Dataset Information

Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials.

ABSTRACT:

Aims

Sacubitril-valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril-valsartan in patients with HF are controversial. We performed a meta-analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril-valsartan, valsartan, and enalapril in patients with HF.

Methods and results

We conducted a systematic search using PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. Randomized controlled trials involving the use of sacubitril-valsartan in patients with HF were included. We assessed the pooled odds ratio (OR) of all-cause mortality, cardiovascular mortality, and hospitalization for HF in fixed-effects models and the pooled risk ratio (RR) of symptomatic hypotension, worsening renal function, and hyperkalaemia in fixed-effects models. Of the 315 identified records, six studies involving 14 959 patients were eligible for inclusion. Sacubitril-valsartan reduced the endpoints of all-cause mortality and cardiovascular mortality in patients with HF with reduced ejection fraction (HFrEF) in three trials with pooled ORs of 0.83 (P = 0.0006) and 0.78 (P < 0.0001), respectively. Regarding the composite outcome of hospitalization for HF in five trials, the pooled OR was 0.79 (P < 0.00001). Compared with enalapril or valsartan, sacubitril-valsartan was associated with a high risk of symptomatic hypotension (RR 1.47, P < 0.00001), low risk of worsening renal function (RR 0.81, P = 0.005), and low rate of serious hyperkalaemia (?6.0 mmol/L) (RR 0.76, P = 0.0007) in all six trials.

Conclusions

Compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, sacubitril-valsartan significantly decreased the risk of death from all causes or cardiovascular causes in HFrEF and hospitalization for HF in both patients with HFrEF and HF with preserved ejection fraction. Sacubitril-valsartan reduced the risk of renal dysfunction and serious hyperkalaemia but was associated with more symptomatic hypotension.

SUBMITTER: Zhang H

PROVIDER: S-EPMC7754944 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials.

Zhang Hongzhou H Huang Tieqiu T Shen Wen W Xu Xiuxiu X Yang Pingping P Zhu Dan D Fang Haiyang H Wan Hongbing H Wu Tao T Wu Yanqing Y Wu Qinghua Q

ESC heart failure 20200925 6

<h4>Aims</h4>Sacubitril-valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril-valsartan in patients with HF are controversial. We performed a meta-analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril-valsartan, valsartan, and enalapril in patients with HF.<h4>Methods and result ...[more]

PMID: 32977362

Similar Datasets

Project description:AimsSacubitril/valsartan has been demonstrated to have cardiovascular benefits in patients with chronic heart failure (CHF). We aimed to conduct a meta-analysis of its effects on life quality in patients with CHF, in comparison with the angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB).MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception through March 2022 for all relevant randomized controlled trials assessing the impact of sacubitril/valsartan and ACEI/ARB on health-related quality of life (HRQoL) in patients with CHF. Two reviewers independently conducted study selection, data extraction, and assessment of bias and quality of evidence. Review Manager 5.3 software was used for meta-analysis.ResultsWe included 10 clinical studies involving 10,426 patients with heart failure with reduced ejection fraction (HFrEF) and 7,689 patients with heart failure with preserved ejection fraction (HFpEF). Meta-analysis results showed that, in terms of the primary outcome, the sacubitril/valsartan group was superior than the ACEI/ARB group in improving HRQoL of HFrEF, and the difference was statistically significant (SMD 1.26; 95% CI: 0.14, 2.37; p = 0.03), while there was no significant difference between the two groups in HFpEF (SMD 0.37; 95% CI: -0.35, 1.09; p = 0.32). The effect of sacubitril/valsartan on the secondary outcome of the minimal important improvement rate of HRQoL in HFrEF was consistent with the primary outcome, while the effect in HFpEF was not clear. The descriptive analysis of individual studies indicated no significant difference in the improvement of 6-min walk distance between the two groups.ConclusionSacubitril/valsartan is beneficial to improve HRQoL outcome in patients with HFrEF with high quality of evidence. Compared with ACEI/ARB, sacubitril/valsartan was more effective. While in patients with HFpEF, this improvement was similar between the two groups.

Project description:BackgroundControversy has persisted over the clinical benefits of low-dose sacubitril/valsartan in patients with heart failure (HF).HypothesisLow-dose sacubitril/valsartan might also be effective and safe in HF patients.MethodsElectronic databases including PubMed, Ovid, and Cochrane Library were systematically retrieved from inception to August 5, 2021. Review manager 5.4 and Stata 15.1 were employed in this systematic review and meta-analysis. Key efficacy outcomes of interest included HF hospitalization, all-cause mortality, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with New York Heart Association (NYHA) functional class. The safety outcome was systolic blood pressure (SBP). The grading of recommendations assessment, development, and evaluation approach was conducted to evaluate the quality of evidence for each outcome.ResultsA total of 1269 studies were screened and 9 real-world studies met the inclusion criteria were included in the meta-analysis, with 1697 participants. Compared with low-dose sacubitril/valsartan, high-dose sacubitril/valsartan significantly reduced the risk of HF hospitalization (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61, p < .0001) and the risk of all-cause mortality (OR: 0.23, 95% CI: 0.11-0.47, p < .0001). However, there were no appreciable differences in improvements of NYHA (OR: 0.59, 95% CI: 0.15-2.35, p = .45), changes of LVEF (mean difference [MD]: 2.73%, 95% CI: -2.24% to 7.7%, p = .28), changes of NT-proBNP (MD: 43.09, 95% CI: -28.41 to 114.59, p = .24) and changes of SBP (MD: 3.01, 95% CI: -4.62 to 10.64, p = .44) between groups with low-dose and high-dose sacubitril/valsartan.ConclusionsCompared with high-dose sacubitril/valsartan, low-dose sacubitril/valsartan was associated with increased risks of HF hospitalization and all-cause mortality. However, no distinct between-group differences in improvements of NYHA, changes of LVEF, changes of NT-proBNP and changes of SBP were observed.

