main results of the aspirin study regarding efficacy and safety are reported.
Methods
Eligible Patients
Patients who were seen by a neurologist at 1 of the 63 collaborating centers9 (see Appendix) between February 28, 1986, and March 3, 1989, were eligible for the trial if they had had a transient ischemic attack (symptoms lasting for less than 24 hours) or minor ischemic stroke (symptoms persisting for more than 24 hours) within the preceding three months. Patients with stroke had to be independent in most of their daily activities (grade on modified Rankin Scale, 3 or less).10 , 11 Patients with cerebral ischemia due to identifiable causes other than arterial thrombosis or arterial embolism, including atrial fibrillation, cardiac valve disease, a recent myocardial infarction, and disorders of blood coagulation, were excluded. The study protocol was approved by the institutional review boards of the participating hospitals. All the patients were informed about the background and procedures of the trial, both through discussion and by means of a printed information sheet, and all gave their explicit consent.
Base-Line Characteristics
To obtain information on neurologic symptoms as reliably as possible, a checklist in easily understood language was used.12 The list contained a number of detailed multiple-choice questions about the nature of any symptoms and the time course, including the mode of onset, synchronicity of the symptoms, duration of the attack, mode of disappearance, and number of attacks.
Apart from the specific history, we recorded demographic data, vascular risk factors, vascular history, and medications. Computed tomography (CT) of the brain was required in all patients except those with transient monocular blindness.
Treatment
Patients were randomized unless they had a contraindication to or an absolute indication for a specific dose of aspirin. A total of 3131 patients were enrolled, of whom 1454 also participated in the atenolol study. Balance between treatment assignments within hospitals was achieved with the use of random permutated blocks; blinded randomization codes were distributed by telephone.
Aspirin was supplied as pulverized carbaspirin calcium, a soluble complex of equimolar quantities of urea and the calcium salt of aspirin (Ascal) in doses of 38 mg and 360 mg, equivalent to 30 mg and 283 mg of aspirin, respectively, and mixed with filler to produce identical powders that were to be dispersed in water and taken before breakfast. The patients were advised to take only acetaminophen as an analgesic agent.
A previous pharmacokinetic comparison of equimolar doses of carbaspirin calcium and plain aspirin showed no important differences with regard to bioavailability.13 In 31 study patients who had been receiving the trial medication for an average of 17 months we measured serum thromboxane B2 levels; the study pharmacist decoded the treatment assignments without disclosing names. Both in the patients taking 30 mg of aspirin and in those taking 283 mg a reduction of more than 99 percent in thromboxane B2 synthesis was observed, as compared with normal values.7
Follow-up
Every four months, independently of the continuation of trial medication, all the patients were seen by their neurologists or, if the patients could not attend the hospital clinic, by their general practitioners. Both neurologists and general practitioners were blinded to treatment assignment. We determined the occurrence of transient ischemic attacks, outcome events (see below), vascular diseases, vascular surgery, changes in medication, or possible adverse effects; the blood pressure; and the modified Rankin grade at each visit. The physicians who followed the patients were asked to include all causes of disability and handicap in the final Rankin grade, including coexistent diseases.11 All the patients had their last follow-up visit between March 1 and June 30, 1990; the mean duration of follow-up was 31 months, with a minimum of 12 and a maximum of 52 months. No patient was lost to follow-up.
Outcome Events
The primary outcome event was the combined event of death from all vascular causes, nonfatal stroke, or nonfatal myocardial infarction, whichever happened first. Secondary outcome events were death from all causes, death from vascular causes, and death from vascular causes or nonfatal stroke. The combination of fatal and nonfatal stroke was considered a tertiary outcome event. No separate analyses of nonfatal events were planned.
The definition of death from vascular causes included sudden death (unexpected cardiac death occurring within 1 hour after onset of symptoms, or within 24 hours given convincing circumstantial evidence) or death from stroke, myocardial infarction, congestive heart failure, or systemic bleeding. For the diagnosis of nonfatal stroke, relevant clinical features persisting for more than 24 hours had to correspond with a new infarction or a hemorrhage on a repeated CT scan. If sudden and focal neurologic deficits without CT changes (or in the absence of a CT scan) caused an increase in handicap of at least one grade on the modified Rankin Scale, the event was also classified as a stroke. Myocardial infarction had to be documented by at least two of the following characteristics: a history of chest discomfort, specific cardiac enzyme levels more than twice the upper limit of normal, or the development of Q waves on the standard 12-lead electrocardiogram. All outcome events were independently classified by at least three members of the Auditing Committee for Outcome Events9 (Appendix), without knowledge of the patients' treatment assignments.
A second type of analysis was aimed at the changes in handicap due to all causes as graded on the modified Rankin Scale.10 , 11 For this purpose, the Rankin grades at randomization and at the last follow-up visit were compared.
Adverse Effects
The occurrence of bleeding complications was recorded for all patients. Fatal bleeding had to be documented by convincing clinical evidence or autopsy. Nonfatal episodes of bleeding were considered major if a hospital visit and treatment were necessary. Epistaxis, easy bruising, and melena were regarded as minor bleeding if no treatment was required. All major bleeding complications were reviewed by the Executive Committee, without knowledge of the patients' treatment assignments.
All adverse effects were recorded as reported by the patients; the physician inquired about such effects in a general fashion.
Interim Analysis
Interim data were submitted to the Monitoring Committee (Appendix) 17, 24, 36, and 45 months after the start of the trial; a stopping rule of 3 SD was used.14 The unblinded but aggregated data were provided by the trial coordinator and the pharmacist on the Steering Committee (Appendix), leaving the other members of the committee uninvolved; the pharmacist was the only person who had access to the treatment codes of individual patients during the trial.
Statistical Analysis
The principal aim of the statistical analysis was to compare the incidence of the primary outcome event between the two treatment groups. Kaplan–Meier curves were used for graphic comparison.15 The occurrence of outcome events was compared in terms of the hazard ratio — i.e., the risk of the outcome event per unit of time for patients randomly assigned to 30 mg of aspirin daily divided by the risk for those randomly assigned to 283 mg of aspirin daily. Hazard ratios were obtained with use of the Cox proportional-hazards model16 and adjusted for base-line incomparability (Egret statistical package17). The precision of the hazard-ratio estimates was described by means of 95 percent confidence intervals obtained from the Cox model. Subgroup analyses were planned in advance. Statistical differences between the hazard ratios of subgroups were determined by means of the coefficient and its standard deviation of the interaction term of treatment and the subgroup factor in the Cox model. The primary data analysis was based on the intention-to-treat principle: whether medication was taken or not, the patients were analyzed according to their originally assigned treatment until the last follow-up visit. In addition, we performed analyses of patients who continued to receive treatment (treatment analyses), in which we included only the outcome events that occurred while study treatment was being taken or before the 28th day after the discontinuation of the treatment. The 23 patients who were inappropriately enrolled in the trial, because they had brain diseases other than ischemia (14 had a brain tumor, 4 an intracerebral hemorrhage, and 5 other diseases), were included in the intention-to-treat analysis but excluded from the treatment analysis.
