Increased Bleeding Risk with Phosphodiesterase-5 Inhibitors after Left Ventricular Assist-Device Implantation

Abstract

Purpose Phosphodiesterase-5 inhibitors (PDE5I) are frequently implemented after left ventricular assist device implantation (LVAD) to improve right heart hemodynamics. No prospective study has yet evaluated the net benefit of off-label long-term PDE5I on clinical outcomes and their potential risks. We aimed to evaluate the impact of PDE5I on bleeding risk as well as severity and type of bleeding according to The Bleeding Academic Research Consortium (BARC) classification after LVAD implantation. Methods We retrospectively reviewed the database of our heart failure unit to identify adult patients who received a durable LVAD at our institution from December 2010 through May 2019. Patients were included in the analysis if they were discharged on oral PDE5I after LVAD implantation. Patients were excluded if they had received biventricular assist-devices, in case of postoperative death during the index hospitalization, follow-up interruption or follow-up in an affiliated hospital. Major bleeding was defined as fatal bleeding, and/or symptomatic bleeding in a critical area or organ, and/or bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. All non-major bleedings were considered minor bleedings. Results The analytic cohort included 109 patients. Seventy-five patients (69%) received long-term PDE5I therapy and thirty-four (31%) did not receive PDE5I. At 12 months 19 (17%) patients experienced cumulatively 28 bleeding events (26 events in patients on PDE5I, 2 not on PDEI5) leading to 27 red blood cell transfusions (all in the PDE5I group). Patients on PDE5I had higher bleeding rates (23% vs. 6%, p = 0.03) and more bleeding events per patient (0.32 vs. 0.06, p = 0.03). Most events concerned major bleeding (24 events, 85.7%) and 50% non-gastrointestinal bleeding. BARC Type 2 had the highest incidence and was more frequent in the PDE5I group (19 vs 3%, p = 0.03). Hospitalizations for bleeding and their duration were numerically higher for PDE5I (0.28 vs 0.03 hospitalizations, p = 0.07 and 2.4 vs. 0.2 days, p = 0.07, respectively). Conclusion Long-term PDE5I treatment after LVAD increases the risk of bleeding at 12 months after LVAD implantation. The role of off-label PDE5I in LVAD patients remains unclear and should be further clarified in contemporary patient and device cohorts.