PMID- 33459086 OWN - NLM STAT- MEDLINE DCOM- 20210513 LR - 20211204 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 20 IP - 5 DP - 2021 May TI - Safety and tolerability of sacubitril-valsartan: a systematic review and meta-analysis. PG - 577-588 LID - 10.1080/14740338.2021.1877658 [doi] AB - 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. FAU - Martins E Pereira, Goncalo AU - Martins E Pereira G AUID- ORCID: 0000-0003-3297-9586 AD - Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. FAU - S Duarte, Goncalo AU - S Duarte G AD - Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Faculdade de Medicina, Centro de Estudos de Medicina Baseada na Evidencia, Universidade de Lisboa, Lisboa, Portugal. FAU - Katerenchuk, Vasyl AU - Katerenchuk V AD - Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. FAU - Costa, Joao AU - Costa J AD - Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Faculdade de Medicina, Centro de Estudos de Medicina Baseada na Evidencia, Universidade de Lisboa, Lisboa, Portugal. FAU - David, Claudio AU - David C AD - Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Servico de Cardiologia, Hospital Universitario de Santa Maria (CHULN), CAML, Centro Cardiovascular da Universidade de Lisboa - CCUL, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. FAU - Ferreira, Joaquim J AU - Ferreira JJ AUID- ORCID: 0000-0003-3950-5113 AD - Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - CNS-Campus Neurologico Senior, Torres Vedras, Portugal. FAU - Pinto, Fausto J AU - Pinto FJ AD - Servico de Cardiologia, Hospital Universitario de Santa Maria (CHULN), CAML, Centro Cardiovascular da Universidade de Lisboa - CCUL, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. FAU - Caldeira, Daniel AU - Caldeira D AUID- ORCID: 0000-0002-2520-5673 AD - Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. AD - Servico de Cardiologia, Hospital Universitario de Santa Maria (CHULN), CAML, Centro Cardiovascular da Universidade de Lisboa - CCUL, Faculdade de Medicina, Universidade de Lisboa. Avenida Professor Egas Moniz, Lisboa, Portugal. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20210127 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 0 (Aminobutyrates) RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Biphenyl Compounds) RN - 0 (Drug Combinations) RN - 0 (Tetrazoles) RN - 80M03YXJ7I (Valsartan) RN - WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination) SB - IM MH - Aminobutyrates/administration & dosage/*adverse effects MH - Angioedema/chemically induced/epidemiology MH - Angiotensin Receptor Antagonists/administration & dosage/*adverse effects MH - Biphenyl Compounds MH - Drug Combinations MH - Humans MH - Hypotension/chemically induced/epidemiology MH - Randomized Controlled Trials as Topic MH - Risk MH - Tetrazoles/administration & dosage/*adverse effects MH - Valsartan OTO - NOTNLM OT - adverse effects OT - angiotensin-converting enzyme inhibitor OT - angiotensin-receptor blocker OT - calcium channel blocker OT - meta-analysis OT - sacubitril OT - sacubitril-valsartan OT - safety EDAT- 2021/01/19 06:00 MHDA- 2021/05/14 06:00 CRDT- 2021/01/18 08:41 PHST- 2021/01/19 06:00 [pubmed] PHST- 2021/05/14 06:00 [medline] PHST- 2021/01/18 08:41 [entrez] AID - 10.1080/14740338.2021.1877658 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2021 May;20(5):577-588. doi: 10.1080/14740338.2021.1877658. Epub 2021 Jan 27.