Results
Table 1 shows the base-line characteristics of the 3131 patients, according to assigned treatment. One third of the patients were women; there was a slight excess of men and of patients over 65 years old in the group receiving 30 mg of aspirin a day. The qualifying event for the trial was a transient ischemic attack in one third of the patients and a minor ischemic stroke in two thirds. Three quarters of the patients were randomized within one month of the qualifying event.
After three years, 82 percent of the surviving patients were still using the trial medication; this number was 91 percent after one year (Table 2Table 2
When and Why Trial Medication Was Discontinued in the Study Patients.). The main reasons for discontinuation were the occurrence of a nonfatal outcome event (although the participating physicians were strongly encouraged to continue the trial drug if possible), an adverse effect, the start of anticoagulant drugs (usually after vascular surgery, atrial fibrillation, or deep-vein thrombosis), or the patient's request; there were no significant differences between the treatment groups in the frequency of these reasons.Figure 1Figure 1
Kaplan–Meier Curves for the Combined Outcome Event of Death from Vascular Causes, Nonfatal Stroke, or Nonfatal Myocardial Infarction, According to Assigned Treatment. shows Kaplan–Meier curves for the primary outcome event. Table 3Table 3
Occurrence of First Outcome Events, According to Assigned Treatment.* shows the occurrence of first outcome events according to assigned treatment, on the basis of intention-to-treat analysis. Sixty-eight percent of all deaths were of vascular origin (43 percent cardiac, 18 percent cerebral, and 7 percent other). The age- and sex-adjusted hazard ratio (0.91) was slightly smaller than its crude analogue, because the slight imbalance in randomization with regard to age and sex was to the disadvantage of the 30-mg group. Adjustment for other base-line characteristics had no influence on the estimates of effects. The crude hazard ratio for fatal and nonfatal stroke was 0.82, with a 95 percent confidence interval of 0.64 to 1.04. Crude hazard ratios calculated according to the treatment analysis differed little from those of the intention-to-treat analysis; for the combined primary outcome event of the study — death from vascular causes, nonfatal stroke, or nonfatal myocardial infarction — the hazard ratio according to the treatment analysis was 0.92.Forty patients receiving 30 mg of aspirin had one or more major bleeding complications, as compared with 53 patients receiving the 283-mg dose (hazard ratio, 0.77; 95 percent confidence interval, 0.51 to 1.16) (Table 4Table 4
Incidence of Adverse Effects, According to Assigned Treatment.*). There were 11 episodes of fatal bleeding in the 30-mg group and 18 in the 283-mg group. When the analysis was restricted to patients actually receiving treatment, the numbers of major bleeding complications were 35 and 42, respectively (hazard ratio, 0.84; 95 percent confidence interval, 0.53 to 1.31). Episodes of minor bleeding were significantly more common in the patients receiving the 283-mg dose (Table 4). Gastric discomfort and other adverse effects were both more frequent in the 283-mg group, although no statistically significant difference was found. Taken together, there was a 17 percent reduction in the incidence of minor bleeding, gastric discomfort, and other minor adverse effects in the low-dose group (95 percent confidence interval, 2 to 30 percent; 258 vs. 310). Hazard ratios calculated according to the treatment analysis differed little from those of the intention-to-treat analysis.None of the planned subgroup analyses for the primary outcome event — i.e., according to sex, age, presence of ischemic heart disease (history of angina or previous myocardial infarction or abnormal Q waves on the 12-lead electrocardiogram), type of qualifying event, and atenolol assignment — showed a statistical difference between the hazard ratios of the subgroups. In particular, among the patients who also participated in the atenolol study, no significant difference was observed between the aspirin hazard ratios of patients receiving 50 mg of atenolol and those receiving placebo (hazard ratios, 0.99 and 0.88, respectively; P = 0.69). The most pronounced difference was observed between men and women (hazard ratios, 1.04 and 0.73, respectively; P = 0.10).
The direction of the changes in Rankin grade between the start of the trial and the last follow-up visit or death revealed little difference between the two aspirin groups.
Discussion
Principal Results
Our findings indicate that a low dose of aspirin (30 mg) is no less effective than a medium dose (283 mg) in the prevention of the composite outcome event of death from vascular causes, nonfatal stroke, or nonfatal myocardial infarction (age- and sex-adjusted hazard ratio, 0.91; 95 percent confidence interval, 0.76 to 1.09), and it causes fewer adverse effects. That doses of aspirin of about 300 mg are more effective than placebo can be inferred from the overview of all controlled trials with antiplatelet agents — mostly aspirin — performed before 1987.5 This overview found a mean (±SD) odds reduction of 25±3 percent for the same composite outcome event in patients with various forms of arterial disease (cardiac, cerebral, or peripheral), with no significant difference between doses of approximately 300 mg and 1000 mg of aspirin. The United Kingdom Transient Ischaemic Attack Aspirin Trial is the only study that directly compared a dose of 300 mg of aspirin with placebo in patients with cerebrovascular disease, and it showed a 12 percent reduction in risk (95 percent confidence interval, —5 to 27)2; if this study is combined with placebo-controlled trials of 300 mg of aspirin after myocardial infarction, the mean (±SD) reduction in risk was 24±8 percent.5 More recently, in the Second International Study of Infarct Survival, a dose of 160 mg of aspirin not only reduced 5-week mortality from vascular causes in patients with acute myocardial infarction by 21 percent (95 percent confidence interval, 13 to 37), but it also significantly reduced the incidence of nonfatal stroke (and reinfarction) during and after hospitalization (mean follow-up, 15 months).19 For other indications, doses lower than 300 mg also had a beneficial effect.20 , 21 The event rate for death from vascular causes or nonfatal stroke in our trial (5.3 per 100 person-years) was similar to that in the United Kingdom trial (5.0)2 and lower than that in the European Stroke Prevention Study (8.0).1 , 5
