Abstract
BackgroundData regarding using angiotensin receptor-neprilysin inhibitor (ARNI) in patients with both heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (CKD) are limited.Methods and ResultsBetween January 2016 and December 2018, patients with HFrEF and advanced CKD (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m2) were identified from a multi-institutional database in Taiwan. Patients who had never been prescribed with an ARNI, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) were excluded. We used inverse probability of treatment weighting (IPTW) to balance baseline covariates, and compared outcomes between ARNI and ACEI/ARB users. There were 206 patients in the ARNI group and 833 patients in the ACEI/ARB group. After IPTW adjustment, the mean ages (65.1 vs. 66.6 years), male patients (68.3 vs. 67.9%), left ventricular ejection fraction (30.5 vs.31.2%), eGFR (20.9 vs. 20.3 mL/min/1.73 m2) were comparable in the ARNI and ACEI/ARB groups. Over 85% of the patients had beta-blockers prescriptions in both groups (86.2 vs. 85.5%). After IPTW adjustment, the mean follow-up durations were 7.3 months and 6.6 months in the ARNI and ACEI/ARB groups, respectively. ARNI and ACEI/ARB users had a comparable risk of the composite clinical event (all-cause mortality or heart failure hospitalization) (hazard ratio [HR], 1.31; 95% confidence interval (CI) 0.91–1.88) and progression to dialysis (HR 1.04; 95% CI 0.54–2.03). In subgroup analysis, dialysis patients who used ARNIs were associated with higher incidence of heart failure hospitalization (subdistribution HR, 1.97; 95% CI 1.36–2.85).ConclusionsCompared with ACEIs or ARBs, ARNIs were associated with comparable clinical and renal outcomes in patients with HFrEF and advanced CKD (eGFR ≤ 30 mL/min/1.73 m2). In short-term, HF hospitalization may occur more frequently among ARNI users, especially in patients on dialysis.
Highlights
Chronic kidney disease (CKD) is not uncommon in patients with heart failure with reduced ejection fraction (HFrEF), as they have similar upstream risk factors and interact to increase adverse events
Between January 2016 and December 2018, a total of 1,039 HFrEF patients with two consecutive records of estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 at baseline, who received an angiotensin receptor-neprilysin inhibitor (ARNI), Angiotensin converting enzyme inhibitor (ACEI), or angiotensin receptor blockers (ARBs), and had available follow-up information were eligible for analysis
The results suggested that renal function at baseline significantly modified the association between the use of ARNIs and the risk of clinical outcomes, especially on the composite outcome (P for interaction = 0.0498) and HF hospitalization (P for interaction = 0.026)
Summary
Chronic kidney disease (CKD) is not uncommon in patients with heart failure with reduced ejection fraction (HFrEF), as they have similar upstream risk factors and interact to increase adverse events. The number of patients with both advanced CKD (eGFR ≤ 30 mL/min/1.73 m2) and HFrEF is increasing globally with high morbidity and mortality, [3, 4] they have been systemically excluded from randomized trials of pharmacological therapies for HFrEF. Despite a lack of evidence, some cardiologists in Taiwan prescribed sacubitril/valsartan for patients with HFrEF and advanced CKD in an attempt to either improve symptoms, reduce HF hospitalization, or prolong survival. Data regarding using angiotensin receptor-neprilysin inhibitor (ARNI) in patients with both heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (CKD) are limited
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