Implications of Renin-Angiotensin-System Blocker Discontinuation in Advanced Decompensated Heart Failure

Abstract

Introduction: The impact of renin-angiotensin-system blocker (RASB) use, or lack of, on renal function, blood pressure, and clinical outcomes during treatment for acute decompensated heart failure (ADHF) needs further clarification. Hypothesis: In comparison to patients with RASB use, discontinuing or non-use of a RASB will associate with worsening renal function, hypotension, and adverse long-term outcomes. Methods: Participants with an LVEF ≤ 40% in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization (ESCAPE) trial were included. Mixed effects models compared RASB use on serial serum creatinine and systolic blood pressure (SBP) measurements. Cox-proportional hazard models tested the association between RASB use and outcomes adjusted for age, male sex, potassium, SBP < 140 mmHg and baseline creatinine. Outcomes were validated in an independent ADHF cohort admitted to the Cleveland Clinic (n = 253). Results: Patients in the ESCAPE cohort (N = 402, age 56 ± 14 y, 74% male, 49% ischemic, LVEF 19 ± 6 %, and creatinine 1.5 ± 0.6 mg/dL) were separated into 4 groups based on RASB use at baseline and discharge: continued (n = 316), discontinued (n = 21), initiated (n = 42), and non-use (n = 23). RASB discontinuation or non-use was associated with higher serial serum creatinine levels than RASB continuation or initiation (P < .001 for both) but not with SBP measurements (P > .3 for both). In comparison to RASB continuation, RASB discontinuation and non-use was associated with ~75% increased risk of a 180-day composite of death, transplant, or re-hospitalization (HR 1.87, 95% CI 1.09–3.20, P = .02 and HR 1.72 1.04–2.82, P = .03, respectively, Figure A). Similarly in the validation cohort, RASB discontinuation and non-use versus RASB continuation were associated with ~65% and ~75% risk for 180-day death, transplant, LVAD, or re-hospitalization (HR 1.85, 95% CI 1.02–3.34, P = .04 and HR 95% CI 1.64, 95% CI 1.03–2.5, P = .04, respectively, Figure B). Conclusions: In comparison to RASB continuation, RASB discontinuation and non-use was associated with higher baseline and serial serum creatinine levels during treatment for ADHF, but not with changes in SBP. Furthermore, RASB discontinuation and non-use in ADHF were associated with an increased risk of adverse clinical outcomes. Given the persistent elevation of serum creatinine and unchanged blood pressures these findings question the practice of withholding RASB in the setting of renal insufficiency and marginal blood pressure in ADHF.