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Erschienen in: Cardiovascular Drugs and Therapy 5/2022

14.06.2021 | Original Article

Five Years of Sacubitril/Valsartan—a Safety Analysis of Randomized Clinical Trials and Real-World Pharmacovigilance

verfasst von: Yee Soo Kim, Simerjeet Brar, Natalie D’Albo, Amit Dey, Sachin Shah, Sarju Ganatra, Sourbha S. Dani

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 5/2022

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Abstract

Purpose

In PARADIGM-HF, sacubitril/valsartan showed a significant reduction in mortality and hospitalization for patients with heart failure with reduced ejection fraction. Despite proven efficacy, sacubitril/valsartan has moderate uptake in clinical practice. This study explores the safety profile of sacubitril/valsartan by comparing adverse events in RCT and real-world use.

Methods

We studied hypotension, renal dysfunction, hyperkalemia, and angioedema associated with sacubitril/valsartan in RCTs and pharmacovigilance databases. A random-effects meta-analysis was performed with six RCTs investigating sacubitril/valsartan vs. control/comparators in heart failure patients. WHO’s VigiBase, FAERS, and EMA’s EudraVigilance were mined to obtain spontaneously reported real-world adverse events. Disproportionality analysis was performed with the FDA’s OpenVigil 2.0.

Results

Six RCTs enrolled 15,538 patients with heart failure with reduced and preserved ejection fractions. There was no statistical difference for the composite of hypotension, renal dysfunction, hyperkalemia, and angioedema between sacubitril/valsartan and its comparators viz. ACEi or ARBs (OR 1.23, CI 0.98–1.56; p = 0.08). A total of 103,038 adverse events were registered in the spontaneous reporting systems. Hypotension was the most reported adverse event. Proportions of composite adverse events were 20% in VigiBase, 17% in FAERS, and 39% with EudraVigilance. Disproportionality analysis showed a lower risk of adverse events with sacubitril/valsartan than other guideline-directed heart failure medications used in clinical practice.

Conclusion

With increased uptake of sacubitril/valsartan, risks of hypotension, renal dysfunction, hyperkalemia, and angioedema appear low and acceptable in RCTs and global clinical practice.
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Metadaten
Titel
Five Years of Sacubitril/Valsartan—a Safety Analysis of Randomized Clinical Trials and Real-World Pharmacovigilance
verfasst von
Yee Soo Kim
Simerjeet Brar
Natalie D’Albo
Amit Dey
Sachin Shah
Sarju Ganatra
Sourbha S. Dani
Publikationsdatum
14.06.2021
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 5/2022
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07210-1

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