Background: Aspirin is the standard treatment for secondary prevention of stroke and other vascular events. Several studies suggest that triflusal may have a better safety profile. Objectives: To determine in people at high risk of vascular events whether triflusal is an effective and safe treatment for primary and secondary prevention of serious vascular events. Search methods: We searched the trials registers of the following Cochrane Review Groups: Stroke Group (last searched October 2004), Heart Group, Peripheral Vascular Diseases Group and Metabolic and Endocrine Disorders Group (last searched May 2003). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2003), MEDLINE (1977 to 2003) and EMBASE (1980 to 2003). We searched reference lists and contacted researchers in the field, authors of relevant trials and the drug manufacturer. Selection criteria: Randomised and quasi-randomised studies comparing triflusal with placebo or aspirin in people at high risk of vascular events. Data collection and analysis: Two authors independently assessed trial quality and extracted data. The primary outcome was a serious vascular event (non-fatal acute myocardial infarction (AMI), non-fatal ischemic or hemorrhagic stroke, or vascular death). Other efficacy and safety measures collected were frequency of different vascular events, adverse events, minor and major hemorrhages. Main results: (1) Aspirin versus triflusal: five studies enrolled patients with stroke or transient ischemic attack (TIA) (4 trials; 2944 patients; followed for 6 to 47 months) or AMI (one trial; 2275 patients; followed for 35 days). Entry criteria were similar within each subgroup of patients. Patient groups were appropriately selected and well matched. The primary outcome in all trials was a composite outcome of vascular events. Trials had no important bias except in one study (217 patients). For the primary outcome of a serious vascular event there was no significant difference between triflusal and aspirin; the odds ratio (OR) was 1.04 (95% confidence interval (CI) 0.87 to 1.23). Significant differences were found for frequency of hemorrhages, both minor (OR 1.60, 95% CI 1.31 to 1.95) and major (OR 2.34, 95% CI 1.58 to 3.46) and for non-hemorrhagic gastrointestinal adverse events (OR 0.84, 95% CI 0.75 to 0.95). Sensitivity analysis of well versus poorly allocated trials showed no significant differences. (2) Triflusal versus placebo: two trials enrolled patients with unstable angina (281 patients) or peripheral arteriopathy (122 patients), who were followed for 6 months. Triflusal was associated with a reduction in serious vascular events (OR 2.29, 95% CI 1.01 to 5.19; OR greater than 1 favours triflusal) and with a higher frequency of adverse events (OR 1.68, 95% CI 1.00 to 2.80). Authors' conclusions: 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.

INTRODUCTION:

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.

OBJECTIVE:

We compare the long-term occurrence of hemorrhagic complications with low doses of AAS and high doses of triflusal.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

A multicenter, double-blind, placebo-controlled study was carried out to evaluate the effect of a new antiplatelet agent, triflusal (2-acetoxy-4-trifluoromethyl benzoic acid), in the prevention of nonfatal myocardial infarction and cardiac or vascular death (principal end-points) in patients with unstable angina. 281 patients were randomly assigned to triflusal (300 mg t.i.d.; n = 143) or placebo (n = 138). After 6 months of treatment, the incidence of nonfatal acute myocardial infarction was significantly lower in the triflusal than in the placebo group: 6 patients (4.2%) versus 17 (12.3%), p = 0.013. The low number of deaths (2/143 triflusal versus 0/138 placebo recipients) hampered statistical analysis of mortality rates. The need for revascularization was similar in the two groups: 24 patients (16.8%) in the triflusal group and 28 (20.3%) in the placebo group, p = 0.449. In conclusion, the results show that treatment with triflusal can reduce the incidence of myocardial infarction in patients with unstable angina.

OBJECTIVE:

To compare the costs to the Spanish healthcare system of 35 days' treatment with triflusal (600 mg/day) and aspirin (300 mg/day) in patients with confirmed acute myocardial infarction within 24 hours of onset of symptoms.

DESIGN:

A cost minimisation analysis based on the results of the Triflusal in Acute Myocardial Infarction study (TIM) was conducted. The hypothesis was that despite a higher acquisition cost of triflusal, savings would result because of differences in efficacy and safety outcome (non-fatal cerebrovascular event and haemorrhagic events). Diagnostic Related Groups were used as a proxy for determining hospital costs in Spain and the values were obtained from different sources and refer to year 2000 costs. Only direct medical costs were considered for the economic analysis.

RESULTS:

Although the acquisition cost of triflusal was more expensive than that of aspirin, the cost of prevented events - non-fatal ischaemic cerebrovascular events and cerebral haemorrhages - entirely compensated for the cost of triflusal. The overall cost of treating patients with triflusal, compared with aspirin, represented a net saving of 28.4% per patient treated.

