Sacubitril/valsartan in real‐life European patients with heart failure and reduced ejection fraction: a systematic review and meta‐analysis

Abstract

Abstract Aims We systematically reviewed the European real‐world evidence (RWE) about sacubitril‐valsartan for heart failure with reduced ejection fraction. Methods and results Twenty‐one articles, including 16 952 subjects, were identified until 31 October 2020. Taking as reference the PARADIGM‐HF cohort, few baseline characteristics were presented in >80% of these studies, most often with high heterogeneity. In random‐effects model meta‐analysis, age was higher (mean difference +3.84, 95% CI 1.92–5.76), ischaemic aetiology (OR 0.76, 95% CI 0.64–0.91), hypertension (OR 0.55, 95% CI 0.37–0.82), and diabetes (OR 0.77, 95% CI 0.64–0.92) were less common, and the use of mineralocorticoid receptor antagonists was more frequent (OR 3.54, 95% CI 2.27–5.53) in real‐life than in PARADIGM‐HF. Other clinical and medical features were presented in 19–76% of the selected publications and suggested more severe heart failure with reduced ejection fraction. Sacubitril‐valsartan was titrated to 97/103 mg b.i.d. in 35% (95% CI 23–47) and discontinued in 12.8% (95% CI 7.4–18.3) patients. When reported, the incidence of hyperkalaemia (six studies, no. 1076), all‐cause mortality (five studies, no. 684), and any hospitalization (three studies, no. 390) was 12 (95% CI 5–19)/100 person‐year, 8 (95% CI 4–12)/100 person‐year, and 24 (95% CI 5–42)/100 person‐year, respectively. Knowledge contribution, a metric measuring the proportion of RWE provided by each article based on the number of reported variables and the sample size, was 58.8% and 13.6% for the two biggest investigations (12 082 and 2037 patients), and <5% for all others (most with <100 subjects). Conclusions Limited‐quality RWE indicates that there are important differences between European patients prescribed sacubitril‐valsartan and the PARADIGM‐HF population, including the frequency of target dose achievement.

Keywords

• Sacubitril‐valsartan
• ARNI
• Heart failure
• Real‐word
• Real‐life