Adverse Effects
The incidence of major bleeding complications was low in both study groups (2.6 percent in the 30-mg group and 3.2 percent in the 283-mg group), but we included only episodes of bleeding that required a hospital visit and treatment. These criteria for major bleeding complications were the most practical, because information had to be obtained retrospectively and from hospitals that were not all participating in the trial. The difference between groups showed a trend in favor of the lower dose but was not statistically significant. Primary intracerebral hemorrhages were found in 26 (10 percent) of the 273 patients who had a stroke as the first event during follow-up; this proportion is more accurate than in previous studies, because of the high rate of CT scanning (85 percent) in patients with cerebral events. There were significantly fewer episodes of minor bleeding in patients taking the lower dose (3.2 percent vs. 5.3 percent), and an equally small number of episodes of minor gastrointestinal bleeding in both groups. These results were unexpected, inasmuch as one would anticipate a similar incidence of bleeding with doses of the drug that suppress thromboxane-dependent platelet function with equal effectiveness. The explanation may be that higher doses of aspirin enhance bleeding independently of the acetylation of cyclooxygenase.22 Taken together, minor bleeding complications, gastric discomfort, and ill-defined adverse effects occurred significantly less often with the lower dose of aspirin (risk reduction, 17 percent; 95 percent confidence interval, 2 to 30). By comparison, among the patients in the United Kingdom trial who were treated with 300 mg of aspirin, 4 percent reported gastrointestinal bleeding (as compared with 2 percent of those receiving placebo), 1.5 percent required admission to the hospital (placebo, 1 percent), and 35 percent had other gastrointestinal symptoms (placebo, 27 percent).2
Theoretical Implications
The results of our trial have at least three implications for the understanding of aspirin's effects on the function of platelets, arterial endothelium, and gastric mucosa. First, it is well known that — at least after a few days — a dose of 30 mg of aspirin a day inhibits the production of thromboxane A2 in platelets to the same degree (more than 95 percent) as standard doses of 300 mg or more, by virtue of cumulative acetylation of cyclooxygenase.7 , 8 , 23 The fact that the clinical effects of the two doses are also similar with regard to the prevention of arterial thromboembolism supports the notion that the protective action of aspirin is indeed mediated by the inactivation of platelet cyclooxygenase. Second, the fact that the lower dose spares cyclooxygenase outside platelets and leaves the production of prostacyclin by arterial endothelium largely unaffected24 , 25 has no detectable clinical relevance to the prevention of arterial thromboembolism. Nevertheless, the confidence interval for the hazard ratio is compatible with a 20 to 25 percent reduction in risk with the 30-mg dose, as compared with the 283-mg dose. This may give a rough estimate of the maximal benefit to be derived from the biochemical selectivity of low-dose aspirin for the design of future studies. Third, the lower incidence of gastrointestinal adverse effects with the 30-mg dose may reflect a substantial sparing of cyclooxygenase in the gastric mucosa.23 The selective inhibition of platelet cyclooxygenase can be attributed to the capacity of nucleated cells to synthesize the enzyme de novo, and also to the presystemic acetylation of platelets.26 , 27
Practical Implications
With doses of aspirin as low as 30 mg, it takes several days to achieve the maximal degree of platelet inhibition.23 It is therefore advisable to start treatment with a loading dose of at least 120 mg.23 Most of the patients in this trial were receiving provisional treatment with doses of about 300 mg for a few days before the investigations and consent procedure preceding randomization had been completed. The results in our trial were obtained with a fixed dose of 38 mg of carbaspirin calcium (Ascal) containing 30 mg of aspirin. This formulation of aspirin was selected because gastric discomfort is relatively infrequent. Carbaspirin calcium (unlike plain aspirin) is freely soluble in water, which may be of critical importance in the absorption of low doses of aspirin. The bioavailability and bioequivalence of the two preparations do not seem to differ according to our results and those of others.13
Address reprint requests to Dr. Jan van Gijn at the University Department of Neurology, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, the Netherlands.
Supported by grants from the Netherlands Heart Foundation (84.089 and 88.210); the Praeventiefonds (28–1732); ICI-Farma, the Netherlands; ICI Pharmaceuticals, United Kingdom; Dagra-Pharma (previously ACF—Chemiefarma), the Netherlands; and University Hospital Utrecht.
*The members of the Writing Committee were as follows: Jan van Gijn, M.D., University of Utrecht (chairman); Ale Algra, M.D., University of Utrecht (co-chairman); Jaap Kappelle, M.D., University of Utrecht; Peter J. Koudstaal, M.D., University Hospital Rotterdam; and Anet van Latum, M.D., Erasmus University Rotterdam. Other study participants are listed in the Appendix.
We are indebted to Drs. H.P. Adams, M. Gent, C. Patrono, J.G.P. Tijssen, and C.P. Warlow for helpful comments during the preparation of this article.
Appendix
