Response by Andreas et al to Letter Regarding Article, “Increased Thromboembolic Events With Dabigatran Compared With Vitamin K Antagonism in Left Ventricular Assist Device Patients: A Randomized Controlled Pilot Trial”

e thank Heinrich-Nols and Kreuzer for their valuable and very detailed response regarding the indication of dabigatran, its dosing regimen, and relevant considerations regarding monitoring of anticoagulation.We had to shorten our initial article significantly and were not able to address all points regarding dabigatran dosing and management. 1 The dose was chosen in 2010 according to the approved indication at that time, which was the primary prevention of venous thromboembolic events after elective hip or knee replacement.Dabigatran 75-and 110-mg hard capsules were therefore available on the market and used in this trial.The first study participant was included in 2013 when dabigatran was also approved for prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation.The RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy) indeed applied a higher dose in addition to 110 mg BID of dabigatran in patients with atrial fibrillation. 2We agree that knowledge of plasma concentrations might improve the assessment of the anticoagulant effect in patients treated with dabigatran.However, this pharmacokinetic analysis is not available in clinical routine.The study protocol was adapted prior to study initiation to improve patient safety.We excluded patients in the early postoperative period and included stable patients at least 1 month after pump implantation.Furthermore, a stringent visit schedule and assessment of thrombin clotting time was added and an interim outcome analysis was performed.We assessed the results of the RE-ALIGN trial (Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients After Heart Valve Replacement) in detail, as discussed in the article. 3However, antithrombotic treatment for mechanical heart valves cannot be compared with requirements of left ventricular assist devices, where platelet inhibition is simultaneously introduced.We would like to confirm that Boehringer Ingelheim Pharma GmbH and Co KG had no role in study conduct or interpretation of results.The medicine used for the study group in this open-label, parallel group trial was not purchased from Boehringer Ingelheim but provided free of charge to the hospital; the medicine is registered as Pradaxa on the market and did not require specific labeling for use in this trial.