Angiotensin Receptor Neprilysin Inhibition in Patients with Left Ventricular Assist Devices

Abstract

Angiotensin receptor neprilysin inhibitors (ARNI) are now an established therapy for HF pts. While LVADs are a life-prolonging treatment for advanced HF, optimal management of hypertension and HF in this population is not known. We sought to evaluate the safety and efficacy of ARNI therapy in LVAD pts. We retrospectively reviewed all LVAD pts implanted between 8/2010 and 5/2019 who were subsequently treated with ARNI for at least 3 months. The primary outcome was change in NT-proBNP between the time of ARNI initiation (t0) and at 3- and 6-mo follow up. Safety endpoints included changes in mean arterial blood pressure (MAP), serum creatinine and potassium pre- and post-ARNI therapy. Data on concomitant drug therapy including diuretic dosing equivalents were also gathered. The above mentioned variables were log-transformed prior to analysis with repeated measures ANOVA. Pairwise comparisons were performed with Bonferroni's post hoc test. 30 pts met our inclusion criteria (age 54.7 ± 15.5 y; 90% M; HM3 17[57%], HMII 12[40%], HVAD 1 [3%]). ARNI was initiated at a median of 250 [67 - 601] days after LVAD implant. Prior to ARNI initiation, 47% were on ACE inhibitor, 13% on ARB, 40% on neither and 60% were treated with diuretics, with an average oral furosemide equivalent dose of 34 mg/day. At t0, 73% were started on 24/26 mg, and at 6 mos, 27% were on 49/51 mg and 32% on 97/103 mg of ARNI (Table). There was no statistically significant change in median MAP, serum creatinine or potassium (Table). A significant decrease in NT-proBNP was noted from t0 to follow-up (t0 = 1082 pg/mL, 3 mos = 724 pg/mL, 6 mos = 651 pg/mL) (Figure). The use of ARNI therapy was well tolerated among LVAD pts. There was a significant decrease in NT-proBNP levels, an effect previously reported in HF pts without LVADs in the PARADIGM-HF and PIONEER-HF trials. Randomized studies to determine the role of ARNI on the clinical course of LVAD patients are warranted.