Participating centers (with number of patients randomized and principal investigators): De Wever Ziekenhuis Heerlen (324; C.L. Franke,* C.J. Hagen, P.J.J. Koehler, J.F. Mirandolle); Academisch Ziekenhuis Dijkzigt Rotterdam (293; W.J.J.F. Hoppenbrouwers, G. de Jong, P.J. Koudstaal,* A. Staal,* M. Vermeulen*); Canisius-Wilhelmina Ziekenhuis Nijmegen (221; H.J.J.A. Bernsen, C.W.G.M. Frenken,* H.J.M.M. Lohmann, E.F.J. Poels, M.J.J. Prick, W.I.M. Verhagen, C.J.W. van de Vlasakker, E.V. van Zuilen); Academisch Ziekenhuis Utrecht (208; J. van Gijn,* J.J. Jansen, L.J. Kappelle,* J.M.J. Krul, W. Weststrate); St. Franciscus Gasthuis Rotterdam (170; P.R. Beneder, C. Bulens,* L.H. Penning de Vries-Bos); St. Geertruiden—St. Jozefziekenhuis Deventer (125; J.A. van Beeck, W.J. Feikema, J.H.M. van Gasteren, N.A.C. Roelvink, A.N. Veltema, C.J.M. Vredeveld); Diaconessenhuis Leiden (107; P.E. Briët, J. van Rossum); Academisch Ziekenhuis Maastricht (103; J. Boiten, J. Lodder, P.J.M. van der Lugt); Academisch Medisch Centrum Amsterdam (100; H. van Crevel,* D. Herderscheê, A. Hijdra*); St. Lucasziekenhuis Amsterdam (100; J.A.L. Vanneste, J. Vos); Ziekenhuis Ziekenzorg Enschede (83; E.N.H. Jansen, J. Troost); Twenteborg Ziekenhuis, Almelo (78; J.W.M. ter Berg); Westeinde Ziekenhuis 's-Gravenhage (76; A. Boon, J. Hilbers, J. Nihom, J.T.J. Tans); St. Elisabeth Ziekenhuis Tilburg (74; A.A.W. Op de Coul, A.C.M. Leyten, R.L.A.A. Schellens, C.C. Tijssen); Stichting Oosterscheldeziekenhuizen, Goes (73; A.M. Boon, W.H.G. Lieuwens); Ziekenhuis Gelderse Vallei, Ede (65; M.G. Smits, A.J.M. Vos); St. Maartens Gasthuis Venlo (62;
*Member of the Steering Committee and the Auditing Committee for Outcome Events. G.D.M. van Hellemondt, B.J. Meems, T.G. Segeren); Merwedeziekenhuis Dordrecht (54; P.A.Th. Carbaat, L.I. Hertzberger, C.S.D. Hoekstein [deceased]); Ziekenhuis Lievensberg Bergen op Zoom (53; P.J.I.M. Berntsen); St. Joseph Ziekenhuis Eindhoven (52; B.J. van Kasteren, L.H.Th.S. Kortbeek, P.M.G.A.W. Mulkens); Diaconessenhuis Eindhoven (48; W. Groeneveld, H.J. Troelstra, A.J. Vermeij); Refajaziekenhuis Dordrecht (44; J.J. Groen, C. Oppelaar); Elisabeth Gasthuis Haarlem (40; J.A.M. Kuster, L. de Vries); Streekziekenhuis Midden Twente Hengelo (39; M.M. Klaver); Hervormd Diaconessenhuis Arnhem (38; H. Becker, F.A. Jongebloed); St. Elisabethziekenhuis Leiderdorp (37; A.J.P. Boesten, F.J.J. Prick, H.G.S. Snijder, M.M. Veering, R.J.W. Witteveen); Medisch Centrum Alkmaar (36; J.W.W.H. Dammers, R. ten Houten, J.A. van Leusden, H.J.S. Straatman); Ziekenhuis St. Jansdal Harderwijk (35; M.J.P. Muller Kobold, R.Th. Schoenmaker); Holy Ziekenhuis Vlaardingen (35; J.J.M. Driesen, W.F. van Oudenaarden, H.G.J. Krouwer, J.C.B. Verhey); Zuiderzee Ziekenhuis Lelystad (32; J.P. Geervliet, E. Siebenga); Diaconessenhuis Voorburg (30; J.L. van Doorn, G.J. de Jong); Hofpoort Ziekenhuis Woerden (25; R. Wielaard, E.J. Wieringa); Academisch Ziekenhuis Leiden (23; O.J.S. Buruma, G.W.A.M. Padberg, A.C.B. Peters, R.A.Chr. Roos, A.R. Wintzen); Bergweg Ziekenhuis Rotterdam (22; R. Gelsema, Th.C.M. van Woerkom); Medisch Centrum Leeuwarden (21; J.G. de Bruijn, J.C. den Heyer, J.G. Koster); St. Clara Ziekenhuis Rotterdam (21; H.J. van den Brand, C.A. van Donselaar, H.A.W. Sinnige, J.A.G. Strijbosch, J.G. van Woerkom); Ziekenhuis Nij Smellinghe Drachten (18; H.L. van der Wiel); St. Anna Ziekenhuis Geldrop (18; T.J.M. Breuer, P.F.M. Houben); St. Franciscus Ziekenhuis Roosendaal (14; F.P.A.M. Schlosser, A.C.G.A. van Spreeken, G.A.M. Verheul); Diaconessenhuis Heemstede (14; R.H. Groen, J.O. Mispelblom Beyer); Medisch Centrum Leeuwarden, locatie Bonifatius (12; J. Dijkstra); Diaconessenhuis Utrecht (11; D.N.J. Donker); Maria Ziekenhuis Tilburg (10; J.G. Eerenberg, H.J.M. van der Leeuw, C.C. Tijssen); Ziekenhuis Malberg Arnhem (9; L. van der Graaff, G. Schouwink); Beatrixziekenhuis Gorinchem (9; M.H. Dijkman, P.M. Stuurman); St. Lucas Ziekenhuis Winschoten (9; J.B. van der Gaast); St. Elizabethziekenhuis Amersfoort (8; R. Bijlsma, M.B.M. Vermeulen); Catharina Ziekenhuis Eindhoven (8; J.N. Berendes); Medisch Spectrum Twente, locatie Ariënsplein, Enschede (8; H. Solleveld); Van Weel—Bethesda Ziekenhuis Dirksland (8; U.W. Huisman); Havenziekenhuis Rotterdam (6; J.Z. van den Berg, H.J. Vroon); Schieland Ziekenhuis Schiedam (6; R. Agema, W.C. Baard); van Dam—Bethesda Ziekenhuis Rotterdam (5; A. van der Zwart); Eudokia Rotterdam (5; A.H.C. Geerlings, A.T. Tjiam); Ziekenhuis Rivierenland Tiel (5; M.G. Baal, P.J. de Jong); Ziekenhuis De Lichtenberg Amersfoort (4; C. Boutkan, J.L. van der Zwan); Ikazia Ziekenhuis Rotterdam (4; L.J.M.M. Mulder); Streekziekenhuis Oranjeoord Harlingen (3; G.S.D. van Leersum); Stichting Streekziekenhuis Hilversum, locatie Koningsstraat (3; F.A.M. Zandhuis); Antoniushove Leidschendam (2; C.H. Terpstra, A. Verkijk); St. Antonius Ziekenhuis Sneek (2; P.J.H.W. Jansen, J.D.M. van der Meulen); St. Jozefziekenhuis Gouda (1; A. Aanen); Streekziekenhuis West-Friesland Hoorn (1; H.B. Grolman-Kovarova).
Other contributors: A. Algra, University of Utrecht; G.S. Baarsma, Eye Infirmary Rotterdam (Advisory Board, Auditing Committee for Outcome Events); R.W. Brower, Rotterdam (Advisory Board); B.J.M. Delemarre, Academic Medical Center Amsterdam (Auditing Committee); H. Frericks, University of Utrecht (Executive Committee); J.H. Glerum, University Hospital Utrecht (Advisory Board); Y. van der Graaf, University of Utrecht (Advisory Board); P.G. Hugenholtz, Erasmus University Rotterdam (Advisory Board); G. de Jong, University Hospital Rotterdam (ECG Committee); J.C. van Latum, Erasmus University Rotterdam; J. Lubsen, Erasmus University Rotterdam (Advisory Board); G.T. Meester, University of Utrecht (Advisory Board); R. Peto, University of Oxford (Monitoring Committee); G.A.M. Pop, University Hospital Rotterdam (ECG Committee, Auditing Committee); L.M.P. Ramos, University Hospital Utrecht (CT Scan Committee); A.F.A.M. Schobben, University Hospital Utrecht (Executive Committee, Steering Committee); J.J. Sixma, University of Utrecht (Advisory Board); J.G.P. Tijssen, Academic Medical Center Amsterdam (Advisory Board); F.W.A. Verheugt, Free University of Amsterdam (ECG Committee, Auditing Committee); F. van Vliet (data manager); C.P. Warlow, University of Edinburgh (Monitoring Committee).
