Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials

Yang, Panpan; Shen, Wen; Chen, Xi; Zhu, Dan; Xu, Xiaobo; Wu, Tao Cheng; Xu, Gaosi; Wu, Qinghua

doi:10.1007/s10741-019-09790-5

Cited by 18 publications

(11 citation statements)

References 33 publications

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“…MRA use increases sodium excretion and decreases potassium excretion in the kidney, resulting in an increase in serum potassium levels (35). Even though the incidence of hyperkalaemia was increased in comparison with that in the placebo group, finerenone is associated with a lower risk than classic steroidal MRAs (spironolactone or eplerenone) according to recent trials and meta-analyses (30,35,36). Current research has reported that compared with eplerenone, finerenone has a much better effect on preventing cardiac fibrosis and improving strain parameters in mice (37).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of finerenone in patients with chronic kidney disease: a systematic review with meta-analysis and trial sequential analysis

Fu¹,

Geng²,

Chi³

et al. 2021

Ann Palliat Med

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Background: The efficacy and safety of finerenone are unknown. Therefore, we performed this metaanalysis to investigate the efficacy and safety of finerenone in patients with chronic kidney disease (CKD).Methods: We systematically searched for relevant studies in the PubMed, Embase and Cochrane Library databases from database inception until December 2020. We selected randomized controlled trials assessing finerenone treatment in patients with CKD.Results: Four trials (n=7,048) met the inclusion criteria. Compared with placebo, finerenone significantly reduced the urine albumin-to-creatinine ratio (UACR) in patients with CKD {mean difference (MD), −0.30 [95% confidence interval (CI), −0.50, −0.11], P<0.05}, and trial sequential analysis (TSA) confirmed this result. No significant difference was observed in eGFR in patients with CKD between the finerenone and placebo groups [MD, −0.90 (95% CI, −3.84 to 2.04), P>0.05]. Overall, the frequency of adverse events was similar in the two groups [relative risk (RR), 1. 00 (95% CI, 0.98, 1.02), P>0.05], and TSA confirmed this result. However, the finerenone group exhibited a lower risk of cardiovascular disorders and a higher risk of hyperkalemia than the placebo group [RR, 0.92 (95% CI, 0.85, 0.99), P<0.05 and RR, 2.04 (95% CI, 1.77, 2.34), P<0.00001, respectively].Discussion: This meta-analysis indicated that finerenone confers an important antiproteinuric effect on patients with CKD and reduces the risk of cardiovascular disorders in these patients. Finerenone may be a promising therapy option for patients with CKD. PROSPERO registration number: CRD42021222404

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of finerenone in patients with chronic kidney disease: a systematic review with meta-analysis and trial sequential analysis

Fu¹,

Geng²,

Chi³

et al. 2021

Ann Palliat Med

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“…Treatment with these agents was associated with a significant decrease in day 4 ELT (indicating an increase in learning) and an increase in day 5 TSTQ (retrieval of learned things, that is, memory) in Aβ‐injected mice in Morris water maze test. Mineralocorticoid receptor antagonists are potassium‐sparing diuretics, and these are clinically employed in the management of congestive heart failure [3]. However, studies have shown their expanding spectrum in a number of diseases including diabetic nephropathy [5], treatment‐resistant hypertension [6].…”

Section: Discussionmentioning

confidence: 99%

“…Spironolactone and eplerenone are mineralocorticoid receptor blockers and have been employed in the clinics as potassium‐sparing diuretics. In clinics, these are predominantly used for the management of congestive heart failure and these have been reported to reduce cardiac remodeling and mortality rate in these patients [3]. Studies have shown their potential in modifying the pathogenesis of diseases including diabetic cardiomyopathy [4], diabetic nephropathy [5], treatment‐resistant hypertension [6], inflammasome formation [7], vascular dysfunction [8], and muscular dystrophy [9].…”

