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Endocrine Reviews Jan 2024Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and... (Review)
Review
Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed.
Topics: Humans; Aldosterone; Hyperaldosteronism; Renin; Hypertension; Mineralocorticoid Receptor Antagonists; Biomarkers
PubMed: 37439256
DOI: 10.1210/endrev/bnad024 -
The Cochrane Database of Systematic... Jul 2023Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity... (Review)
Review
BACKGROUND
Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences.
OBJECTIVES
To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering.
SEARCH METHODS
Cochrane Hypertension's Information Specialist searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, and trials registers to March 2021. We also checked references and contacted study authors to identify additional studies. A top-up search of the Specialized Register was carried out in June 2022.
SELECTION CRITERIA
Randomized active comparator trials of at least one year's duration were included. Trials had a clearly defined intervention arm of a first-line diuretic (thiazide, thiazide-like, or loop diuretic) compared to another first-line drug class: beta-blockers, calcium channel blockers, alpha adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. Studies had to include clearly defined mortality and morbidity outcomes (serious adverse events, total cardiovascular events, stroke, coronary heart disease (CHD), congestive heart failure, and withdrawals due to adverse effects).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included 20 trials with 26 comparator arms randomizing over 90,000 participants. The findings are relevant to first-line use of drug classes in older male and female hypertensive patients (aged 50 to 75) with multiple co-morbidities, including type 2 diabetes. First-line thiazide and thiazide-like diuretics were compared with beta-blockers (six trials), calcium channel blockers (eight trials), ACE inhibitors (five trials), and alpha-adrenergic blockers (three trials); other comparators included angiotensin II receptor blockers, aliskiren (a direct renin inhibitor), and clonidine (a centrally acting drug). Only three studies reported data for total serious adverse events: two studies compared diuretics with calcium channel blockers and one with a direct renin inhibitor. Compared to first-line beta-blockers, first-line thiazides probably result in little to no difference in total mortality (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.84 to 1.10; 5 trials, 18,241 participants; moderate-certainty), probably reduce total cardiovascular events (5.4% versus 4.8%; RR 0.88, 95% CI 0.78 to 1.00; 4 trials, 18,135 participants; absolute risk reduction (ARR) 0.6%, moderate-certainty), may result in little to no difference in stroke (RR 0.85, 95% CI 0.66 to 1.09; 4 trials, 18,135 participants; low-certainty), CHD (RR 0.91, 95% CI 0.78 to 1.07; 4 trials, 18,135 participants; low-certainty), or heart failure (RR 0.69, 95% CI 0.40 to 1.19; 1 trial, 6569 participants; low-certainty), and probably reduce withdrawals due to adverse effects (10.1% versus 7.9%; RR 0.78, 95% CI 0.71 to 0.85; 5 trials, 18,501 participants; ARR 2.2%; moderate-certainty). Compared to first-line calcium channel blockers, first-line thiazides probably result in little to no difference in total mortality (RR 1.02, 95% CI 0.96 to 1.08; 7 trials, 35,417 participants; moderate-certainty), may result in little to no difference in serious adverse events (RR 1.09, 95% CI 0.97 to 1.24; 2 trials, 7204 participants; low-certainty), probably reduce total cardiovascular events (14.3% versus 13.3%; RR 0.93, 95% CI 0.89 to 0.98; 6 trials, 35,217 participants; ARR 1.0%; moderate-certainty), probably result in little to no difference in stroke (RR 1.06, 95% CI 0.95 to 1.18; 6 trials, 35,217 participants; moderate-certainty) or CHD (RR 1.00, 95% CI 0.93 to 1.08; 6 trials, 35,217 participants; moderate-certainty), probably reduce heart failure (4.4% versus 3.2%; RR 0.74, 95% CI 0.66 to 0.82; 6 trials, 35,217 participants; ARR 1.2%; moderate-certainty), and may reduce withdrawals due to adverse effects (7.6% versus 6.2%; RR 0.81, 95% CI 0.75 to 0.88; 7 trials, 33,908 participants; ARR 1.4%; low-certainty). Compared to first-line ACE inhibitors, first-line thiazides probably result in little to no difference in total mortality (RR 1.00, 95% CI 0.95 to 1.07; 3 trials, 30,961 participants; moderate-certainty), may result in little to no difference in total cardiovascular events (RR 0.97, 95% CI 0.92 to 1.02; 3 trials, 30,900 participants; low-certainty), probably reduce stroke slightly (4.7% versus 4.1%; RR 0.89, 95% CI 0.80 to 0.99; 3 trials, 30,900 participants; ARR 0.6%; moderate-certainty), probably result in little to no difference in CHD (RR 1.03, 95% CI 0.96 to 1.12; 3 trials, 30,900 participants; moderate-certainty) or heart failure (RR 0.94, 95% CI 0.84 to 1.04; 2 trials, 30,392 participants; moderate-certainty), and probably reduce withdrawals due to adverse effects (3.9% versus 2.9%; RR 0.73, 95% CI 0.64 to 0.84; 3 trials, 25,254 participants; ARR 1.0%; moderate-certainty). Compared to first-line alpha-blockers, first-line thiazides probably result in little to no difference in total mortality (RR 0.98, 95% CI 0.88 to 1.09; 1 trial, 24,316 participants; moderate-certainty), probably reduce total cardiovascular events (12.1% versus 9.0%; RR 0.74, 95% CI 0.69 to 0.80; 2 trials, 24,396 participants; ARR 3.1%; moderate-certainty) and stroke (2.7% versus 2.3%; RR 0.86, 95% CI 0.73 to 1.01; 2 trials, 24,396 participants; ARR 0.4%; moderate-certainty), may result in little to no difference in CHD (RR 0.98, 95% CI 0.86 to 1.11; 2 trials, 24,396 participants; low-certainty), probably reduce heart failure (5.4% versus 2.8%; RR 0.51, 95% CI 0.45 to 0.58; 1 trial, 24,316 participants; ARR 2.6%; moderate-certainty), and may reduce withdrawals due to adverse effects (1.3% versus 0.9%; RR 0.70, 95% CI 0.54 to 0.89; 3 trials, 24,772 participants; ARR 0.4%; low-certainty). For the other drug classes, data were insufficient. No antihypertensive drug class demonstrated any clinically important advantages over first-line thiazides.