Project description:A worsening renal function is prevalent among patients with cardiovascular disease, especially heart failure (HF). Sacubitril/valsartan appears to prevent worsening of renal function and progression of chronic kidney disease (CKD) as compared with renin-angiotensin system (RAS) inhibitors alone in HF patients. It is unclear whether these advantages are present in HF patients only, or can be extended to other categories of patients, in which this drug was studied. We performed a systematic review and meta-analysis to assess the consistency of effect size regarding renal outcome across randomized controlled trials (RCTs) that compared sacubitril/valsartan with RAS inhibitors in patients with or without HF. We searched Medline (PubMed), Scopus, and Thomson Reuters Web of Science databases until June 2020. We took into account RCTs that compared sacubitril/valsartan with a RAS inhibitor and reported data regarding renal function. We used random-effects models to obtain summary odds ratio (OR) with 95% confidence interval (CI). We extracted hazard ratios for renal outcomes, glomerular filtration rate slopes or rates of renal adverse events. Sensitivity analyses were performed by moderator analysis and random-effects meta-regression. The search revealed 10 RCTs (published between 2012 and 2019) on 16 456 subjects. Sacubitril/valsartan resulted in a lower risk of renal dysfunction as compared with RAS inhibitors alone [k = 10; pooled OR = 0.70 (95% CI 0.57-0.85); P < 0.001], with a moderate inconsistency between studies [Q(9) = 15.18; P = 0.086; I2 = 40.73%]. A stronger association was found in studies including older patients (k = 10; β = -0.047730; P = 0.020) or HF patients with preserved ejection fraction [pooled OR = 0.53 (0.41-0.68) vs. 0.76 (0.57-1.01) for studies on HF patients with reduced ejection fraction; P for comparison = 0.065]. The effect size did not change with different comparators (angiotensin-converting enzyme inhibitors vs. angiotensin II type 1 receptor blockers, P = 0.279). No significant association was found when the analysis was restricted to studies on non-HF patients [k = 3; pooled OR = 0.86 (0.61-1.22); P = 0.403] and studies with high risk of bias [k = 3; pooled OR = 0.34 (0.08-1.44); P = 0.143]. Our findings support the role of sacubitril/valsartan on preservation of renal function, especially in older patients and HF patients with preserved ejection fraction. However, evidence is currently limited to HF patients, while the renal outcome of sacubitril/valsartan therapy outside the HF setting needs to be further investigated.

Project description:BackgroundThe angiotensin-receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to the angiotensin receptor blocker (ARB) valsartan in terms of reversing heart failure classification (NYHA classification), reducing N-terminal pro-brain natriuretic peptide (NT-proBNP) level and cardiovascular mortality in many studies. Yet, the efficacy of ARNI did not come from patients with acute myocardial infarction (AMI).MethodsWe searched databases for research published from inception to July 29, 2022, that reported cardiac reverse remodeling (CRR) or security indices. Two reviewers independently screened literature, extracted data, and assessed the risk of bias. Nine studies enrolling 1,369 patients were included to perform a meta-analysis. There were 716 patients in the ARNI group and 653 in the ARB group.ResultsARNI outperformed ARBs in terms of CRR indices, with striking changes in left ventricular ejection fraction (EF) (MD: 4.12%, 95%CI: 2.36, 5.88, P < 0.0001), diameter (MD: -3.40 mm, 95%CI: -4.30, -2.94, P < 0.00001, I 2 = 0%) and left atrial diameter (MD: -2.41 mm, 95%CI: -3.85, -0.97, P = 0.001, I 2 = 0%), other indices there showed no significant improvements. The incidences of major adverse cardiac events (RR: 0.47, 95%CI: 0.34-0.65, P < 0.00001, I 2 = 0%), the heart failure (RR: 0.37, 95%CI: 0.23-0.61, P < 0.0001, I 2 = 0%), readmission (RR: 0.54, 95%CI: 0.36-0.80, P = 0.003, I 2 = 29%) in the sacubitril/valsartan group were lower than the ARB group, while the incidences of cardiac death (RR: 0.56, 95%CI: 0.28, 1.09, P = 0.09), the myocardial infarction (RR: 0.83, 95% CI: 0.39, 1.77, P = 0.63), adverse side effects (RR: 1.67, 95% CI: 0.89, 3.13, P = 0.11) showed no difference.ConclusionThis research indicated that early initiation of sacubitril/valsartan in patients after AMI was superior to ARBs in reducing the risks of major adverse cardiac events, heart failure, readmission, and enhancing left ventricular EF, decreasing diameter, left atrial diameter. As for the other outcomes (the incidences of cardiac death, myocardial infarction, and adverse side effects), sacubitril/valsartan demonstrated no obvious advantage over ARBs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier [CRD42022307237].

Dataset Information

Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials.

Aims

Methods and results

Conclusions

Publications

Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials.

Similar Datasets

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