Section: Introductionmentioning

confidence: 99%

Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H₂S‐Nrf2 signaling

Chen

Shi

She

et al. 2020

Fundamemntal Clinical Pharma

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The present study explored the role and mechanisms of mineralocorticoid receptor antagonists in β‐amyloid (Aβ)‐induced cognitive impairment. A single intracerebroventricular injection of Aβ1‐42 was given to mice, and after 14 days of injection, memory was evaluated using the Morris water maze test. Spironolactone (25 and 50 mg/kg) and eplerenone (50 and 100 mg/kg) were administered for two days before and for 14 days after Aβ injection. Mineralocorticoid receptor blockers attenuated Aβ‐induced cognitive impairment assessed in terms of decrease in day 4 escape latency time (ELT) in comparison to day 1 ELT (suggesting an increase in learning) along with an increase in time spent in target quadrant on day 5 (suggesting the retrieval of learned things). These drugs also increased the expression of BDNF, H2S, Nrf2, reduced glutathione, and decreased β‐amyloid and TNF‐α in the frontal cortex and hippocampus. Co‐administration of ANA‐12, BDNF receptor antagonist (0.25 and 0.5 mg/kg) abolished cognitive improving functions of mineralocorticoid receptor blockers, attenuated H2S, Nrf2, reduced glutathione, and decreased β‐amyloid and TNF‐α. It is concluded that spironolactone and eplerenone attenuate cognitive decline of Alzheimer's type, possibly through upregulation of BDNF levels in the frontal cortex and hippocampus, which may increase H2S, decrease Aβ, activate Nrf2‐dependent antioxidant system, and decrease neuroinflammation.

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“…Third generation non-steroidal MRAs under development include finerenone, esaxerenone, aparenone and KBP-5074. These lack steroidal off-target effects and may also cause less hyperkalemia (18).…”

Section: Differences Between Mrasmentioning

confidence: 99%

When Off Target Effects Are On Target: The Role Of Spironolactone In Patients With COVID-19

Wilcox¹,

Pitt²

2021

Preprint

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Aims: Spironolactone is a steroidal mineralocoricosteroid receptor antagonist (MRA) used for treatment of resistant hypertension, heart failure and edema. It exerts class specific adverse effects that are shared by other MRAs. Additionally, it exerts unique “off target” steroidal effects that include gynecomastia, impotence and loss of libido in males and menstrual irregularity in females. Together, these have led to a poor tolerability and limited use despite positive results in many randomized, controlled clinical trials. We review the off-target effects of spironolactone that may summate with its MRA action to provide an advantageous profile for prevention or treatment of patients with COVID-19. Methods: Literature review using PubMed Central. Results: The blockade by spironolactone of the androgen receptor should diminish the expression of transmembrane protease serine 2 (TMPRSS2) that has an androgen promoter while its MRA action should enhance the expression of protease nexin1 (PN1) that inhibits furin and plasmin. TMPRSS2, furin and plasmin cooperated to process the SARS-CoV-2 spike protein to increase its high affinity binding to the angiotensin converting enzyme 2 (ACE2) and thereby promote viral cell entry. Its actions as an MRA may reduce inflammation and preserve pulmonary, cardiac and vascular functions. Its anti-plasmin action may combat hemostatic dysfunction. Conclusion: The hypothesis that the off-target effects of spironolactone summate with its MRA actions to provide special benefits for COVID-19 is worthy of direct investigation and clinical trial.

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Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials

Cited by 18 publications

References 33 publications

Efficacy and safety of finerenone in patients with chronic kidney disease: a systematic review with meta-analysis and trial sequential analysis

Efficacy and safety of finerenone in patients with chronic kidney disease: a systematic review with meta-analysis and trial sequential analysis

Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H₂S‐Nrf2 signaling

When Off Target Effects Are On Target: The Role Of Spironolactone In Patients With COVID-19

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Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials

Cited by 18 publications

References 33 publications

Efficacy and safety of finerenone in patients with chronic kidney disease: a systematic review with meta-analysis and trial sequential analysis

Efficacy and safety of finerenone in patients with chronic kidney disease: a systematic review with meta-analysis and trial sequential analysis

Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H2S‐Nrf2 signaling

When Off Target Effects Are On Target: The Role Of Spironolactone In Patients With COVID-19

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Mineralocorticoid receptor antagonist‐mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF‐H₂S‐Nrf2 signaling