salicylates and Cerebral-Infarction

Triflusal (Aflen, Disgren, Tecnosal, Triflux) is a novel platelet antiaggregant with structural similarities to salicylates, but which is not derived from aspirin. It has similar efficacy to aspirin in patients with cerebral or myocardial infarction, but has a reduced risk of haemorrhagic complications. In addition, triflusal plus moderate-intensity anticoagulation has demonstrated efficacy when used as thromboprophylaxis in atrial fibrillation. As such, triflusal has a role in the primary prevention of cerebrovascular events in atrial fibrillation, and for the secondary prevention of cerebral and myocardial infarction, primarily as an alternative to aspirin in patients for whom aspirin is unsuitable.

Topics: Atrial Fibrillation; Cardiovascular Diseases; Cerebral Infarction; Drug Interactions; Humans; Meta-Analysis as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Salicylates; Thromboembolism

Different studies have shown that aspirin (AAS), in low doses, may lead to a considerable frequency of hemorrhagic complications when used in the long term.. We compare the long-term occurrence of hemorrhagic complications with low doses of AAS and high doses of triflusal.. Our series included 106 patients who took 900 mg triflusal per day (300 mg 3 times per day) and 111 who took AAS (330 mg/day once daily). The former were followed up for an average period of 48.3 months (20-94) and the latter for 46.3 months (2-84). The average follow-up period for the study was 47.3 months. The presence of hemorrhagic complications was evaluated, as was their frequency and follow-up curve.. Compared with AAS, triflusal led to a 76% reduction in risk of hemorrhagic complications (2.8% against 10.8%; OR 0.24; IC 0.06-0.94). There was a slightly increased incidence of hemorrhages in the women's group. There were more hemorrhages than gastrointestinal hemorrhages (4.5% against 0.9%) and intracranial hemorrhages (1.8%-0.9%). The follow-up curve showed significant differences in the form of an increased risk of hemorrhagic complications with AAS.. The risk of hemorrhage with AAS depended on the period of follow-up, in a similar manner to with oral anticoagulant agents, in patients with prophylaxis of cerebral infarct. On the other hand, this did not occur with triflusal, with which the risk was homogeneous and lower in the long term.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cerebral Infarction; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Salicylates; Sex Factors; Time Factors

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.

Topics: Aged; Aspirin; Cerebral Infarction; Double-Blind Method; Female; Follow-Up Studies; Humans; Ischemic Attack, Transient; Male; Middle Aged; Odds Ratio; Pilot Projects; Platelet Aggregation Inhibitors; Salicylates; Secondary Prevention; Stroke; Survival Analysis; Treatment Outcome

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.

Topics: Aspirin; Cardiovascular Diseases; Cerebral Infarction; Double-Blind Method; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Salicylates; Secondary Prevention; Stroke; Survival Analysis

Topics: Aspirin; Cerebral Infarction; Humans; Pilot Projects; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Salicylates; Stroke; Treatment Outcome

This follow-up study was designed to evaluate whether the use of aspirin either before or after aneurysm rupture affects the occurrence of delayed cerebral ischemia. Aspirin inhibits platelet function and thromboxane production and has been shown to reduce the risk of various cardiovascular and cerebrovascular ischemic diseases. Following admission, the patients in this study was interviewed regarding their use of aspirin and other medicines prior to and after hemorrhage, and their urine was screened qualitatively for salicylates. Patient outcome and the occurrence of hypodense lesions consistent with cerebral infarction on follow-up computerized tomography (CT) were studied prospectively up to 1 year after hemorrhage. Of 291 patients, 31 (11%) died because of the initial hemorrhage and 18 (6%) died due to rebleeding within 4 days after hemorrhage. Of the remaining 242 patients, 90 (37%) had delayed cerebral ischemia, which caused a permanent neurological deficit or death in 54 patients (22%). Of 195 patients undergoing follow-up CT, 85 (44%) had cerebral infarction that was not seen on the CT scan obtained on admission. Those who had salicylates in the urine on admission had a relative risk of 0.40 (95% confidence interval (CI), 0.15 to 1.10) of delayed ischemia with fixed deficit and a risk of 0.40 (95% CI, 0.18 to 0.93) of cerebral infarction compared with patients who did not have salicylates in their urine. This reduced risk of ischemic complications with aspirin use was restricted to those patients who used aspirin before hemorrhage, when the risk of ischemia was 0.21 (95% CI, 0.03 to 1.63) and the risk of infarct was 0.18 (95% CI, 0.04 to 0.84) compared with those who had not used aspirin. The reduced risk of cerebral infarction remained significant after adjustment for several potential confounding factors (adjusted risk 0.19; 95% CI, 0.04 to 0.89). These observations suggest that platelet function at the time of subarachnoid hemorrhage may be associated with delayed cerebral ischemia after aneurysm rupture.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Brain Ischemia; Cerebral Infarction; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Prospective Studies; Salicylates; Subarachnoid Hemorrhage; Time Factors; Tomography, X-Ray Computed

MCA occlusion in animals is a common model for experimental stroke. In previous studies we have shown that one of the factors, which influence evolution of an infarct is microthrombosis in the area of infarction and in the surrounding brain tissue. The present study was undertaken for assessment of the number of microthrombi and of the size of brain infarcting in rats treated with the antiaggregatory substance Triflusal. 7 groups of Sprague-Dawley rats, each group consisting of 6 animals, underwent transsphenoidal MCA occlusion. The animals received Triflusal in various amounts from day 2 till day 6. At day 7 animals were decapitated and the brains were fixed in formaldehyde. The brain was dissected at the level of the optic chiasm and embedded in paraffin. Fresh microthrombi were detected py PTAH (Phosphotungstic acid hematoxylin) staining. In each animal the hemisphere with the ischemic lesion as well as the contralateral hemisphere were examined. The area of both hemispheres was calculated by subtraction of the ventricle area from the total brain area of a section. Infarct was defined as the region of necrosis which was sharply demarcated from normal brain. The infarcted area was planimetrically measured to obtain a ratio of infarcted to normal brain. A correlation between the effect of Triflusal, number of microthrombi and size of the infarcted area could be demonstrated. The pathogenetic role of the microthrombi in the evolution of cerebral infarction as well as the effect of Triflusal in different dosages on the number of microthrombi could be clearly assessed by quantitative morphometry.

Topics: Animals; Brain; Brain Damage, Chronic; Capillaries; Cerebral Infarction; Dose-Response Relationship, Drug; Intracranial Embolism and Thrombosis; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Sprague-Dawley; Salicylates