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European Journal of Endocrinology Dec 2022In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy vs mineralocorticoid receptor antagonist (MRA) have not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy vs mineralocorticoid receptor antagonist (MRA) have not been compared yet. We aim to compare the clinical outcomes of these patients after treatment.
DESIGN AND METHODS
A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to 18 December 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA).
RESULTS
A total of 9 studies with 8473 adult patients with PA (≥18 years) were enrolled. A lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 (95% CI: 0.38-0.56), P < 0.001). We found a lower incidence of all-cause mortality (OR: 0.33 (95% CI: 0.15-0.73), P = 0.006) and MACE (OR: 0.55, (95% CI: 0.40-0.74), P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 (95% CI: 0.15-0.75), P = 0.008), arrhythmias (OR: 0.46 (95% CI: 0.27-0.81), P = 0.007), and congestive heart failure (OR: 0.52 (95% CI: 0.33-0.81), P = 0.004) was also lower in adrenalectomy group. The metaregression showed patient's age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 (95% CI: 1.005-1.169), P = 0.036). TSA demonstrated that the accrued sample size and effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence.
CONCLUSIONS
In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.
Topics: Adult; Humans; Adrenalectomy; Heart Failure; Hyperaldosteronism; Mineralocorticoid Receptor Antagonists
PubMed: 36315466
DOI: 10.1530/EJE-22-0375 -
Diabetes & Metabolic Syndrome Oct 2022Finerenone is a novel non-steroidal mineralocorticoid antagonist (MRA) recently approved for the treatment of chronic kidney disease (CKD) in people with type 2 diabetes... (Review)
Review
BACKGROUND & AIMS
Finerenone is a novel non-steroidal mineralocorticoid antagonist (MRA) recently approved for the treatment of chronic kidney disease (CKD) in people with type 2 diabetes (T2D). We aim to conduct a systematic review of finerenone to know the efficacy and safety of finerenone in CKD with or without T2D.
METHODS
A systematic search in the electronic database of PubMed and Google Scholar was made from inception until September 09, 2022, using several MeSH keywords related to finerenone. Ongoing trials were additionally searched from ClinicalTrials.Gov.
RESULTS
Five phase 2 and three phase 3, randomized, double-blind, placebo- or active-controlled studies of finerenone have been published to date and several other randomized and real-world studies of finerenone are currently undergoing.
CONCLUSIONS
In short-term studies in patients with CKD and reduced ejection heart failure, with or without T2D, finerenone 20 mg appears to have a better renal outcome compared with spironolactone and a better mortality outcome compared with eplerenone, with significantly lesser hyperkalemia compared to both spironolactone and finerenone. In long-term studies in patients with CKD and T2D, finerenone 10/20 mg significantly reduces the progression of renal disease and reduced CV endpoints (especially heart failure hospitalization) compared to placebo. Finerenone has no effect on HbA1c, body weight, and sexual side effects including gynecomastia, and has only a modest effect on blood pressure. However, hyperkalemia leading to drug withdrawal was significantly higher with finerenone compared to placebo. Safety data in real-world settings is a pressing priority.
Topics: Male; Humans; Mineralocorticoid Receptor Antagonists; Diabetic Nephropathies; Eplerenone; Spironolactone; Hyperkalemia; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Heart Failure; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 36223666
DOI: 10.1016/j.dsx.2022.102638 -
American Journal of Hypertension Feb 2023The rates of uncontrolled hypertension, along with downstream cardiovascular outcomes, has been worsening in this country. Despite the plethora of antihypertensive...
BACKGROUND
The rates of uncontrolled hypertension, along with downstream cardiovascular outcomes, has been worsening in this country. Despite the plethora of antihypertensive medications on the market, the prevalence of resistant hypertension (RH) is estimated to be 13.7%. Therefore in addition to increased clinical education and focus on lifestyle management of hypertension and medication compliance, new therapies are needed to address this rise in hypertension.
