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Current Problems in Cardiology May 2023Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and... (Review)
Review
Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting-enzyme inhibitors are the treatments of choice for worsening clinical symptoms. In early 2021, the FDA approved a new oral soluble guanylate cyclase stimulator, Vericiguat, for the treatment of chronic heart failure. To evaluate the efficacy and safety of this approved drug, we conducted a systematic review of the available randomized controlled trials (RCTs). A literature search was conducted using PubMed, The Cochrane Library, and Clinicaltrials.gov from inception to June 6, 2022, without any language restriction. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was checked using the Cochrane Risk-of-Bias tool. After a thorough literature search, 7 studies met our pre-defined criteria and were therefore included in this review. Our review suggests that vericiguat was better in preventing all causes of death, cardiovascular death, and hospitalizations due to heart failure irrespective of the atrial fibrillation status of the patients and was even beneficial for patients with NT-proBNP levels up to 8000 pg/ml. The safety of the vericiguat, according to our review, is not up to the standards, especially with a higher dosage of vericiguat. Despite all of this, vericiguat can be a breakthrough in the treatment of heart failure as it has great potential to improve the disease severity.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists; Heterocyclic Compounds, 2-Ring; Heart Failure; Stroke Volume
PubMed: 36623755
DOI: 10.1016/j.cpcardiol.2023.101586 -
Annals of Medicine and Surgery (2012) Oct 2023The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease.... (Review)
Review
BACKGROUND AND OBJECTIVES
The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels.
METHODS
After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (=8487 in the finerenone group; =6975 in the control group) were included.
RESULTS
Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)].
CONCLUSION
Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.
PubMed: 37811017
DOI: 10.1097/MS9.0000000000001180 -
Renal Failure 2016Cardiovascular disease is an important factor in the mortality and morbidity of patients with end-stage renal disease receiving hemodialysis. Although mineralocorticoid... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cardiovascular disease is an important factor in the mortality and morbidity of patients with end-stage renal disease receiving hemodialysis. Although mineralocorticoid receptor antagonists may have potential benefits on the cardiovascular system, their safety for patients on hemodialysis remains unclear, considering the differences between the results of already performed clinical trials.
METHODS
MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov and PubMed databases were searched for relevant clinical trials. The Cochrane Collaboration assessment tool was employed to evaluate the quality of the randomized controlled trials. Revman 5.3 was used to perform the meta-analysis.
RESULTS
Eleven studies (n=379) were included in the systematic review and five randomized controlled trials were included in the meta-analysis (n=248). Mineralocorticoid antagonists (MRAs) did not increase predialysis potassium levels significantly (0.11, 95% confidence interval -0.03 to 0.25, p = 0.11). However, the studies included in this review reported inconsistently with respect to effects of mineralocorticoid receptor antagonists on blood pressure, left ventricular ejection fraction and left ventricular hypertrophy, and quantitative analysis was not performed due to insufficient data. One trial showed that the mineralocorticoid receptor antagonists were associated with decreased carotid intima-media thickness and other articles concluded that mineralocorticoid receptor antagonists had no effect on aortic stiffness.
CONCLUSION
It is safe to use low dose mineralocorticoid receptor antagonists on patients receiving hemodialysis, at the end of each session of hemodialysis, and close monitoring of serum potassium levels and possible side effects is necessary. The cardiovascular actions still need to be explored and large scale RCTs are in progress.
Topics: Cardiovascular Diseases; Humans; Kidney Failure, Chronic; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Renal Dialysis
PubMed: 26905224
DOI: 10.3109/0886022X.2016.1149684 -
BMJ Clinical Evidence Feb 2010Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort... (Review)
Review
INTRODUCTION
Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments, and of drug and invasive treatments, for heart failure? What are the effects of angiotensin-converting enzyme inhibitors in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 85 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists; amiodarone; angiotensin-converting enzyme inhibitors; angiotensin II receptor blockers; anticoagulation; antiplatelet agents; beta-blockers; calcium channel blockers; cardiac resynchronisation therapy; digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors); exercise; hydralazine plus isosorbide dinitrate; implantable cardiac defibrillators; multidisciplinary interventions; non-amiodarone antiarrhythmic drugs; and positive inotropes (other than digoxin).
