Less loop diuretic use in patients on sacubitril/valsartan undergoing remote pulmonary artery pressure monitoring

Abstract

Aims: Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF).

Methods and results: The MEMS-HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS-HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2 ] vs. non-users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2 , P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan-treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non-loop diuretics (P = 0.21).

Conclusions: In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes.

Trial registration: ClinicalTrials.gov NCT02693691.

Keywords: Drug therapy; Heart failure; Loop diuretics; Monitor; Pulmonary artery pressure.

Conflict of interest statement

M.B. reports personal fees from Abbott, Amgen, Astra‐Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Novartis, Servier, and Vifor. B.A. reports honoraria for Bayer and Novartis, and speaker fees from Abbott, Alnylam, Astra‐Zeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Vifor; served on the MEMS‐HF steering committee. F.W.A. has no conflicts of interest to report. J.B. reports honoraria for consultancy and speakers fees and scientific support by Abbott, Medtronic, and Biotronik and served on the MEMS‐HF steering committee. M.E.B. is an employee and shareholder of Abbott. J.J.B. was on the steering committee of the Abbott‐sponsored MONITOR‐HF study. G.E. reports personal fees from Astra‐Zeneca, Abbott, Boehringer Ingelheim, Novartis, and Vifor, all outside the submitted work. He further acknowledges non‐financial support from the University Hospital Würzburg, non‐financial support from Comprehensive Heart Failure Center Würzburg, and grant support from German Ministry for Education and Research (BMBF). L.H. has no conflicts of interest to report. A.W. is an employee and shareholder of Abbott. F.K. reports research funding by the German Federal Ministry of Economics and Technology, the European Commission, and the German Federal Ministry of Education and Research and served on the MEMS‐HF steering committee. S.R. reports honoraria for consultancy, speaker fees, and scientific support by Abbott and has received remuneration for lectures and/or consultancy from Actelion, Bayer, BMS, MSD, Novartis, Pfizer, Vifor, and United Therapeutics, and his institution has received research grants from Actelion, Bayer, Novartis, and United Therapeutics and served on the MEMS‐HF steering committee. S.D.A. reports receiving fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma and grant support from Abbott and Vifor Pharma. D.M.L. reports lecture fees and research grants from Abbott, Novartis, Vifor Pharma, Boehringer, Astra‐Zeneca, and Bayer. A.A. has no conflicts of interest to report. J.W. has received speaker honoraria from Bristol‐Myers Squibb. Q.Z. reports grants from Boehringer Ingelheim, personal fees from Astra‐Zeneca, grants and personal fees from Abbott, and personal fees from Novartis outside the submitted work. P.B.A. is an employee and stockholder of Abbott. C.E.A. reports grant support, personal fees, and/or non‐financial support from Abbott, Astra‐Zeneca, Boehringer Ingelheim, Medtronic, Novartis, ResMed, Thermo Fisher, and Vifor, all outside of the submitted work. She further acknowledges non‐financial support from the University Hospital Würzburg, non‐financial support from Comprehensive Heart Failure Center Würzburg, and grant support from German Ministry for Education and Research (BMBF).

© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1

Use of loop diuretic (A) and use of thiazide diuretic (B) over time in patients on sacubitril/valsartan (red) or no sacubitril/valsartan (black). P‐values denote comparison between individual time points and P‐values for a generalized linear model to compare diuretic utilization over time.

Figure 2

Change from baseline diuretic doses over time for loop diuretics (A) and thiazide diuretics (B) in patients with (dark red) and without (light red) sacubitril/valsartan.