METHODS
A systematic review of the available medical literature was performed to identify emerging treatment options for RH.
RESULTS
Six different pharmacologic classes and 2 procedural interventions were identified as being appropriate for review in this paper. The pharmacologic classes to be explored are non-steroidal mineralocorticoid receptor antagonists, aminopeptidase A inhibitors, dual endothelin antagonists, aldosterone synthetase inhibitors, atrial natriuretic peptide inhibitors, and attenuators of hepatic angiotensinogen. Discussion of procedural interventions to lower blood pressure will focus on renal denervation and devices that increase carotid baroreceptor activity.
CONCLUSIONS
Promising medication and procedural interventions are being developed and studied to expand our treatment arsenal for patients with uncontrolled essential hypertension and RH.
Topics: Humans; Hypertension; Antihypertensive Agents; Blood Pressure; Kidney; Pressoreceptors
PubMed: 36201204
DOI: 10.1093/ajh/hpac111 -
Frontiers in Pharmacology 2022Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease (ESRD). To evaluate the efficacy and safety of different types of mineralocorticoid...
Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease (ESRD). To evaluate the efficacy and safety of different types of mineralocorticoid receptor antagonists (MRAs) in diabetic kidney disease patients, we conducted this network meta-analysis by performing a systematic search in PubMed, MEDLINE, EMBASE, Web of Science, the Cochrane Library, and Clinicaltrials.gov. A total of 12 randomized clinical trials with 15,492 patients applying various types of MRAs covering spironolactone, eplerenone, finerenone, esaxerenone, and apararenone were included. The efficacy outcomes were the ratio of urine albumin creatine ratio (UACR) at posttreatment vs. at baseline, change in posttreatment estimated glomerular filtration (eGFR) vs. at baseline, and change in posttreatment systolic blood pressure (SBP) vs. at baseline. The safety outcome was the number of patients suffering from hyperkalemia. High-dose finerenone (MD -0.31, 95% CI: -0.52, -0.11), esaxerenone (MD -0.54, 95% CI: -0.72, -0.30), and apararenone (MD -0.63, 95% CI: -0.90, -0.35) were associated with a superior reduction in proteinuria in patients with DKD. Regarding the change in eGFR, the results of all drugs were similar, and finerenone may have potential superiority in protecting the kidney. Compared with placebo, none of the treatments was associated with a higher probability of controlling systolic blood pressure during treatment. Moreover, spironolactone, esaxerenone, and 20 mg of finerenone presented a higher risk of hyperkalemia. This Bayesian network meta-analysis was the first to explore the optimal alternative among MRAs in the treatment of DKD and revealed the superiority of 20 mg of finerenone among MRAs in treating DKD. PROSPERO, identifier (CRD42022313826).
PubMed: 36188560
DOI: 10.3389/fphar.2022.967317 -
Acta Ophthalmologica Mar 2023Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult... (Meta-Analysis)
Meta-Analysis Review
Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when trials compare active treatments without any placebo/control group. In this study, we systematically reviewed short-term efficacies of any cCSC treatment tested in randomized controlled trials (RCT) and employed network meta-analyses to compare to non-treatment controls. We searched 11 literature databases on 20 March 2022 for RCTs of treatment of cCSC. We identified 17 RCTs including a total of 1172 eyes. Treatments included conventional laser (44 eyes), half-dose or half-fluence photodynamic therapy (PDT) (298 eyes), ranibizumab (16 eyes), antioxidants (50 eyes), mineralocorticoid receptor antagonists (187 eyes), rifampicin (91 eyes), selective retina therapy (SRT) (67 eyes) and subthreshold micropulse laser (192 eyes). Compared with controls, significant benefit on complete subretinal fluid resolution was only obtained from half-dose or half-fluence PDT (OR: 20.6; 95% CI: 6.3-66.7; p < 0.0001) and conventional laser (OR: 36.4; 95% CI: 2.0-655.7; p = 0.015), and at an order of magnitude lower degree from SRT (OR: 3.4; 95% CI: 1.7-6.8; p = 0.00075). Compared with controls and after sensitivity analyses, significant benefit in the change in best-corrected visual acuity was only obtained by half-dose/-fluence PDT (-0.13 logMAR; 95% CI: -0.20 to -0.06 logMAR; p = 0.00021). In conclusion, three treatment options provide significant improvement over no treatment: half-dose/-fluence PDT, conventional laser and to a much lesser degree SRT. Considering that conventional laser can only be applied for extrafoveal leaks, and the long-term data available for PDT-based treatments finding persisting treatment results, half-dose or half-fluence PDT is the only viable treatment option for patients with cCSC. Shortage issues with verteporfin should not lead to employment of ineffective treatment modalities, as they put patients at unnecessary risk of adverse events.