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 21718583
DOI: No ID Found -
Medicine Jul 2017Mineralocorticoid responsive hyponatremia of the elderly (MRHE) is an emerging concept of hyponatremia in aged people. Diagnosis of MRHE requires exclusion of syndrome... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mineralocorticoid responsive hyponatremia of the elderly (MRHE) is an emerging concept of hyponatremia in aged people. Diagnosis of MRHE requires exclusion of syndrome of inappropriate antidiuresis and adrenal dysfunction. Thus we aimed to evaluate the characteristics of all patients with suspected MRHE available for a review.
METHODS
We conducted a systematic review using MEDLINE and Google scholar. We included published case reports of adult patients diagnosed as MRHE, written by English and Japanese language. Serum and urine electrolytes as well as the levels of antidiuretic hormone (ADH), cortisol, plasma renin activity (PRA), and aldosterone were analyzed.
RESULTS
A total of 27 MRHE patients were identified in 9 reports. In these patients, average age was 79 years, median serum sodium was 117 mEq/L. The median levels of ADH, cortisol, PRA, and aldosterone were 0.9 pg/mL, 18.7 μg/dL, 0.37 ng/mL/h, and 39.6 pg/mL, respectively. Water restriction test was conducted in 7 patients. Random sample cortisol measurements did not exceed satisfactory levels to rule out adrenal dysfunction in four cases. No cases underwent low-dose adrenocorticotropic hormone stimulation test. Only 27 patients from 9 case reports in Japanese were eligible for inclusion in our study.
CONCLUSION
All published cases of MRHE as a cause of hyponatremia are described for the first time. In these cases, latent adrenal sufficiency might have been hidden and should have been excluded.
Topics: Aged; Hematologic Agents; Humans; Hyponatremia; Mineralocorticoids
PubMed: 28682868
DOI: 10.1097/MD.0000000000007154 -
Current Problems in Cardiology Jul 2024Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF).... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF.
MATERIALS AND METHODS
MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
Totally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]).
CONCLUSIONS
MRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.
Topics: Mineralocorticoid Receptor Antagonists; Humans; Heart Failure; Stroke Volume; Randomized Controlled Trials as Topic; Network Meta-Analysis; Spironolactone; Eplerenone; Treatment Outcome
PubMed: 38692445
DOI: 10.1016/j.cpcardiol.2024.102615 -
Age and Ageing Jan 2017Mineralocorticoid receptor antagonists (MRAs) improve outcomes in several populations of patients with heart failure (HF), but there has been no systematic review of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mineralocorticoid receptor antagonists (MRAs) improve outcomes in several populations of patients with heart failure (HF), but there has been no systematic review of MRAs in older patients.
OBJECTIVES
Systematic review and meta-analysis of the efficacy and safety of MRA treatment in elderly HF patients.
DATA SOURCES
Trials were identified through a literature search until 24 January 2015.
STUDY SELECTION
Randomised controlled trials (RCTs) of MRAs in patients with HF and/or left ventricular systolic dysfunction aged ≥65 years, with subgroup analysis of patients ≥65 years or with mean participant age ≥70 years.
DATA EXTRACTION AND SYNTHESIS
Efficacy outcomes were mortality, hospitalisation for cardiovascular causes, symptom status or functional capacity. Safety outcomes were hyperkalaemia and renal dysfunction. Data were analysed using relative risk ratios with 95% confidence intervals. Relative risk ratios were pooled where more than three estimates were available.
RESULTS
Seven RCTs were included (total n = 8,638). Three RCTs in HF with reduced ejection fraction (HEFREF) reported overall benefit from MRA therapy with no significant treatment interaction for age; the effects of MRAs on mortality in patients ≥75 years displayed marked inter-study heterogeneity. In four RCTs of HF with preserved ejection fraction (HEFPEF), MRA treatment had no significant effect on any efficacy outcome.
CONCLUSION
MRAs improve clinical outcomes in selected cohorts of older patients with HEFREF but not HEFPEF. In patients ≥75 years with HEFREF, the effect of MRA treatment on overall mortality is uncertain. Further study is required in subgroups of elderly patients with both HEFREF and HEFPEF.
Topics: Age Factors; Aged; Aged, 80 and over; Aging; Chi-Square Distribution; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Odds Ratio; Risk Factors; Stroke Volume; Treatment Outcome; Ventricular Function, Left
PubMed: 28181634
DOI: 10.1093/ageing/afw138 -
Diabetes, Obesity & Metabolism Oct 2023To explore whether the beneficial cardiovascular (CV) effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors is consistent with or without concurrent use of CV... (Meta-Analysis)
Meta-Analysis
AIM
To explore whether the beneficial cardiovascular (CV) effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors is consistent with or without concurrent use of CV medications in patients with type 2 diabetes, heart failure (HF) or chronic kidney disease.
