Lessons from the RE-ALIGN trial

Abstract

MOTS CLES Traitement anticoagulant ; Valvulopathies ; Protheses mecaniques Patients operated for mechanical heart valve replacement have a low rate of reintervention but suffer valve-related events due to thromboembolism and bleeding caused by anticoagulant therapy. New oral anticoagulants (NOACs) are easier to use than vitamin K antagonists and offer a good compromise between efficacy and safety in large trials on venous thromboembolism and non-valvular atrial fibrillation [1—5]. NOACs were therefore also promising in patients with mechanical heart valves. However, the presentation of the results of the Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement (RE-ALIGN) at the annual congress of the European Society of Cardiology in September 2013, followed by their publication, was disappointing [6]. The RE-ALIGN trial was a phase II trial in which the main endpoint was to validate a dose algorithm to obtain a trough level of dabigatran > 50 ng/mL. Thromboembolic events and bleeding, which are the usual clinical endpoints in studies on anticoagulant therapy for prosthetic heart valves, were secondary endpoints. The majority of patients (68%) had single aortic valve prosthesis, but only 29% were classified as at low risk for thromboembolism. Patients were randomized according to a 2:1 ratio to dabigatran or warfarin, either during the first week following valve replacement, or at least 3 months after surgery. Dabigatran doses in the RE-ALIGN trial were far higher than in atrial fibrillation or venous thromboembolism. The starting dose was between 150 and 300 mg twice daily according to creatinine clearance and was readjusted according to actual dabigatran plasma level. The lowest dose in the RE-ALIGN trial corresponded to the highest dose in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial [3]. It was used in only 15% of patients as a starting dose and 11% after readjustment. Thus, 89% of patients in the RE-ALIGN trial received a higher dose of dabigatran than in other indications.