Topics: Humans; Photosensitizing Agents; Central Serous Chorioretinopathy; Photochemotherapy; Network Meta-Analysis; Porphyrins; Visual Acuity; Fluorescein Angiography; Treatment Outcome; Tomography, Optical Coherence; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 36178171
DOI: 10.1111/aos.15263 -
Cureus Jul 2022The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys... (Review)
Review
Effects of Renin-Angiotensin-Aldosterone System Inhibition on Left Ventricular Hypertrophy, Diastolic Function, and Functional Status in Patients With Hypertrophic Cardiomyopathy: A Systematic Review.
The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys produce renin which converts angiotensinogen to angiotensin-1 (AT-I) and angiotensin-converting enzyme (ACE) to angiotensin-II (AT-II). AT-II binds to receptors in the adrenal cortex to release aldosterone. AT-II and aldosterone promote water and salt retention, vascular tone, and myocardial contractility. These physiological changes raise blood pressure and circulation. Reduced renal perfusion pressure sensed by baroreceptors and the sympathetic nervous system's β-adrenergic receptors trigger renin release and RAAS activation. RAAS restores hemodynamic stability in pathological states associated with low perfusion. This adaptive response is important for restoring perfusion and hemodynamic stability, but prolonged RAAS activation has deleterious effects on the cardiovascular system. Long-term mineralocorticoid exposure has been linked to left ventricular hypertrophy (LVH) and remodeling. AT-II activates fibroblasts and cardiac myocytes to promote cardiac remodeling. Blocking RAAS can eliminate the long-term negative effects of RAAS activation. Direct renin inhibitors, ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists are RAAS blockers. RAAS blockade improves mortality and hospitalization in systolic heart failure and acute myocardial infarction. RAAS blockade has not demonstrated the same benefits in other cardiac populations, such as those with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) causes LVH and asymmetric septal hypertrophy. When the outflow tract gradient exceeds 30 mmHg and is associated with septal hypertrophy, it is known as obstructive HCM. Dyspnea on exertion, syncope, and exertional angina are symptoms of HCM. RAAS activation worsens LVH by increasing blood pressure and by directly affecting cardiac myocytes with AT-II and aldosterone. RAAS blockade reverses myocardial fibrosis and slows HCM progression in animal models. We performed a meta-analysis of randomized clinical trials to further investigate the potential benefit of RAAS blockade in HCM patients. Although our findings included significant results for some of the RAAS blockade agents, these findings were not consistent throughout all the studies. Mavacamten, one of the newest treatments, has shown promising outcomes.
PubMed: 35949750
DOI: 10.7759/cureus.26642 -
Frontiers in Cardiovascular Medicine 2022Percutaneous mitral valve repair (PMVR) provides an available choice for patients suffering from secondary mitral regurgitation (SMR), especially those whose symptoms...
BACKGROUND
Percutaneous mitral valve repair (PMVR) provides an available choice for patients suffering from secondary mitral regurgitation (SMR), especially those whose symptoms persist after optimal, conventional, heart-failure therapy. However, conflicting results from clinical trials have created a problem in identifying patients who will benefit the most from PMVR.
