Evaluation of Platelet Therapy Response in Left Ventricular Assist Device Patients

Left Ventricular Assist Device (LVAD) therapy has become a well-established treatment option for end stage heart-failure either as a bridge to transplant or destination therapy. As previously reported, mechanical circulatory support (MCS) has continued to improve patient survival and quality of life due to improvements in device design as well as implantation technique.

However, HRAEs such as stroke, bleeding, and thrombosis, which are consequences of adverse interactions between the pump and circulating blood elements, are associated with the use of LVADs. Despite excellent clinical outcomes of continuous flow LVADs with one-year survival of 83%, the balance of pump thrombosis (PT) and bleeding continues to present a major treatment challenge. Recent reports indicate, that only 80% of the patients supported with the HeartMate 3 (Abbott Inc.) LVAD had a one-year freedom from gastrointestinal bleeding, and freedom from any neurological adverse event. PT is described in up to 8 % of the HeartWare HVAD (Medtronic Inc.) patients and in 1.4% of HeartMate 3 patients.

Therefore, during long-term treatment, oral anticoagulation with vitamin K antagonists (VKA), such as warfarin or phenprocoumon, is essential to reduce HRAEs in LVAD patients. Most recent guidelines of the International Society for Heart and Lung Transplantation (ISHLT) recommend for centrifugal rotary blood pumps (such as the HeartMate 3 and HVAD) to start oral anticoagulation and antiplatelet therapy on post-operative day (POD) 2 or 3, after removal of the chest tubes and an intended target INR of 2.0-3.0. Furthermore, the ISHLT guidelines recommend 81 - 325 mg daily antiplatelet therapy with ASA in addition to warfarin to decrease thrombotic risk. Specifically for HeartMate 3 patients, the manufacturer recommends 81 - 100mg ASA daily therapy which should start 2 or 3 days after implantation. The manufacturer recommended long term oral anticoagulation regimen for the HVAD pump is a combination of warfarin and ASA. In general, ASA should be started at a doses >81mg per day (e.g. moderate-dose ASA of 162mg or high-dose of 325mg per day) within 24 hours after implant if there are no postoperative bleeding complications.

The relevance of these ASA daily dose recommendations for LVAD patients are supported by the results of several recent clinical studies: Najjar et al. identified an ASA daily dose ≤ 81 mg as independent risk factor for HVAD PT; in addition, Teuteberg et al. also identified daily ASA doses ≤ 81 mg as significant risk factor for ischemic and hemorrhagic cerebrovascular accidents. Uriel et al. analyzed HRAEs at 6 months in the Momentum 3 trial (comparing HeartMate II and 3) with antithrombotic management including anticoagulation with warfarin and ASA therapy (81-325 mg daily). Absence of ASA at 30 days was independently associated with development of HRAE or death at 6 months after implantation. Based on these recommendations and recent publications, current best practice at the Medical University of Vienna includes oral anticoagulation with phenprocoumon (INR target of 2.0-2.5) and without contraindication, on POD 3, the antiplatelet therapy with ASA is initiated. ASA daily standard doses vary device-specific from 100 mg (HeartMate 3) to 200 mg (HVAD).

In addition, the optimal antithrombotic regimen remains uncertain, and the frequency of antiplatelet therapy monitoring differs among clinicians.