Key result
Real-world European HFrEF patients on sacubitril-valsartan are ~4 years older than the PARADIGM-HF trial population.
Why the study?
The authors systematically reviewed European real-world evidence regarding sacubitril-valsartan for heart failure with reduced ejection fraction.
How do the baseline characteristics and outcomes of European real-world patients prescribed sacubitril-valsartan for HFrEF compare to the PARADIGM-HF trial population?
Systematic Review (n=16,952)
How do the baseline characteristics and outcomes of European real-world patients prescribed sacubitril-valsartan for HFrEF compare to the PARADIGM-HF trial population?
Real-world European patients prescribed sacubitril-valsartan for HFrEF are older and have a more severe clinical profile than the PARADIGM-HF trial cohort, with only 35% achieving the target dose.
May warrant caution extrapolating PARADIGM-HF benefits to older European patients; challenges trial generalizability and supports targeted real-world research.
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.
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Giovinazzo et al. (2021) conducted a systematic review in Heart failure with reduced ejection fraction (HFrEF) (n=16,952). Sacubitril/valsartan vs. PARADIGM-HF cohort was evaluated on Age difference compared to PARADIGM-HF (MD +3.84, 95% CI 1.92-5.76, p=<0.001). European real-world patients prescribed sacubitril-valsartan for heart failure with reduced ejection fraction were significantly older (mean difference +3.84 years) and had different baseline characteristics compared to the PARADIGM-HF trial population.
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