OBJECTIVE
To pool mortality data and assess clinical predictors after PMVR among patients with SMR. To this end, subgroup and meta-regression analyses were additionally performed.
METHODS
We searched PubMed, EMBASE, and Cochrane databases, and 13 studies were finally included for meta-analysis. Estimated mortality and 95% confidence intervals (CIs) were obtained using a random-effects proportional meta-analysis. We also carried out a meta-regression analysis to clarify the potential influence of important covariates on mortality.
RESULTS
A total of 1,259 patients with SMR who had undergone PMVR were enrolled in our meta-analysis. The long-term estimated pooled mortality of PMVR was 19.3% (95% CI: 13.6-25.1). Meta-regression analysis showed that mortality was directly proportional to cardiac resynchronization therapy (CRT) (β = 0.009; 95% CI: 0.002-0.016; = 0.009), an effective regurgitant orifice (ERO) (β = 0.009; 95% CI: 0.000-0.018; = 0.047), and a mineralocorticoid receptor antagonist (MRA) use (β = -0.015; 95% CI: -0.023--0.006; < 0.001). Subgroup analysis indicated that patients with preexisting AF (β = -0.002; 95% CI: -0.005- -0.000; = 0.018) were associated with decreased mortality if they received a mitral annuloplasty device. Among the edge-to-edge repair device group, a higher left ventricular (LV) ejection fraction, or lower LV end-systolic diameter, LV end-systolic volume, and LV end-diastolic volume were proportional to lower mortality.
CONCLUSION AND RELEVANCE
The pooled mortality of PMVR was 19.3% (95% CI: 13.6-25.1). Further meta-regression indicated that AF was associated with a better outcome in conjunction with the use of a mitral annuloplasty device, while better LV functioning predicted a better outcome after the implantation of an edge-to-edge repair device.
PubMed: 35859589
DOI: 10.3389/fcvm.2022.918712 -
Frontiers in Pharmacology 2022The non-steroidal mineralocorticoid receptor antagonists (MRAs) are promising treatments in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We...
Efficacy and Safety of Non-Steroidal Mineralocorticoid Receptor Antagonists in Patients With Chronic Kidney Disease and Type 2 Diabetes: A Systematic Review Incorporating an Indirect Comparisons Meta-Analysis.
The non-steroidal mineralocorticoid receptor antagonists (MRAs) are promising treatments in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We conducted a meta-analysis to explore the efficacy and safety of the non-steroidal MRAs (finerenone, apararenone, esaxerenone) and detect the differences among them. We searched several databases for eligible randomized controlled trials (RCTs) investigating non-steroidal MRAs versus placebo in patients with CKD and T2D. We performed a conventional meta-analysis separately, and then indirect comparisons for efficacy and safety outcomes were conducted among these included drugs. Eight RCTs with 14,450 subjects were enrolled. In patients with CKD and T2D, a greater reduction in urinary albumin-to-creatinine ratio (UACR) (WMD -0.40, 95% CI -0.48 to -0.32, < 0.001), estimated glomerular filtration rate (eGFR) (WMD -2.69, 95% CI -4.47 to -0.91, = 0.003), systolic blood pressure (SBP) (WMD -4.84, 95% CI -5.96 to -3.72, < 0.001) and a higher risk of hyperkalemia (RR 2.07, 95% CI 1.86 to 2.30, < 0.001) were observed in the non-steroidal MRAs versus placebo; there is no significant difference in the incidence of serious adverse events between two groups (RR 1.32, 95% CI 0.98 to 1.79, = 0.067). Compared with finerenone, esaxerenone showed no significant difference in UACR reduction (WMD 0.24, 95% CI -0.016 to 0.496, = 0.869); apararenone and esaxerenone showed greater decreases in SBP (WMD 1.37, 95% CI 0.456 to 2.284, = 0.010; WMD 3.11, 95% CI 0.544 to 5,676, = 0.021). Despite the moderate increased risk of hyperkalemia, use of non-steroidal MRAs could reduce proteinuria and SBP in patients with CKD and T2D. In terms of renoprotection, esaxerenone and finerenone may have similar effects. Esaxerenone and apararenone may have better antihypertensive effects than finerenone. The head-to-head RCTs are still needed to compare the differences of the efficacy and safety in these non-steroidal MRAs.
