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.
Subject(s)
Aminobutyrates/adverse effects , Angiotensin Receptor Antagonists/adverse effects , Tetrazoles/adverse effects , Aminobutyrates/administration & dosage , Angioedema/chemically induced , Angioedema/epidemiology , Angiotensin Receptor Antagonists/administration & dosage , Biphenyl Compounds , Drug Combinations , Humans , Hypotension/chemically induced , Hypotension/epidemiology , Randomized Controlled Trials as Topic , Risk , Tetrazoles/administration & dosage , ValsartanABSTRACT
OBJECTIVE: To undertake a systematic review and meta-analysis to assess the satisfaction of patients receiving nonvitamin K anticoagulants (NOACs), compared with vitamin K antagonists (VKAs). METHODS: We searched CENTRAL, MEDLINE, Embase, and Clinicaltrials.gov for randomized controlled trials (RCTs) and observational studies. Two reviewers screened, extracted, and appraised data independently. We pooled data using a random-effects model. Outcome included treatment satisfaction, which was assessed by scores of Duke Anticoagulation Satisfaction Scale (DASS), Anticlot Treatment Scale (ACTS), Perception of Anticoagulant Treatment Questionnaire 2 (PACT-Q2), or Treatment Satisfaction Questionnaire for Medication version II (TSQM-VII) and their domains reported with 95% confidence intervals (95% CIs). We followed MOOSE and PRISMA guidelines. RESULTS: We included four RCTs and 16 observational studies, enrolling 18,684 participants overall. Compared with VKAs, treatment with NOACs improved the ACTS Burdens score by 4.21 points (95% CI: 2.99-5.43, I 2 = 95%, combined n = 6,180), and ACTS Benefits by 0.49 points (95% CI: 0.18-0.81, I 2 = 85%, combined n = 6,171). Switching from VKAs to NOACs improved the ACTS Burdens score by 5.33 points (95% CI: 3.53-7.14, combined n = 3,097). Compared with VKAs, treatment with NOACs improved the TSQM-VII Global Satisfaction score by 6.86 points (95% CI: 3.00-10.73, combined n = 5,535). CONCLUSION: In patients with nonvalvular atrial fibrillation or venous thromboembolism, NOAC treatment is associated with greater satisfaction compared with VKAs. The switch from VKAs to NOACs was associated with improved patients' satisfaction. These effects were largely due to a lower degree of treatment burden with NOAC treatment.