https://orcid.org/0000-0003-3297-9586
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ABSTRACT
Introduction: Sacubitril-valsartan is a recently approved drug. However, there are few data regarding safety issues. We aimed to summarize the available evidence regarding sacubitril-valsartan’s safety and tolerability.
Methods: We conducted a systematic review with meta-analysis of randomized controlled trials (RCTs) enrolling patients receiving sacubitril-valsartan for any condition, compared with standard therapy or placebo. Database search was performed in October 2019. Outcomes were adverse events (AEs), serious AEs (SAEs), discontinuation due to AEs, and five AEs of special interest. Data were reported using risk ratio (RR) and 95% confidence interval (95%CI).
Results: We included 20 RCTs (22510 participants). When compared with active controls, there were no differences in SAEs (RR=0.93, 95%CI 0.86–1.01) and AEs (RR=1.00, 95%CI 0.97–1.03). However, sacubitril-valsartan resulted in an 8% risk reduction in discontinuation due to AEs (95%CI 0.85–0.99) and an increased risk of hypotension (RR=1.45, 95%CI 1.27–1.67). The risk of angioedema was higher with follow-ups greater than 12 months (RR=2.36, 95%CI 1.29–4.33). There were no further significant differences in the remaining AEs' risk.
Conclusions: Sacubitril-valsartan was at least as safe and tolerable as active control, with a similar need of administration cautiousness, except for a higher risk of hypotension. However, one should consider the study’s limitations.
Article highlights
Sacubitril-valsartan’s safety was compared to standard therapy in 22510 patients.
Sacubitril-valsartan was at least as safe and tolerable as the standard therapy.
Despite similar safety profiles, sacubitril-valsartan had a higher risk of hypotension.
Angioedema is an unsettling adverse event related to sacubitril-valsartan.
Further studies should be performed with a focus on sacubitril-valsartan’s safety.
This box summarizes key points contained in the article.
Author contributions
D Caldeira, G Martins e Pereira and V Katerenchuk conceived the idea for the protocol and made the main contribution to planning and preparation of timelines for its completion. G Martins e Pereira and G S Duarte planned the data extraction and statistical analysis, as well as of risk of bias, quality of evidence and completeness of reporting assessments. G Martins e Pereira designed the tables and wrote the first draft of the manuscript, which was then reviewed and amended by C David, D Caldeira, F J Pinto, G S Duarte, J Costa, J J Ferreira, V Katerenchuk. All authors then approved the final written manuscript. D Caldeira is the guarantor for the work.
Declaration of interest
D Caldeira has participated in educational meetings and/or attended conferences or symposia (including travel, and/or accommodation) with Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis and Roche. F J Pinto received consultant and speaker fees from Astra Zeneca, Bayer, BMS, Boehringer Ingelheim and Daiichi Sankyo. J J Ferreira received consultant and speaker fees from Grunenthal, Fundação MSD (Portugal), TEVA, MSD, Medtronic, GlaxoSmithKline, Novartis, Lundbeck, Solvay, BIAL, Merck-Serono, Merz, Ipsen, Biogen, Acadia, Allergan, Abbvie and Sunovion-Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
Supplemental data for this article can be accessed here.