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Effects of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with left ventricular systolic dysfunction: a meta-analysis of randomized controlled trials.

ABSTRACT: Sudden cardiac death (SCD) is an important cause of death in patients with left ventricular systolic dysfunction. Mineralocorticoid receptor antagonists (MRAs) may attenuate this risk. The objective of this meta-analysis was to assess the impact of MRAs on SCD in patients with left ventricular systolic dysfunction.We systematically searched PubMed, EMBASE, Cochrane, and other databases through March 30, 2012, without language restrictions. We included trials that enrolled patients with left ventricular ejection fraction of ?45%, randomized subjects to MRAs versus control and reported outcomes on SCD, total and cardiovascular mortality. Eight published trials that enrolled 11 875 patients met inclusion criteria. Of these, 6 reported data on SCD and cardiovascular mortality, and 7 reported data on total mortality. No heterogeneity was observed among the trials. Patients treated with MRAs had 23% lower odds of experiencing SCD compared with controls (odds ratio, 0.77; 95% confidence interval, 0.66-0.89; P=0.001). Similar reductions were observed in cardiovascular (0.75; 95% confidence interval, 0.68-0.84; P<0.001) and total mortality (odds ratio, 0.74; 95% confidence interval, 0.63-0.86; P<0.001). Although publication bias was observed, the results did not change after a trim and fill test, suggesting that the impact of this bias was likely insignificant.MRAs reduce the risk of SCD in patients with left ventricular systolic dysfunction. Comparative effectiveness studies of MRAs on SCD in usual care as well as studies evaluating the efficacy of other therapies to prevent SCD in patients receiving optimal MRA therapy are needed to guide clinical decision-making.

SUBMITTER: Bapoje SR

PROVIDER: S-EPMC3893922 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Effects of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with left ventricular systolic dysfunction: a meta-analysis of randomized controlled trials.

Bapoje Srinivas R SR Bahia Amit A Hokanson John E JE Peterson Pamela N PN Heidenreich Paul A PA Lindenfeld Joann J Allen Larry A LA Masoudi Frederick A FA

Circulation. Heart failure 20130212 2

<h4>Background</h4>Sudden cardiac death (SCD) is an important cause of death in patients with left ventricular systolic dysfunction. Mineralocorticoid receptor antagonists (MRAs) may attenuate this risk. The objective of this meta-analysis was to assess the impact of MRAs on SCD in patients with left ventricular systolic dysfunction.<h4>Methods and results</h4>We systematically searched PubMed, EMBASE, Cochrane, and other databases through March 30, 2012, without language restrictions. We includ ...[more]

PMID: 23403436

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Project description:BACKGROUND:Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) <35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70% to 80% of such patients have an LVEF >35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes. Therefore, those at high risk of SCD may gain longevity from successful implantable cardioverter defibrillator therapy. We investigated whether late gadolinium enhancement (LGE) cardiovascular magnetic resonance identified patients with dilated cardiomyopathy without severe LV systolic dysfunction at high risk of SCD. METHODS:We prospectively investigated the association between midwall LGE and the prespecified primary composite outcome of SCD or aborted SCD among consecutive referrals with dilated cardiomyopathy and an LVEF ?40% to our center between January 2000 and December 2011 who did not have a preexisting indication for implantable cardioverter defibrillator implantation. RESULTS:Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the prespecified end point, compared with 7 of 298 (2.3%) without (hazard ratio [HR], 9.2; 95% confidence interval [CI], 3.9-21.8; P<0.0001). Nine patients (8.9%) with LGE compared with 6 (2.0%) without (HR, 4.9; 95% CI, 1.8-13.5; P=0.002) died suddenly, whereas 10 patients (9.9%) with LGE compared with 1 patient (0.3%) without (HR, 34.8; 95% CI, 4.6-266.6; P<0.001) had aborted SCD. After adjustment, LGE predicted the composite end point (HR, 9.3; 95% CI, 3.9-22.3; P<0.0001), SCD (HR, 4.8; 95% CI, 1.7-13.8; P=0.003), and aborted SCD (HR, 35.9; 95% CI, 4.8-271.4; P<0.001). Estimated HRs for the primary end point for patients with an LGE extent of 0% to 2.5%, 2.5% to 5%, and >5% compared with those without LGE were 10.6 (95% CI, 3.9-29.4), 4.9 (95% CI, 1.3-18.9), and 11.8 (95% CI, 4.3-32.3), respectively. CONCLUSIONS:Midwall LGE identifies a group of patients with dilated cardiomyopathy and an LVEF ?40% at increased risk of SCD and low risk of nonsudden death who may benefit from implantable cardioverter defibrillator implantation. CLINICAL TRIAL REGISTRATION:URL: http://clinicaltrials.gov. Unique identifier: NCT00930735.

