Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (trac): prospective, randomized, co-operative trial.

OBJECTIVE: Antiplatelet agents are used for prevention of thromboembolism in surgical patients and in patients with chronic atrial fibrillation. Up to date, however, results of randomized studies comparing antiplatelet agents and oral anticoagulation have not been reported. The aim of this study was to compare the efficacy and safety of triflusal (an antiplatelet agent) versus acenocoumarol for primary prevention of thromboembolism in the early postoperative period after implantation of a bioprosthesis. METHODS: In this prospective, multicentric, randomized, open pilot trial, patients were assigned to treatment with triflusal (600mg/d) or acenocoumarol (target INR 2.0-3.0). Study medication was started 24-48h after valve replacement with a bioprosthesis, and continued for 3 months. Four follow-up visits were scheduled: baseline, and at 1, 3 and 6 months thereafter. The primary end-point was a composite of the rate of thromboembolism, severe hemorrhage and valve-related mortality. RESULTS: A total of 193 patients were included (97 received triflusal and 96 acenocoumarol), with a mean age of 72.5 years. Half were men. Aortic valve replacement was performed in 181 patients (93.8%), mitral valve replacement in 10 patients (5.2%) and double valve replacement in 2 (1.0%). Hospital mortality was 11 (5.7%). Primary outcome was recorded in 9 patients with triflusal (9.4%) and in 10 patients with acenocoumarol (11%). There were nine episodes (4.7%) of thromboembolism, six in the triflusal group and three in the acenocoumarol group, and three episodes of permanent neurological deficits, one in the triflusal group and two in the acenocoumarol group. Severe hemorrhage: nine episodes, six in the acenocoumarol group and three in the triflusal group. None of the observed differences in efficacy were statistically significant. Regarding safety, three patients in triflusal group reported at least one hemorrhage, compared to 10 in acenocoumarol group (P=0.048). CONCLUSIONS: There were no significant differences in efficacy between both groups, however, triflusal showed a significantly lower incidence of bleeding episodes.

Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (TRAC): rationale and design for a prospective, randomized, co-operative trial.

Antiplatelet agents are used for prevention of thromboembolism in surgical patients and in patients with chronic atrial fibrillation. However, up-to-date results of randomized studies comparing antiplatelet agents and oral anticoagulation have not been reported. The aim of this study is to compare the efficacy and safety profile of triflusal versus acenocoumarol for primary prevention of thromboembolism in the early postoperative period after implantation of a bioprosthesis. This is a prospective, multicentric, randomized, open, pilot trial in which four acute-care teaching hospitals participate. Patients will be randomly assigned to treatment with triflusal or acenocoumarol the day before valve replacement with a bioprosthesis. Primary outcome will be the combined endpoint of the rate of either thromboembolism or hemorrhage and valve-related mortality in each treatment group. Secondary outcomes will include the analysis of each of these rates separately together with permanent valve-related impairment according to the guidelines for reporting morbidity and mortality after cardiac valvular operations. A total of 200 patients will be recruited in a competitive manner (100 patients per arm) over an 18-month period. The study will be completed in 2 years. Treatment assigned will be open to investigators and patients because of the need of blood monitoring and dosage adjustment in oral anticoagulant therapy. In order to minimize the bias, randomization is centrally performed. The study medication will be given for 3 months being discontinued afterwards. Follow-up visits are scheduled at the time of patient's inclusion in the study and at 1, 3, and 6 months thereafter. Homogeneity of groups will be analyzed using the Student's t test, the Mann-Whitney U test, and the chi-square test, when appropriate. Rates of thromboembolism and hemorrhage will be calculated with the hazard function. In conclusion, antiplatelet treatment for patients undergoing valve replacement with a bioprosthesis is clinically relevant because of avoidance of inconveniences of oral anticoagulation (monthly blood testing, dosage adjustment) and decreased risk of bleeding. In case the results favor the use of antiplatelet drugs in these patients, this study will contribute to future development of strategies in the prevention of thromboembolism.

Clinical Comparison of Dexketoprofen Trometamol, Ketoprofen, and Placebo in Dental Pain.

The efficacy and tolerability of single doses of dexketoprofen trometamol12.5 mg, 25 mg, and 50 mg and ketoprofen 50 mg were compared in this double-blind, randomized, placebo-controlled study of 210 patients with moderate to severe pain after removal of one mandibular impacted third molar tooth. Pain intensity and pain relief were monitored for 6 h after administration of medication using visual analogue and verbal rating scales. All four active treatments were significantly more effective than placebo (P < 0.001). Dexketoprofen 25 mg and 50 mg produced an analgesic effect within 30 min of administration and their effect persisted for 6 h. Ketoprofen 50 mg produced a level of analgesia similar to those of the higher doses of dexketoprofen trometamol, but it had a slower onset. The 12.5-mg dose of dexketoprofen trometamol was significantly superior to placebo but produced a lower level and shorter duration of analgesia compared to the other active treatments. There were no significant differences between 25 and 50 mg of dexketoprofen trometamol in any measure of analgesic efficacy. No serious adverse events were observed and there were no significant differences in the incidence of adverse events among treatment groups. These results demonstrate that dexketoprofen trometamol 25 mg is at least as effective as the racemic ketoprofen 50 mg in the treatment of postsurgical dental pain. The more rapid onset of action compared to ketoprofen suggests that dexketoprofen trometamol is more appropriate for treatment of acute pain.