Dataset Information

Effect of Angiotensin-Neprilysin Versus Renin-Angiotensin System Inhibition on Renal Outcomes: A Systematic Review and Meta-Analysis.

ABSTRACT: Aims: We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in comparison with the renin-angiotensin-aldosterone system inhibitor (RAASi). Methods: Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. We pooled relative risks (RRs) with 95% confidence intervals (CIs) or the mean difference with 95% CIs for the variables. Results: Our search yielded 10 randomized controlled trials with a total of 18,362 patients. Compared with RAASi treatment, patients treated with sacubitril/valsartan had lower incidence of composite renal impairment (10 studies, 18,362 patients, RR 0.84; 95% CI 0.72-0.96, p = 0.01; I ² = 22%), ESRD development (3 studies, 13,609 patients, RR 0.53; 95% CI 0.30-0.96, p = 0.03; I ² = 0%), drug discontinuation due to renal events (4 studies, 9,995 patients, RR 0.58; 95% CI 0.40-0.83, p = 0.003; I ² = 47%), severe hyperkalemia (6 studies, 16,653 patients, RR 0.80; 95% CI 0.68-0.93, p = 0.01; I ² = 25%) and a slower eGFR decline (4 studies, 13,608 patients, WMD 0.56; 95% CI 0.36-0.76, p < 0.00001; I ² = 65%). Subgroup analysis demonstrated that sacubitril/valsartan was associated with a lower incidence of renal impairment in patients with heart failure and preserved ejection fraction (HFpEF), but not in those with heart failure and reduced ejection fraction (HFrEF). The superior renal function preservation of sacubitril/valsartan treatment was not associated with different baseline eGFR levels and follow-up duration. There was a smaller increase in the change in the urine albumin-to-creatinine ratio (UACR) (3 studies, 9,114 patients, SMD 0.06; 95% CI 0.02-0.10, p = 0.003; I ² = 14%) with sacubitril/valsartan treatment. However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF (p = 0.80 for interaction). Conclusion: Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.

SUBMITTER: Xu Y

PROVIDER: S-EPMC8640344 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundMedications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.Methods and findingsEligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints.ConclusionsIn adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment.Review registrationPROSPERO CRD42014014404.

Project description:BackgroundInhibitors of the renin angiotensin system and neprilysin (RAS-/NEP-inhibitors) proved to be extraordinarily beneficial in systolic heart failure. Furthermore, compelling evidence exists that impaired mitochondrial pathways are causatively involved in progressive left ventricular (LV) dysfunction. Consequently, we aimed to assess whether RAS-/NEP-inhibition can attenuate mitochondrial adaptations in experimental heart failure (HF).Methods and resultsBy progressive right ventricular pacing, distinct HF stages were induced in 15 rabbits, and 6 animals served as controls (CTRL). Six animals with manifest HF (CHF) were treated with the RAS-/NEP-inhibitor omapatrilat. Echocardiographic studies and invasive blood pressure measurements were undertaken during HF progression. Mitochondria were isolated from LV tissue, respectively, and further worked up for proteomic analysis using the SWATH technique. Enzymatic activities of citrate synthase and the electron transfer chain (ETC) complexes I, II, and IV were assessed. Ultrastructural analyses were performed by transmission electron microscopy. During progression to overt HF, intricate expression changes were mainly detected for proteins belonging to the tricarboxylic acid cycle, glucose and fat metabolism, and the ETC complexes, even though ETC complex I, II, or IV enzymatic activities were not significantly influenced. Treatment with a RAS-/NEP-inhibitor then reversed some maladaptive metabolic adaptations, positively influenced the decline of citrate synthase activity, and altered the composition of each respiratory chain complex, even though this was again not accompanied by altered ETC complex enzymatic activities. Finally, ultrastructural evidence pointed to a reduction of autophagolytic and degenerative processes with omapatrilat-treatment.ConclusionsThis study describes complex adaptations of the mitochondrial proteome in experimental tachycardia-induced heart failure and shows that a combined RAS-/NEP-inhibition can beneficially influence mitochondrial key pathways.

Project description:BackgroundChronic kidney disease (CKD) is defined by abnormalities in kidney structure and/or function present for more than 3 months. Worldwide, both the incidence and prevalence rates of CKD are increasing. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance through the kidney. RAAS activation is associated with hypertension, which is directly implicated in causation and progression of CKD. RAAS blockade, using drugs targeting individual RAAS mediators and receptors, has proven to be renoprotective.ObjectivesTo assess genomic variants present within RAAS genes, ACE, ACE2, AGT, AGTR1, AGTR2 and REN, for association with CKD.Design and data sourcesA systematic review and meta-analysis of observational research was performed to evaluate the RAAS gene polymorphisms in CKD using both PubMed and Web of Science databases with publication date between the inception of each database and 31 December 2018. Eligible articles included case-control studies of a defined kidney disease and included genotype counts.Eligibility criteriaAny paper was removed from the analysis if it was not written in English or Spanish, was a non-human study, was a paediatric study, was not a case-control study, did not have a renal disease phenotype, did not include data for the genes, was a gene expression-based study or had a pharmaceutical drug focus.ResultsA total of 3531 studies were identified, 114 of which met the inclusion criteria. Genetic variants reported in at least three independent publications for populations with the same ethnicity were determined and quantitative analyses performed. Three variants returned significant results in populations with different ethnicities at p<0.05: ACE insertion, AGT rs699-T allele and AGTR1 rs5186-A allele; each variant was associated with a reduced risk of CKD development.ConclusionsFurther biological pathway and functional analyses of the RAAS gene polymorphisms will help define how variation in components of the RAAS pathway contributes to CKD.

Dataset Information

Effect of Angiotensin-Neprilysin Versus Renin-Angiotensin System Inhibition on Renal Outcomes: A Systematic Review and Meta-Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets