Sex Influence on the Efficacy and Safety of Sacubitril/Valsartan.

BACKGROUND: Women are underrepresented in sacubitril/valsartan (SV) clinical trials. The aim of this study was to assess sex-specific differences in efficacy, tolerability, and safety of SV in real-world heart failure with reduced ejection fraction (HFrEF) patients. METHODS: A prospective registry in 10 centers including all patients who started SV during the last 6 months was analyzed in this study. RESULTS: A total of 427 patients were included, 126 (29.5%) were women. There were no substantial differences in HFrEF treatment before SV initiation, although fewer women than men carried an implantable cardioverter defibrillator (57 [45.2%] vs. 173 [58.1%], p = 0.02). SV starting dose was 24/26 mg b.i.d. in 206 patients (48.2%), 49/51 mg b.i.d. in 184 (43.1%), and 97/103 mg b.i.d. in 34 (8.2%), without relevant differences associated to sex. There were no losses during a mean follow-up of 7.0 ± 0.1 months. The proportion of patients who discontinued the drug (16 [12.7%] women vs. 33 [11.0%] men, p = 0.66) or presented SV-related adverse effects (31 [24.6%] women vs. 79 [26.5%] men, p = 0.72) was also similar in both sexes. However, female sex was an independent predictor of functional class improvement in the multivariate analysis (odds ratio 2.33, 95% confidence interval: 1.24-4.38, p = 0.04). CONCLUSIONS: SV in women with HFrEF has a similar tolerability as in men. Females seem to have a more frequent functional class improvement than males.

Sacubitril/Valsartan in Daily Clinical Practice: Data From a Prospective Registry.

Sacubitril/valsartan (SV) is a new therapy in heart failure with reduced ejection fraction. Our aim was to determine the efficacy and safety of this drug daily clinical practice. We performed a multicenter registry in 10 hospitals. All patients who started SV from October 2016 to March 2017 on an outpatient basis were included. A total of 427 patients started treatment with SV. Mean follow-up was 7.0 ± 0.1 months. Forty-nine patients (11.5%) discontinued SV, and 12 (2.8%) died. SV discontinuation was associated with higher cardiovascular (hazard ratio 13.22, 95% confidence interval, 6.71-15.73, P < 0.001) and all-cause mortality (hazard ratio 13.51, 95% confidence interval 3.22-56.13, P < 0.001). Symptomatic hypotension occurred in 71 patients (16.6%). Baseline N-terminal pro-B-type natriuretic peptide levels, functional class, and left ventricular ejection fraction improved at the end of follow-up in patients who continued with SV (all P values ≤0.001). This improvement was not significant in patients with SV discontinuation. SV has a good tolerability in patients from daily clinical practice. SV withdrawal in patients with heart failure and reduced ejection fraction was independently associated with increased all-cause mortality. Patients who continued with SV presented an improvement in functional class left ventricular ejection fraction and N-terminal pro-B-type natriuretic peptide levels.

Clinical Profile of a Nonselected Population Treated With Sacubitril/Valsartan Is Different From PARADIGM-HF Trial.

Our aim is to describe the characteristics of the patients receiving sacubitril/valsartan (SV) in daily clinical practice. This is a prospective registry in 10 hospitals including all patients who started SV in everyday clinical practice. From October 2016 to March 2017, 427 patients started treatment with SV. The mean age was 68.1 ± 12.4 years, and 30.5% were women (22.0% in PARADIGM-HF, P < 0.001). Comparing our cohort with patients included in PARADIGM-HF, baseline treatment was different, with a lower ratio of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (2.7 vs. 3.5, P < 0.001), and a higher proportion of patients with implantable cardioverter defibrillator (53.8% vs. 15%, P < 0.001), and cardiac resynchronization therapy (25.8% vs. 5%, P < 0.001). Treatment with mineralocorticoid receptor antagonists was more frequent (76.7% vs. 60.0%, P < 0.001), and the use of beta-blockers was similar (94.6% vs. 93.0%, P = 0.43). We observed more patients in functional class III-IV (30.4 vs. 24.8, P = 0.015), higher levels of Nt pro-BNP [3421 (904-4161) vs. 1631 (885-3154) pg/mL] and worse renal function (creatinine level 1.3 ± 0.7 vs. 1.1 ± 0.3 mg/dL, P < 0.001). In real life, patients receiving SV have a higher risk profile than in the pivotal trial, poorer functional class, higher levels of natriuretic peptides, and worse renal function.