Aims
A therapeutic standard has been established with evidence of long-term survival by use of a fully magnetically levitated HeartMate 3 (HM3) left ventricular assist device (LVAD) (Abbott Industries, Abbott Park, IL) in patients with advanced heart failure.1 Outcomes with this pump have shown low rates of hemocompatibility-related adverse events (pump thrombosis, stroke, nonsurgical bleeding), and it has been argued that the thrombo-resistance demonstrated with this pump may facilitate consideration of direct oral anticoagulants (DOACs) that inhibit Factor Xa, although studies in legacy LVADs such as the HeartWare HVAD (Medtronic, Minneapolis, MN) demonstrated an increase in thrombotic complications with the use of dabigatran.2
We conducted a safety and feasibility study, the Direct Oral Anticoagulant Therapy with the HeartMate 3 LVAD (DOT-HM3) and enrolled 45 patients with the HM3 LVAD > 3 months post-implant, free of a bleeding episode or stroke, who tolerated a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2–3. Primary trial outcomes were published.3 Patients were randomly allocated to either apixaban 5 mg twice daily (apixaban plus aspirin, n = 15 and apixaban alone, n = 16) or continued therapy with VKA (warfarin plus aspirin, n = 14) in an open-label trial. The primary endpoint was survival free of pump thrombosis, disabling stroke or major bleeding at 6 months. Patients who were listed as bridge-to-transplantation were allowed enrollment, and occurrence of heart transplantation was considered success, provided patients survived the procedure to discharge from the hospital. All patients reached 6 months unless they were withdrawn or underwent transplantation without occurrence of thromboembolism (pump thrombosis, stroke or arterial thromboembolism) in either arm. Sporadic cases of bleeding were observed in the VKA arm with apixaban and 100 mg aspirin. Aspirin was used because the ARIES-HM3 (Antiplatelet Removal and Hemocompatibility Events With the HeartMate 3 Pump) trial had not concluded.4
In this analysis of heart transplantations performed in the apixaban arm (with or without aspirin), we describe the perioperative protocol, use of blood products, vascular complications, use of temporary mechanical circulatory support, renal-replacement therapy, and duration of hospital stay. Descriptive statistics are provided with the use of medians (range minimum–maximum).
Methods and results
A total of 8 heart transplants from brain-death donors were performed in apixaban-treated patients (6 of whom were within the 6-month duration and 2 who were beyond that timeframe), and the recipients ages were 55.5 years (42–64); donor ages were 47.5 years (36–58), and duration of LVAD implant was 626.5 days (range 250–2499). Once a donor organ was identified, recipients were instructed to hold apixaban immediately with the intent to avoid such use for at least 24 hours prior to transplant surgery. Four-factor prothrombin complex concentrate (4F-PCC) was used in all 8 patients and in 7 of 8 patients transplanted, a cytokine adsorption system was employed in cardiopulmonary bypass (CPB). Reversal agents to apixaban were not used in any case. Only 1 patient in the warfarin (plus aspirin) arm underwent transplantation, and this patient had a particularly complex course but was discharged with normal allograft function at 60 days. This isolated case is insufficient to provide a comparison to apixaban-treated patients.
Clinical Outcomes
Individual characteristics of the apixaban-arm patients who underwent transplantation are shown in Table 1. Chest closure was delayed in 7 of 8 patients, with a median time of 43 hours (0–52). The total ischemic time was 98 minutes (64–130) in 6 of 8 organs recovered after cold storage, and CPB time was 166.5 minutes (140–289). Two patients developed vascular complications (a ruptured aorta and bleeding from an internal thoracic artery). In 4 patients, extracorporeal membrane oxygenation support was required temporarily to allow recovery of the allograft function (4, 6, 6, and 14 days of support), while 6 of 8 patients required short-term renal-replacement therapy for a median of 14.5 days (5–37). The median use of blood products included packed red blood cells of 10.5 units (7–29), fresh-frozen plasma 15.5 units (10–39), and platelets of 6 units (4–10). The hospital stay was 45.5 days (30–71), of which 16 days (6–40) were in an intensive care setting. No cases of thromboembolism were encountered. All patients were discharged from the hospital setting with preserved allograft function (left ventricular ejection fraction of > 0.55 and without right-heart failure requiring pharmacological support)
https://doi.org/10.1016/j.cardfail.2024.05.005
Published: 6 August 2024
