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

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.