Triflusal vs aspirin for prevention of cerebral infarction: a randomized stroke study. Comparison of triflusal and aspirin for prevention of vascular events in patients after cerebral infarction: the TACIP Study: a randomized, double-blind, multicenter trial. Randomized comparative trial of triflusal and aspirin following acute myocardial infarction. "AICLA" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial.
Triflusal is an antiplatelet agent that has shown clinical advantages when compared with aspirin in the secondary prevention of vascular events. TAPIRSS (Triflusal versus Aspirin for Prevention of Infarction: a Randomized Stroke Study) explored the efficacy and safety of triflusal in the secondary prevention of stroke in a Latin American homogeneous population with the ultimate aim of preparing for a larger trial in the same setting.
                A double-blind, multicenter, randomized, pilot trial was conducted in Buenos Aires, Argentina, from October 1996 to November 1999. The study sample was 431 patients, randomized to receive aspirin 325 mg daily or triflusal 600 mg daily for a mean of 586 days. All patients had experienced either an ischemic stroke or TIA within 6 months from enrollment. Data from 429 patients were analyzed.
                No differences were observed in the primary endpoint that combined the incidence of vascular death, cerebral ischemic infarction, nonfatal myocardial infarction, or major hemorrhage (aspirin 13.9%, triflusal 12.7%; odds ratio [OR] 1.11, 95% CI 0.64 to 1.94) or in the individual analysis of each component of the primary endpoint. In a post hoc analysis, the overall incidence of major and minor hemorrhagic events was significantly lower in triflusal-treated patients (aspirin 8.3%, triflusal 2.8%; OR 3.13, 95% CI 1.22 to 8.06).
                This pilot trial has not found differences between triflusal and aspirin in the prevention of vascular complications after TIA or ischemic stroke, although given the wide CI, potentially important group differences could not be ruled out. Triflusal may be associated with a lower risk of hemorrhagic complications. A larger, prospective clinical trial is necessary to verify these results. The efficacy of the antiplatelet agent triflusal for prevention of vascular events after stroke has been reported in a pilot study. However, there is a need to confirm those results in a larger study.
                We performed a randomized, double-blind, multicenter study to test the efficacy of triflusal (600 mg/d) versus aspirin (325 mg/d) for prevention of vascular events in patients with stroke or transient ischemic attack (Triflusal versus Aspirin in Cerebral Infarction Prevention [TACIP]). We assessed a combined end point (incidence of nonfatal ischemic stroke, nonfatal acute myocardial infarction, or vascular death) as well as the incidence of these events separately and the incidence of major hemorrhage.
                Of 2113 patients, 1058 received triflusal and 1055 aspirin. The mean follow-up period was 30.1 months. The incidence of combined end point (13.1% for triflusal, 12.4% for aspirin) as well the survival analysis (hazard ratio [HR] for triflusal versus aspirin, 1.09; 95% CI, 0.85 to 1.38) showed no differences between groups. The incidence of nonfatal stroke (HR, 1.09; 95% CI, 0.82 to 1.44), nonfatal acute myocardial infarction (HR, 0.95; 95% CI, 0.46 to 1.98,) and vascular death (HR, 1.22; 95% CI, 0.75 to 1.96) was also similar. A significantly higher incidence of major hemorrhages in the aspirin group was recorded (HR, 0.48; 95% CI, 0.28 to 0.82). The overall incidence of hemorrhage was significantly lower in the triflusal group (16.7% versus 25.2%) (odds ratio, 0.76; 95% CI, 0.67 to 0.86; P<0.001).
                This study failed to show significantly superior efficacy of triflusal over aspirin in the long-term prevention of vascular events after stroke, but triflusal was associated with a significantly lower rate of hemorrhagic complications. To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction.
                In this double-blind, multicentre, sequential design study, patients were randomized within 24 h of acute myocardial infarction symptom onset to receive triflusal 600 mg or aspirin 300 mg once daily for 35 days. The primary end-point was death, non-fatal myocardial reinfarction or a non-fatal cerebrovascular event. The incidences of these individual outcomes and urgent revascularization were secondary end-points. The null hypothesis of no difference between treatments in the primary combined end-point was accepted with 80% power after recruiting 2124 validated patients (odds ratio (OR) for failure [95% confidence interval (CI)]: 0.882 [0.634-1.227]). Non-fatal cerebrovascular events were significantly less frequent with triflusal (OR [95% CI]: 0.364 [0.146-0.908]; P = 0.030). There was no significant difference between treatments for death (OR [95% CI]: 0.816 [0.564-1.179]; P = 0.278), non-fatal reinfarction (OR [95% CI]: 1.577 [0.873-2.848]; P = 0.131) or revascularization (OR [95% CI]: 0.864 [0.644-1.161]; P = 0.334). Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0.27% vs. 0.97%; P = 0.033).
                Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile. Triflusal significantly reduced the incidence of non-fatal cerebrovascular events compared with aspirin.
                Copyright 2000 The European Society of Cardiology. 604 Patients with atherothrombotic cerebral ischemic events (transient, 16%: or completed, 84%) referrable either to the carotid or to the vertebral-basilar circulation were entered into a double blind randomized clinical trial (AICLA) to determine whether aspirin (A) (1 g/day) or aspirin (1 g/day) + Dipyridamole (225 mg/day) (AD) would produce a significant reduction in the subsequent (3 years) occurrence of fatal and nonfatal cerebral infarction. Randomization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study. Adherence to the protocol and drug compliance were excellent. Side effects, particularly symptoms of peptic ulcer and hemorrhagic events were significantly (p less than 0.03) more frequent in the two treatment groups containing aspirin. With the exception of patients who withdrew from the study, each patient was followed for 3 years. At the end of the study, the number of fatal and nonfatal cerebral infarctions was 31 in the placebo (P) group, 17 in the A group and 18 in the AD group. Taking into account the duration of follow-up for each patient, these figures correspond to cumulative rates of 18% in the P group and 10.5% in each of the 2 active treatment groups. Analysis with the Mantel Method showed: 1)--A difference at the 6% level between the 3 groups and between P and AD; 2)--A difference at the 5% level between P and A; 3)--No difference between (A and AD; 4)--A difference at the 2% level between the P group and the two treated groups taken together (A + AD). Among other diseases occurring during the trial, the only significant difference concerned myocardial infarction, which was less frequent in the 2 treated groups (P less than 0.05). Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin. It is concluded that, in patients comparable to those defined in the protocol, Aspirin (1 g) has a significantly beneficial effect in the secondary prevention of atherothrombotic cerebral infarction. Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of vascular events after ischaemic stroke of presumed arterial origin are inconsistent. Our aim was to resolve this uncertainty.
                We did a randomised controlled trial in which we assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin. Our primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070).
                Mean follow-up was 3.5 years (SD 2.0). Median aspirin dose was 75 mg in both treatment groups (range 30-325); extended-release dipyridamole was used by 83% (n=1131) of patients on the combination regimen. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs 184), mainly because of headache.
                The ESPRIT results, combined with the results of previous trials, provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin. Blacks are disproportionately affected by stroke, and they are about 2 times more likely than most other individuals in the United States to die of or experience stroke.
                To determine the efficacy and safety of aspirin and ticlopidine to prevent recurrent stroke in black patients.
                Randomized, double-blind, investigator-initiated, multicenter trial of 1809 black men and women who recently had a noncardioembolic ischemic stroke and who were recruited between December 1992 and October 2001 from 62 academic and community hospitals in the United States and followed up for up to 2 years.
                A total of 902 patients received 500 mg/d of ticlopidine and 907 received 650 mg/d of aspirin.
                Recurrent stroke, myocardial infarction, or vascular death was the composite primary end point (according to intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke.
                The blinded phase of the study was halted after about 6.5 years when futility analyses revealed a less than 1% probability of ticlopidine being shown superior to aspirin in the prevention of the primary outcome end point. The primary outcome of recurrent stroke, myocardial infarction, or vascular death was reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of 907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval, 0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not differ significantly (P =.12 by log-rank test). Kaplan-Meier curves for time to the secondary outcome of fatal or nonfatal stroke approached a statistically significant reduction favoring aspirin over ticlopidine (P =.08 by log-rank test). The frequency of laboratory-determined serious neutropenia was 3.4% for patients receiving ticlopdine vs 2.2% for patients receiving aspirin (P =.12) and 0.3% vs 0.2% for thrombocytopenia, respectively (P =.69). One ticlopidine-treated patient developed thrombocytopenia, which was thought to be a case of possible thrombotic thrombocytopenia purpura, and recovered after therapy with plasmapheresis.
                During a 2-year follow-up, we found no statistically significant difference between ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, or vascular death. However, there was a nonsignificant trend for reduction of fatal or nonfatal stroke among those in the aspirin group. Based on these data and the risk of serious adverse events with ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black patients with noncardioembolic ischemic stroke.
No significant differences were found between triflusal and aspirin for secondary prevention of serious vascular events in patients with stroke or TIA and AMI. However, our review cannot exclude moderate differences in efficacy. Triflusal was associated with a lower risk of hemorrhagic complications.