- References
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The RISC Group.
CrossRef | Web of Science | Medline21
Wallenburg
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Gaspari
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Patrono
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FitzGerald
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Benigni
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Pedersen
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Pedersen
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- Citing Articles (178)
Citing Articles
1
Michael Erbach, Hellmut Mehnert, Oliver Schnell. (2012) Diabetes and the risk for colorectal cancer. Journal of Diabetes and its Complications
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Paul A. Gurbel, Udaya S. Tantry. 2011. Resistance to Antiplatelet Therapy. .
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Adnan H. Siddiqui, Sabareesh K. Natarajan, L. Nelson Hopkins, Elad I. Levy. (2011) Carotid Artery Stenting for Primary and Secondary Stroke Prevention. World Neurosurgery 76:6, S40-S59
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Maria Czarina Acelajado, Suzanne Oparil. (2011) Antiplatelet Therapy for Transient Ischemic Attack. The Journal of Clinical Hypertensionno-no
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Rubén Casado-Arroyo, María Muñoz-Villalenguas, Ángel Lanas Arbeloa. (2011) Antiagregantes plaquetarios e inhibidores de la bomba de protones. ¿Cómo optimizar el riesgo-beneficio en los pacientes con riesgo cardiovascular y riesgo de hemorragia gastrointestinal?. Gastroenterología y Hepatología 34:7, 478-491
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J. Donald Easton. (2011) Antithrombotic Management for Transient Ischemic Attack and Ischemic Stroke (Other than Atrial Fibrillation). Current Atherosclerosis Reports 13:4, 314-320
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X. Garcia-Albeniz, A.T. Chan. (2011) Aspirin for the prevention of colorectal cancer. Best Practice & Research Clinical Gastroenterology 25:4-5, 461-472
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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
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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
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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
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Timothy D. Warner, Sven Nylander, Carl Whatling. (2011) ANTI-PLATELET THERAPY: CYCLOOXYGENASE INHIBITION AND THE USE OF ASPIRIN WITH PARTICULAR REGARD TO DUAL ANTI-PLATELET THERAPY. British Journal of Clinical Pharmacologyno-no
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Maiko Furukawa, Mikiko Fujita, Akira Takinishi, Ryoichi Misaka, Hikaru Nagahara. (2011) Low-dose Aspirin Delays Gastric Healing after Helicobacter pylori Eradication. Internal Medicine 50:9, 951-959
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Mar Castellanos, Babette B. Weksler, Oscar R. Benavente. 2011. Antiplatelet Therapy for Secondary Prevention of Stroke. , 1147-1172.
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David M. Greer. (2010) Aspirin and Antiplatelet Agent Resistance. CNS Drugs 24:12, 1027-1040
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Peter M Rothwell, Michelle Wilson, Carl-Eric Elwin, Bo Norrving, Ale Algra, Charles P Warlow, Tom W Meade. (2010) Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. The Lancet 376:9754, 1741-1750
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Robert Benamouzig, Bernard Uzzan. (2010) Aspirin to prevent colorectal cancer: time to act?. The Lancet 376:9754, 1713-1714
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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
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Guillaume Cayla, Jean-Philippe Collet, Johanne Silvain, Gérard Thiefin, France Woimant, Gilles Montalescot. (2010) Prevalence and clinical impact of Upper Gastrointestinal Symptoms in subjects treated with Low Dose Aspirin: The UGLA survey. International Journal of Cardiology
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P. A. Ringleb, M.-G. Bousser, G. Ford, P. Bath, M. Brainin, V. Caso, Á. Cervera, A.l Chamorro, Charlotte Cordonnier, L. Csiba, A. Davalos, H.-C. Diener, J. Ferro, W. Hacke, M. Hennerici, M. Kaste, P. Langhorne, K. Lees, D. Leys, J. Lodder, H. S. Markus, J.-L. Mas, H. P. Mattle, K. Muir, B. Norrving, V. Obach, S. Paolucci, E. B. Ringelstein, P. D. Schellinger, J. Sivenius, V. Skvortsova, K. Stibrant Sunnerhagen, L. Thomassen, D. Toni, R.r von Kummer, N. Gunnar Wahlgren, M. F. Walker, J. Wardlaw. 2010. Ischaemic Stroke and Transient Ischaemic Attack. , 101-158.
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Neal S. Kleiman. (2010) Resistance or resistors? Has Ohm's law come to antiplatelet therapy?. American Heart Journal 159:5, 713-715
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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
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Peter M Rothwell, Sally C Howard, Eamon Dolan, Eoin O'Brien, Joanna E Dobson, Bjorn Dahlöf, Peter S Sever, Neil R Poulter. (2010) Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. The Lancet 375:9718, 895-905
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John GF Cleland. (2010) Long-term aspirin for coronary artery disease: are we being deceived by a biased presentation of the evidence?. Future Cardiology 6:2, 141-146
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A. Dragani, S. Pascale, A. Recchiuti, D. Mattoscio, S. Lattanzio, G. Petrucci, L. Mucci, E. Ferrante, A. Habib, F. O. Ranelletti, G. Ciabattoni, G. Davi, C. Patrono, B. Rocca. (2010) The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy. Blood 115:5, 1054-1061
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Reinhold W. Stockbrugger. (2010) Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond. Current Colorectal Cancer Reports 6:1, 44-47
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Andrea Brassard. (2009) Identification of patients at risk of ischemic events for long-term secondary prevention. Journal of the American Academy of Nurse Practitioners 21:12, 677-689
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Christian Weimar, Ralph Weber, Hans-Christoph Diener. (2009) Antithrombotic medication for stroke prevention. Expert Review of Cardiovascular Therapy 7:10, 1245-1254
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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
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Joshua A. Beckman. (2009) Antithrombotic therapies in cerebrovascular disease: What should we use as secondary prevention in patients with carotid artery disease?. Catheterization and Cardiovascular Interventions 74:S1, S12-S16
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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
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Gene R. Pesola. (2009) Emergent Aspirin Use in Cardiovascular Disease in the Emergency Department: Oral Dosing versus Rectal Suppositories. Academic Emergency Medicine 16:2, 162-164
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Jens Minnerup, Wolf-Rüdiger Schäbitz. (2009) Multifunctional actions of approved and candidate stroke drugs. Neurotherapeutics 6:1, 43-52
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H. P. Adams. (2009) Secondary Prevention of Atherothrombotic Events After Ischemic Stroke. Mayo Clinic Proceedings 84:1, 43-51
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Peter D. Panagos. (2008) The approach to optimizing stroke care. The American Journal of Emergency Medicine 26:7, 808-816
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Elad I. Levy, J. Mocco, Rodney M. Samuelson, Robert D. Ecker, Babak S. Jahromi, L. Nelson Hopkins. (2008) Optimal Treatment of Carotid Artery Disease. Journal of the American College of Cardiology 51:10, 979-985
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Susan C. Fagan. (2008) Urgent Need for Secondary Stroke Prevention After Transient Ischemic Attack. The Consultant Pharmacist 23:2, 131-140
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Jesse Weinberger. 2008. Cerebrovascular Disease in the Elderly Patient. , 645-672.