METHODS
We searched Medline and Embase up to September 2022 for CV outcomes trials. The primary endpoint was the composite of cardiovascular (CV) death or hospitalization for HF. Secondary outcomes included the individual components of CV death, hospitalization for HF, death from any cause, major adverse CV events or renal events, volume depletion and hyperkalaemia. We pooled hazard ratios (HRs) and risk ratios alongside 95% confidence intervals (CIs).
RESULTS
We included 12 trials comprising 83 804 patients. SGLT-2 inhibitors reduced the risk of CV death or hospitalization for HF regardless of background use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), b-blockers, diuretics, mineralocorticoid receptor antagonists (MRAs), or triple combination therapy of either an ACEI/ARB plus b-blocker plus MRA, or an ARNI plus b-blocker plus MRA (HRs ranged from 0.61 to 0.83; P > .1 for each subgroup interaction). Similarly, no subgroup differences were evident for most analyses for the secondary outcomes of CV death, hospitalization for HF, all-cause mortality, major adverse CV or renal events, hyperkalaemia and volume depletion rate.
CONCLUSIONS
The benefit of SGLT-2 inhibitors seems to be additive to background use of CV medications in a broad population of patients. These findings should be interpreted as hypothesis generating because most of the subgroups analysed were not prespecified.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Angiotensin Receptor Antagonists; Hyperkalemia; Heart Failure; Symporters; Glucose; Sodium; Cardiovascular Diseases
PubMed: 37435776
DOI: 10.1111/dom.15200 -
Eye (London, England) Apr 2021We performed a systematic review and meta-analysis to assess the efficacy and safety of the mineralocorticoid receptor antagonist (MRA) treatment for central serous... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We performed a systematic review and meta-analysis to assess the efficacy and safety of the mineralocorticoid receptor antagonist (MRA) treatment for central serous chorioretinopathy (CSC).
METHODS
We searched the PubMed, Embase, and the Cochrane Library to identify relevant clinical studies published prior to March 2020. The primary outcome was change in best-corrected visual acuity (BCVA), and the secondary outcomes included the subretinal fluid (SRF), subfoveal choroidal thickness (SFCT), and central macular thickness (CMT).
RESULTS
Five randomized controlled trials (RCT) and four cohort studies met the inclusion criteria with a total of 352 eyes. The MRA treatment was not superior to placebo in BCVA at 1 month (WMD = -0.06, 95% CI -0.15-0.02, P = 0.15, I = 86%), 3 months (WMD = -0.04, 95% CI -0.14-0.06, P = 0.44, I = 77%) and 6 months (WMD = -0, 95% CI -0.05-0.05, P = 0.92, I = 0%). The MRA treatment resulted in significant reduction than the placebo in the SRF (WMD = -60.64, 95% CI -97.91 to -23.37, P = 0.001, I = 49%), SFCT (WMD = -39.15, 95% CI -52.58 to -25.72, P < 0.001, I = 0%), and CMT (WMD = -60.75, 95% CI -97.85 to -23.65, P = 0.01, I = 53%).
CONCLUSIONS
Our meta-analysis shows that the MRA treatment can improve anatomical structure in CSC patients, but it is not effective for achieving BCVA gain. The applicant of the MRA is safe and have no severe effect.
Topics: Central Serous Chorioretinopathy; Humans; Mineralocorticoid Receptor Antagonists; Subretinal Fluid; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity
PubMed: 33414535
DOI: 10.1038/s41433-020-01338-4 -
BMC Nephrology Sep 2016Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease.
METHODS
We conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults.
RESULTS
Nineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (-5.7 [-9.0, -2.3] mmHg), diastolic blood pressure (-1.7 [-3.4, -0.1] mmHg) and glomerular filtration rate (-3.2 [-5.4, -1.0] mL/min/1.73 m(2)). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse.
CONCLUSIONS
Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Disease Progression; Glomerular Filtration Rate; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Patient Dropouts; Proteinuria; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Risk Assessment
PubMed: 27609359
DOI: 10.1186/s12882-016-0337-0