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

Abstract

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.