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Robert A. Phillips. (2008) A Review of Therapeutic Strategies for Risk Reduction of Recurrent Stroke. Progress in Cardiovascular Diseases 50:4, 264-273
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Jesse Weinberger. (2008) Antiplatelet Agents for Stroke Prevention Following Transient Ischemic Attack. Southern Medical Journal 101:1, 70-78
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Zhao Zheng, Stefan Schwab, Armin Grau, Christian Berger. (2007) Neuroprotection by early and delayed treatment of acute stroke with high dose Aspirin. Brain Research 1186, 275-280
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Dan James Fintel. (2007) Antiplatelet Therapy in Cerebrovascular Disease: Implications of MATCH and CHARISMA Results for Cardiologists. Clinical Cardiology 30:12, 604-614
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Helmi L. Lutsep. (2007) New Developments in Secondary Stroke Prevention: Impact of the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) on Clinical Management. Journal of Stroke and Cerebrovascular Diseases 16:6, 263-267
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Dara G. Jamieson. (2007) Secondary Prevention of Ischemic Stroke: Evolution from a Stepwise to a Risk Stratification Approach to Care. Disease Management 10:5, 273-284
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Els LLM De Schryver, Ale Algra, Jan van Gijn, Ale Algra. 2007. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. .
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Graeme J. Hankey. (2007) Antiplatelet therapy for the prevention of recurrent stroke and other serious vascular events: a review of the clinical trial data and guidelines. Current Medical Research and Opinion 23:6, 1453-1462
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Mai N Nguyen-Huynh, S Claiborne Johnston. (2007) Evaluation and management of transient ischemic attack: an important component of stroke prevention. Nature Clinical Practice Cardiovascular Medicine 4:6, 310-318
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N. S. Anavekar, I. M. Tleyjeh, N. S. Anavekar, Z. Mirzoyev, J. M. Steckelberg, C. Haddad, M. H. Khandaker, W. R. Wilson, K. Chandrasekaran, L. M. Baddour. (2007) Impact of Prior Antiplatelet Therapy on Risk of Embolism in Infective Endocarditis. Clinical Infectious Diseases 44:9, 1180-1186
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Thomas Croft Buck, Lene Brandstrup, Ivan Brandslund, Jens Peter Kampmann. (2007) The effects of introducing a clinical pharmacist on orthopaedic wards in Denmark. Pharmacy World & Science 29:1, 12-18
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Jason Ellison, William Dager. (2007) Recent FDA Warning of the Concomitant Use of Aspirin and Ibuprofen and the Effects on Platelet Aggregation. Preventive Cardiology 10:2, 61-63
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Eric R. Bates, Joseph D. Babb, Donald E. Casey, Christopher U. Cates, Gary R. Duckwiler, Ted E. Feldman, William A. Gray, Kenneth Ouriel, Eric D. Peterson, Kenneth Rosenfield, John H. Rundback, Robert D. Safian, Michael A. Sloan, Christopher J. White, Robert A. Harrington, Jonathan Abrams, Jeffrey L. Anderson, Eric R. Bates, Mark J. Eisenberg, Cindy L. Grines, Mark A. Hlatky, Robert C. Lichtenberg, Jonathan R. Lindner, Gerald M. Pohost, Richard S. Schofield, Samuel J. Shubrooks, James H. Stein, Cynthia M. Tracy, Robert A. Vogel, Deborah J. Wesley. (2007) ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical Expert Consensus Document on Carotid Stenting. Journal of the American College of Cardiology 49:1, 126-170
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H.O. Ammar, M. Ghorab, S.A. El-Nahhas, R. Kamel. (2006) Design of a transdermal delivery system for aspirin as an antithrombotic drug. International Journal of Pharmaceutics 327:1-2, 81-88
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Naveed Akhtar, Dirk Deleu, Ashfaq Shuaib. (2006) Antithrombotic therapy in secondary stroke prevention. Aging Health 2:5, 787-797
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PAUL A. GURBEL, UDAYA S. TANTRY. (2006) Aspirin and Clopidogrel Resistance: Consideration and Management. Journal of Interventional Cardiology 19:5, 439-448
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L. LAINE. (2006) Review article: gastrointestinal bleeding with low-dose aspirin – what's the risk?. Alimentary Pharmacology and Therapeutics 24:6, 897-908
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PHA Halkes, J van Gijn, LJ Kappelle, PJ Koudstaal, A Algra. (2006) ESPRIT trial – Authors' reply. The Lancet 368:9534, 449
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Ale Algra, Els LLM De Schryver, Jan van Gijn, L Jaap Kappelle, Peter J Koudstaal, Ale Algra. 2006. Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin. .
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Matt Fisher, Volker Knappertz. (2006) The dose of aspirin for the prevention of cardiovascular and cerebrovascular events. Current Medical Research and Opinion 22:7, 1239-1248
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ELLM De Schryver, A Algra, J van Gijn, Ale Algra. 2006. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. .
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Jose Antonio Gonzalez-Correa, Jose Pedro De La Cruz. (2006) Triflusal: An Antiplatelet Drug with a Neuroprotective Effect?. Cardiovascular Drug Reviews 24:1, 11-24
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Hans-Christoph Diener. (2006) Secondary stroke prevention with antiplatelet drugs: have we reached the ceiling?. International Journal of Stroke 1:1, 4-8
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Nerses Sanossian, Bruce Ovbiagele. (2006) Multimodality Stroke Prevention. The Neurologist 12:1, 14-31
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Daniel F. Hogan. 2006. Prevention and Management of Thromboembolism. , 331-345.
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2006. Acetylsalicylic acid. , 15-29.