PubMed: 35784710
DOI: 10.3389/fphar.2022.896947 -
Frontiers in Cardiovascular Medicine 2022Sudden cardiac death (SCD) is a global public health issue, accounting for 10-20% of deaths in industrialized countries. Identification of modifiable risk factors may...
BACKGROUND
Sudden cardiac death (SCD) is a global public health issue, accounting for 10-20% of deaths in industrialized countries. Identification of modifiable risk factors may reduce SCD incidence.
METHODS
This umbrella review systematically evaluates published meta-analyses of observational and randomized controlled trials (RCT) for the association of modifiable risk and protective factors of SCD.
RESULTS
Fifty-five meta-analyses were included in the final analysis, of which 31 analyzed observational studies and 24 analyzed RCTs. Five associations of meta-analyses of observational studies presented convincing evidence, including three risk factors [diabetes mellitus (DM), smoking, and early repolarization pattern (ERP)] and two protective factors [implanted cardiac defibrillator (ICD) and physical activity]. Meta-analyses of RCTs identified five protective factors with a high level of evidence: ICDs, mineralocorticoid receptor antagonist (MRA), beta-blockers, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with HF. On the contrary, other established, significant protective agents [i.e., amiodarone and statins along with angiotensin-converting enzyme (ACE) inhibitors in heart failure (HF)], did not show credibility. Likewise, risk factors as left ventricular ejection fraction in HF, and left ventricular hypertrophy, non-sustain ventricular tachycardia, history of syncope or aborted SCD in pediatric patients with hypertrophic cardiomyopathy, presented weak or no evidence.
CONCLUSIONS
Lifestyle risk factors (physical activity, smoking), comorbidities like DM, and electrocardiographic features like ERP constitute modifiable risk factors of SCD. Alternatively, the use of MRA, beta-blockers, SGLT-2 inhibitors, and ICD in patients with HF are credible protective factors. Further investigation targeted in specific populations will be important for reducing the burden of SCD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216363, PROSPERO CRD42020216363.
PubMed: 35783841
DOI: 10.3389/fcvm.2022.848021 -
Applied Neuropsychology. Adult 2023Addison's disease (AD) entails a chronic insufficient production of gluco- and mineralocorticoids. Fatigue and decreased quality of life are frequently reported...
Addison's disease (AD) entails a chronic insufficient production of gluco- and mineralocorticoids. Fatigue and decreased quality of life are frequently reported symptoms, but little is known about its effects on cognition. This study aims to explore the existence of cognitive impairment in patients with AD and the influence of treatment regimens. We conducted a systematic review. Inclusion criteria were met by 10 articles, most of them ranked as intermediate quality. Three studies analyzed the relationship between AD and cognitive impairment; one explored the effect of delaying treatment showing no effect on cognitive performance, and another one studied the effect of fludrocortisone treatment. Episodic memory was the most frequent cognitive domain impaired across studies, in comparison to healthy controls. Two papers investigated the relationship between impaired sleep quality and poor cognitive performance. Two studies related cognitive impairments with hypocortisolism-derived brain neuroglycopenia. Two studies investigated the effect of DHEA substitution. In conclusion, patients exhibit a moderately reduced performance in verbal learning. The pathophysiology of this impairment is likely multifactorial. Future studies should include larger sample sizes, the use of comprehensive and multi-domain neuropsychological and behavioral protocols, and neuroimaging.
PubMed: 35767730
DOI: 10.1080/23279095.2022.2090256