CONCLUSION:

Our study showed that triflusal is cost saving compared with aspirin in the treatment of the acute phase of myocardial infarction.

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

AIMS:

To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction.

METHODS AND RESULTS:

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).

CONCLUSION:

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.

Many clinical trials have shown the effectiveness of platelet-antiaggregant drugs in the treatment of obliterative peripheral arteriopathy, both locally and in the system, by improving the claudication symptoms and by preventing major cardiovascular events. In this study we evaluated the effectiveness of a 24-week treatment with triflusal, a comparatively new inhibitor of platelet aggregation, in patients affected by chronic peripheral arteriopathy, comparing twice-daily oral doses of 300 mg triflusal with twice-daily placebo doses. The percentages of successes (defined as a 40% increase of total walking distance over the basal control) were 63.6% in the triflusal group (35/55 patients) and 22.5% in the placebo group (14/62 patients). Patients treated with triflusal showed a more important increase in total walking distance and in pain-free walking distance over the basal values than those treated with placebo, together with an improvement of the symptomatology correlated with claudication. Moreover, in the triflusal group there was an increase in the peak-flow recorded through strain-gauge plethysmography. In conclusion, triflusal significantly increased both the distance which could be walked and the clinical symptoms, presumably by improving microperfusion.

INTRODUCTION:

The effectiveness of the low doses AAS in the prevention of the cerebral infarction has not been clearly still verified.

OBJECTIVE:

To compare the long term effectiveness of the treatment with low doses AAS in front of triflusal in the reduction of the stroke, ischemic cardiopathy, and cardiovascular death risks.

MATERIAL AND METHODS:

Of 386 patients with a first ischemic stroke, 217 were selected (106 triflusal, 111 AAS) that completed the approaches of atheromatous infarct (161 males, 72.2% and 58 female, 25.8%). The mean age was 43 years (standard deviation, SD 6.4, 95% CL 20-50). The patients received one of theses treatments: a) AAS (Sedergine) 330 mg/day (once a day); b) Triflusal (Disgren), 900 mg/day (300 mg 3 times a day). The mean time of follow-up for the group triflusal was of 48.3 months (20-94), while for the group AAS was of 46.3 months (2-84).

RESULTS:

The combined incidence of cerebral infarcts, ischemic cardiopathy and vascular death was 19.8% in the patients treated with triflusal, and 28.8% in the patients treated with AAS what supposes a reduction of the risk of the 39% (OR 0.61; CL 0.30-2.01). In the subgroup of patients with carotid stenoses of more than 70% demonstrated by angiography, triflusal produces a significant reduction of risk (OR 0.30; CL 0.10-0.90). Also, triflusal reduced in 76% the risk of hemorrhagic complications in comparison of the AAS (OR 0.24; IC 0.06-0.94).

CONCLUSIONS:

The study adds new doubts about the effectiveness of the low doses of AAS in the secondary prevention of the cerebral infarct. The triflusal shows effectiveness in subgroup of high risk and a significative reduction of the hemorrhagic complications that would be confirmed in controlled clinical trials with a greater number of patients.

Triflusal is an antiplatelet agent structurally related to the salicylate group of compounds, but it is not derived from aspirin (acetylsalicylic acid). Platelet antiaggregant properties of triflusal and its active 3-hydroxy-4-trifluoro-methylbenzoic acid metabolite are primarily mediated by specific inhibition of platelet arachidonic acid metabolism. Triflusal, compared with placebo for 6 months, significantly reduced the incidence of nonfatal myocardial infarction in patients with unstable angina. In patients with peripheral arteriopathy, total and pain free walking distances were markedly improved in triflusal compared with placebo recipients. The cumulative event rate for stroke, ischemic cardiopathy and vascular death was lower, but not significantly different, in patients with atherothrombotic stroke who received triflusal than in aspirin recipients. Differences were significant, and favoured triflusal, in a subgroup of patients with > 70% carotid stenosis. Prophylaxis with triflusal for 6 months after aortocoronary vein grafting reduced the number of new distal anastomosis occlusions and the graft attrition rate more than aspirin or placebo. The incidence of deep vein thrombosis or pulmonary embolism in more than 500 patients undergoing hip surgery was similar for these 3 treatments. The amount of blood transfused was significantly reduced in triflusal compared with aspirin recipients who underwent hip surgery. Risk of haemorrhage was also reduced in ischemic stroke patients receiving triflusal versus aspirin.

BACKGROUND AND PURPOSE:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.