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Patrono, Carlo, García Rodríguez, Luis A., Landolfi, Raffaele, Baigent, Colin, . (2005) Low-Dose Aspirin for the Prevention of Atherothrombosis. New England Journal of Medicine 353:22, 2373-2383
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Matt Fisher, Volker Knappertz. (2005) Comments in Response to “Analysis of Risk of Bleeding Complications After Different Doses of Aspirin in 192,036 Patients Enrolled in 31 Randomized Controlled Trials”. The American Journal of Cardiology 96:10, 1467
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E. L. L. M. Schryver, J. Gijn, L. J. Kappelle, P. J. Koudstaal, A. Algra, . (2005) Non–adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke. Journal of Neurology 252:11, 1316-1321
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Christopher P. Cannon, Shamir R. Mehta, Sary F. Aranki. (2005) Balancing the Benefit and Risk of Oral Antiplatelet Agents in Coronary Artery Bypass Surgery. The Annals of Thoracic Surgery 80:2, 768-779
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Brian Clarke, Allan Moore, Ciaran Donegan. (2005) Management of transient ischemic attack: 2005. Expert Review of Cardiovascular Therapy 3:4, 591-599
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I van Wijk, LJ Kappelle, J van Gijn, PJ Koudstaal, CL Franke, M Vermeulen, JW Gorter, A Algra. (2005) Long-term survival and vascular event risk after transient ischaemic attack or minor ischaemic stroke: a cohort study. The Lancet 365:9477, 2098-2104
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Michael G. Miller, B. Daniel Lucas, Vasilios Papademetriou, Abdul-karim Elhabyan. (2005) Aspirin Under Fire: Aspirin Use in the Primary Prevention of Coronary Heart Disease. Pharmacotherapy 25:6, 847-861
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Rosemarie A Reiter, Bernd Jilma. (2005) Platelets and new antiplatelet drugs. Therapy 2:3, 465-502
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L. Pollak, A. Kessler, M. J. Rabey, B. Hartmann, Y. Goldhammer. (2005) Clinical characteristics of patients with ischemic ocular nerve palsies and lacunar brain infarcts: a retrospective comparative study. Acta Neurologica Scandinavica 111:5, 333-337
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S.H.A.J. Tytgat, D.M. Laman, A.M. Rijken, R. Klicks, A. Voorwinde, J.M. Ultee, H. Van Duijn. (2005) Emboli Rate During and Early after Carotid Endarterectomy after a Single Preoperative Dose of 120mg Acetylsalicylic Acid—A Prospective Double-Blind Placebo Controlled Randomised Trial. European Journal of Vascular and Endovascular Surgery 29:2, 156-161
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J. van Gijn, A. Algra. (2005) Anticoagulation in Ischemic Stroke: Opportunities in Arterial Disease. Cerebrovascular Diseases 20:2, 101-108
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Mai N. Nguyen-Huynh, S. Claiborne Johnston. (2005) Transient ischemic attack: A neurologic emergency. Current Neurology and Neuroscience Reports 5:1, 13-20
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ADNAN GIRAL, OSMAN OZDOGAN, CIGDEM A CELIKEL, NURDAN TOZUN, NEFISE B ULUSOY, CEM KALAYCI. (2004) Effect of Helicobacter pylori eradication on anti-thrombotic dose aspirin-induced gastroduodenal mucosal injury. Journal of Gastroenterology and Hepatology 19:7, 773-777
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Daniel F. Hogan, Michael P. Ward. (2004) Effect of clopidogrel on tissue-plasminogen activator-induced in vitro thrombolysis of feline whole blood thrombi. American Journal of Veterinary Research 65:6, 715-719
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Mitchell S. V. Elkind. (2004) Secondary stroke prevention: Review of clinical trials. Clinical Cardiology 27:S2, 25-35
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Michael Ezekowitz. (2004) Medical prevention of secondary stroke: A cardiologist's perspective. Clinical Cardiology 27:S2, 36-42
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Martin J Quinn, Herbert D Aronow, Robert M Califf, Deepak L Bhatt, Shelly Sapp, Neal S Kleiman, Robert A Harrington, David F Kong, David E Kandzari, Eric J Topol. (2004) Aspirin dose and six-month outcome after an acute coronary syndrome. Journal of the American College of Cardiology 43:6, 972-978
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Mitchell S. V. Elkind. (2004) The role of warfarin and aspirin in secondary prevention of stroke. Current Cardiology Reports 6:2, 135-142
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Christian Berger, Feng Xia, Wolf-Ruediger Schabitz, Stefan Schwab, Armin Grau. (2004) High-dose aspirin is neuroprotective in a rat focal ischemia model. Brain Research 998:2, 237-242
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Dejana R. Jovanovic, Ale Algra, Jan van Gijn. (2004) Classification of outcome events in the Dutch TIA trial: prognostic value of accepted and rejected events*. Current Medical Research and Opinion 20:3, 255-258
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Victor L. Serebruany, Alex I. Malinin, Roswith M. Eisert, David C. Sane. (2004) Risk of bleeding complications with antiplatelet agents: Meta-analysis of 338,191 patients enrolled in 50 randomized controlled trials. American Journal of Hematology 75:1, 40-47
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Babette B. Weksler. 2004. Antiplatelet Therapy for Secondary Prevention of Stroke. , 1107-1128.
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Cathie Sudlow, Charles P. Warlow. 2004. Long-Term Medical Management of Ischemic Stroke and Transient Ischemic Attack Due to Arterial Disease. , 1129-1150.
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S.C Howard, P.M Rothwell. (2003) Regression dilution of systolic and diastolic blood pressure in patients with established cerebrovascular disease. Journal of Clinical Epidemiology 56:11, 1084-1091
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S. Malhotra, Y. P. Sharma, A. Grover, S. Majumdar, S. M. Hanif, V. K. Bhargava, A Bhatnagar, P. Pandhi. (2003) Effect of different aspirin doses on platelet aggregation in patients with stable coronary artery disease. Internal Medicine Journal 33:8, 350-354
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(2003) Antiplatelet Therapy in Peripheral Arterial Disease. Consensus Statement. European Journal of Vascular and Endovascular Surgery 26:1, 1-16
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J van Gijn, A Algra. (2003) Aspirin and stroke prevention. Thrombosis Research 110:5-6, 349-353
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Robert G. Hart, Anne D. Leonard, Robert L. Talbert, Lesly A. Pearce, Elaine Cornell, Edwin Bovill, William M. Feinberg. (2003) Aspirin Dosage and Thromboxane Synthesis in Patients with Vascular Disease. Pharmacotherapy 23:5, 579-584
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Howard S. Kirshner. (2003) Medical Prevention of Stroke, 2003. Southern Medical Journal 96:4, 354-358
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Johnston, S. Claiborne, . (2002) Transient Ischemic Attack. New England Journal of Medicine 347:21, 1687-1692
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Hans-Christoph Diener, Peter Ringleb. (2002) Antithrombotic secondary prevention after stroke. Current Treatment Options in Cardiovascular Medicine 4:5, 429-440
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Paulette Mehta. (2002) Aspirin in the prophylaxis of coronary artery disease. Current Opinion in Cardiology 17:5, 552-558
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Andrea R. Redman, LaWanda C. Allen. (2002) Warfarin versus aspirin in the secondary prevention of stroke: The WARSS study. Current Atherosclerosis Reports 4:4, 312-318
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Birgitte H. Bendixen, Lenore Ocava. (2002) Evaluation and management of acute ischemic stroke. Current Cardiology Reports 4:2, 149-157
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Louis R. Caplan. (2002) Is the promise of randomized control trials ("evidence-based medicine") overstated?. Current Neurology and Neuroscience Reports 2:1, 1-8
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R. Donnelly, J.M.C. Yeung. (2002) Management of Intermittent Claudication: the Importance of Secondary Prevention. European Journal of Vascular and Endovascular Surgery 23:2, 100-107
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A Algra, ELLM De Schryver, J van Gijn, LJ Kappelle, PJ Koudstaal, Ale Algra. 2001. Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin. .
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Eric Graaff, Steven R. Steinhubl. (2001) Complications of oral antiplatelet medications. Current Cardiology Reports 3:5, 371-379
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Hans-Christoph Diener, Peter Ringleb. (2001) Antithrombotic secondary prevention after stroke. Current Treatment Options in Neurology 3:5, 451-462
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L. Creed Pettigrew. (2001) Antithrombotic Drugs for Secondary Stroke Prophylaxis. Pharmacotherapy: Official Journal of the American College of Clinical Pharmacy 21:4, 452-463
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Rafael Llinas, Louis R. Caplan. (2001) Evidence-based treatment of patients with ischemic cerebrovascular disease. Neurologic Clinics 19:1, 79-105
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W. Hacke, M. Kaste, T. Skyhoj Olsen, J.-M. Orgogozo, J. Bogousslavsky. (2000) European Stroke Initiative (EUSI) Recommendations for �Stroke Management�The European Stroke Initiative Writing Committee. European Journal of Neurology 7:6, 607-623
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Omar Aguejouf, Emmanuelle Malfatti, Philippe Belon, Christian Doutremepuich. (2000) Time Related Neutralization of Two Doses Acetyl Salicylic Acid. Thrombosis Research 100:4, 317-323
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Omar Aguejouf, Emmanuelle Malfatti, Philippe Belon, Christian Doutremepuich. (2000) Effects of Acetyl Salicylic Acid Therapy on an Experimental Thrombosis Induced by Laser Beam. Thrombosis Research 99:6, 595-602
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Colin T. McDonald, Walter J. Koroshetz. (2000) Transient ischemic attack and secondary stroke. Current Treatment Options in Neurology 2:4, 329-341
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(2000) Part 7: The Era of Reperfusion. Resuscitation 46:1-3, 239-252
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Hans-Christoph Diener. (2000) STROKE PREVENTION. Neurologic Clinics 18:2, 343-355
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S. Tanasescu, H. Lévesque, C. Thuillez. (2000) Pharmacologie de l'aspirine. La Revue de Médecine Interne 21, S18-S26
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I. Crassard, P. Niclot, M.G. Bousser. (2000) Aspirine et accidents ischémiques cérébraux. La Revue de Médecine Interne 21, S41-S49
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Bradford B. Worrall, Karen C. Johnston. (2000) Antiplatelet therapy in secondary stroke prevention. Current Atherosclerosis Reports 2:2, 104-109
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David Y. Graham, Naeem Moon. (1999) Low-dose aspirin may or may not damage the gastric mucosa. Gastroenterology 117:6, 1505
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Paolo Pozzilli, RDG Leslie. (1999) Aspirin and diabetes. Practical Diabetes International 16:8, 259-261
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H.C. Diener. (1999) Aspirin in the prevention of strokes. Biomedicine & Pharmacotherapy 53:7, 309-311
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Dammann, Burkhardt, Wolf. (1999) Enteric coating of aspirin significantly decreases gastroduodenal mucosal lesions. Alimentary Pharmacology and Therapeutics 13:8, 1109-1114
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Jan van Gijn. (1999) Low doses of aspirin in stroke pre vention. The Lancet 353:9171, 2172-2173
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Stéphane Andrieu, Marilyne Lebret, Jacques Maclouf, Fabrizio Bévérelli, Jean-François Giudicelli, Alain Berdeaux. (1999) Effects of Antiaggregant and Antiinflammatory Doses of Aspirin on Coronary Hemodynamics and Myocardial Reactive Hyperemia in Conscious Dogs. Journal of Cardiovascular Pharmacology 33:2, 264-272
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Agnita J. W. Boon, Joseph T. J. Tans, Ernst J. Delwel, Saskia M. Egeler-Peerdeman, Patrick W. Hanlo, Hans A. L. Wurzer, Jo Hermans. (1999) Dutch Normal-Pressure Hydrocephalus Study: the role of cerebrovascular disease. Journal of Neurosurgery 90:2, 221-226
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Petra C.G Simons, Michiel L Bots, Ale Algra, A.Stijn P van Teeffelen, Yolanda van der Graaf. (1998) Effect of timing of blood pressure measurement in the assessment of arterial stiffness: the SMART study. Ultrasound in Medicine & Biology 24:9, 1285-1289
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David C. Calverley, Gerald J. Roth. (1998) ANTIPLATELET THERAPY. Hematology/Oncology Clinics of North America 12:6, 1231-1249
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Carlo Patrono. (1998) Prevention of Myocardial Infarction and Stroke by Aspirin. Thrombosis Research 92:1, S7-S12
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M. Gajdos̆, V. Spustová, K. S̆ebeková, Z. Krivos̆íková, R. Dzúrik. (1998) Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage. Prostaglandins, Leukotrienes and Essential Fatty Acids 59:1, 17-21
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Emmanuelle Belougne-Malfatti, Omar Aguejouf, Françoise Doutremepuich, Philippe Belon, Christian Doutremepuich. (1998) Combination of Two Doses of Acetyl Salicylic Acid. Thrombosis Research 90:5, 215-221
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Edgar R. Gonzalez. (1998) Antiplatelet therapy in atherosclerotic cardiovascular disease. Clinical Therapeutics 20, B18-B41
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Mette Hurlen, Ingebjørg Seljeflot,. (1998) The Effect of Different Antithrombotic Regimens on Platelet Aggregation After Myocardial Infarction. Scandinavian Cardiovascular Journal 32:4, 233-237
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(1997) A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. Annals of Neurology 42:6, 857-865
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(1997) 9. Discussion. Journal of the Neurological Sciences 151, S53-S59
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(1997) 8. Safety. Journal of the Neurological Sciences 151, S41-S51
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(1997) 2. Study design and baseline data. Journal of the Neurological Sciences 151, S3-S5
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(1997) 6. Secondary endpoints. Journal of the Neurological Sciences 151, S27-S37
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(1997) 5. Primary endpoints. Journal of the Neurological Sciences 151, S13-S26
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