Project description:The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death.Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay.A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2.596-35.825), P = 0.009, respectively].Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP.

Project description:BACKGROUND:There is heated debate about the benefits of using mineralocorticoid receptor antagonists (MRAs) in addition to standard therapy in patients admitted for myocardial infarction (MI) with or without left ventricular dysfunction (LVD). METHODS:Randomized controlled trials (RCTs) were scanned by a formal search of electronic databases (PubMed, EMBASE, Cochrane Library, Ovid, and clinical trials) from their inception to April 2018. A meta-analysis was conducted using Review Manager 5.3 to identify studies reporting the efficacy of MRAs use in post-MI patients with or without LVD. RESULTS:Thirteen RCTs involving 11,365 individuals were eligible for this study. MRAs treatment reduced all-cause mortality by 16%, cardiovascular death by 16%, and death from heart failure (HF) by 22% in post-MI patients. MRAs use reduced all-cause mortality by 13% and cardiovascular death by 15% in post-MI patients with LVD, but there was no significant difference in all-cause mortality and cardiovascular death in post-MI patients without LVD (relative ratios [RR] 0.83, 95% confidence interval [CI] 0.26-2.69, P = .76, I = 0%; RR 1.01, 95% CI 0.33-3.09, P = .99, I = 0%). In 6 RCTs involving post-MI patients, MRAs treatment had a significant effect on improving left ventricular ejection fraction (LVEF) (mean difference 3.33, 95% CI 0.91-5.75, P = .007, I = 94%). Patients treated with MRAs did not show a decrease in recurrent MI or repeat revascularization compared with patients treated without MRAs (RR 0.95, 95% CI [0.80-1.12], P = .54, I = 0%; RR 1.09, 95% CI [0.79-1.50], P = .61, I = 0%). However, MRAs treatment significantly increased the incidence of hyperkalemia compared with patients treated without MRAs (RR 2.05, 95% CI [1.60, 2.61], P < .00001, I = 49%). CONCLUSION:MRAs treatment reduced all-cause mortality, cardiovascular death, and death from HF in post-MI patients. MRAs treatment also demonstrated a significant improvement in LVEF. MRAs reduced cardiovascular death and all-cause mortality in patients with LVD. Eplerenone significantly reduced all-cause mortality and cardiovascular death in post-MI patients. However, MRAs failed to show any cardiovascular benefit in post-MI patients without LVD.

Project description:Background Guidelines recommend mineralocorticoid receptor antagonist (MRA) use in patients with left ventricular ejection fraction ≤40% following a myocardial infarction plus heart failure or diabetes mellitus, based on mortality benefit in the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial. The objective of this study was to evaluate the real-world utilization of MRAs for patients with ST-segment-elevation myocardial infarction (STEMI) with left ventricular dysfunction. Methods and Results The prospective, population-based, Vancouver Coastal Health Authority STEMI database was linked with local outpatient cardiology records from 2007 to 2018. EPHESUS criteria were used to define post-STEMI MRA eligibility (left ventricular ejection fraction ≤40% plus clinical heart failure or diabetes mellitus, and no dialysis-dependent renal dysfunction). The primary outcome was MRA prescription among eligible patients at discharge and the secondary outcome was MRA prescription within 3 months postdischarge. Of 2691 patients with STEMI, 317 (12%) were MRA eligible, and 70 (22%) eligible patients were prescribed an MRA at discharge. Among eligible patients with no MRA at discharge, 12/126 (9.5%) with documented postdischarge follow-up were prescribed an MRA within 3 months. In multivariable analysis, left ventricular ejection fraction (odds ratio [OR], 1.55 per 5% left ventricular ejection fraction decrease; 95% CI, 1.26-1.90) and calendar year (OR, 1.23 per year, 95% CI, 1.11-1.37) were associated with MRA prescription at discharge. Other prespecified variables were not associated with MRA prescription. Conclusions In this contemporary STEMI cohort, only 1 in 4 MRA-eligible patients were prescribed an MRA within 3 months following hospitalization despite high-quality evidence for use. Novel decision-support tools are required to optimize pharmacotherapy decisions during hospitalization and follow-up to target this gap in post-STEMI care.

Project description:BackgroundMaximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort.MethodsThe study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids).ResultsMLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk.ConclusionsIn children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Dataset Information

Effects of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with left ventricular systolic dysfunction: a meta-analysis of randomized controlled trials.

Publications

Effects of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with left ventricular systolic dysfunction: a meta-analysis of randomized controlled trials.

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