AUTHORS' CONCLUSIONS
When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.
Topics: Aged; Female; Humans; Male; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Diabetes Mellitus, Type 2; Diuretics; Heart Failure; Hypertension; Stroke; Thiazides; Middle Aged
PubMed: 37439548
DOI: 10.1002/14651858.CD008161.pub3 -
Lancet (London, England) Jan 2024Excess aldosterone accelerates chronic kidney disease progression. This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Excess aldosterone accelerates chronic kidney disease progression. This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection.
METHODS
This was a multinational, randomised, controlled, phase 2 trial. People aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 30 to less than 90 mL/min/1·73 m, a urine albumin to creatinine ratio (UACR) of 200 to less than 5000 mg/g, and serum potassium of 4·8 mmol/L or less, taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, were enrolled. Participants were randomly assigned (1:1) to 8 weeks of empagliflozin or placebo run-in, followed by a second randomisation (1:1:1:1) to 14 weeks of treatment with once per day BI 690517 at doses of 3 mg, 10 mg, or 20 mg, or placebo. Study participants, research coordinators, investigators, and the data coordinating centre were masked to treatment assignment. The primary endpoint was the change in UACR measured in first morning void urine from baseline (second randomisation) to the end of treatment. This study is registered with ClinicalTrials.gov (NCT05182840) and is completed.
FINDINGS
Between Feb 18 and Dec 30, 2022, of the 714 run-in participants, 586 were randomly assigned to receive BI 690517 or placebo. At baseline, 33% (n=196) were women, 67% (n=390) were men, 42% (n=244) had a racial identity other than White, and mean participant age was 63·8 years (SD 11·3). Mean baseline eGFR was 51·9 mL/min/1·73 m (17·7) and median UACR was 426 mg/g (IQR 205 to 889). Percentage change in first morning void UACR from baseline to the end of treatment at week 14 was -3% (95% CI -19 to 17) with placebo, -22% (-36 to -7) with BI 690517 3 mg, -39% (-50 to -26) with BI 690517 10 mg, and -37% (-49 to -22) with BI 690517 20 mg monotherapy. BI 690517 produced similar UACR reductions when added to empagliflozin. Investigator-reported hyperkalaemia occurred in 10% (14/146) of those in the BI 690517 3 mg group, 15% (22/144) in the BI 690517 10 mg group, and 18% (26/146) in the BI 690517 20 mg group, and in 6% (nine of 147) of those receiving placebo, with or without empagliflozin. Most participants with hyperkalaemia did not require intervention (86% [72/84]). Adrenal insufficiency was an adverse event of special interest reported in seven of 436 study participants (2%) receiving BI 690517 and one of 147 participants (1%) receiving matched placebo. No treatment-related deaths occurred during the study.
INTERPRETATION
BI 690517 dose-dependently reduced albuminuria with concurrent renin-angiotensin system inhibition and empagliflozin, suggesting an additive efficacy for chronic kidney disease treatment without unexpected safety signals.
FUNDING
Boehringer Ingelheim.
Topics: Aged; Female; Humans; Male; Middle Aged; Benzhydryl Compounds; Cytochrome P-450 CYP11B2; Double-Blind Method; Glucosides; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 38109916
DOI: 10.1016/S0140-6736(23)02408-X -
Clinical Journal of the American... Oct 2023In contrast to significant advances in the management of patients with chronic heart failure over the past few years, there has been little change in how patients with... (Review)
Review
In contrast to significant advances in the management of patients with chronic heart failure over the past few years, there has been little change in how patients with acute heart failure are treated. Symptoms and signs of fluid overload are the primary reason for hospitalization of patients who experience acute decompensation of heart failure. Intravenous loop diuretics remain the mainstay of therapy in this patient population, with a significant subset of them showing suboptimal response to these agents leading to incomplete decongestion at the time of discharge. Combination diuretic therapy, that is, using loop diuretics along with an add-on agent, is a widely applied strategy to counter renal sodium avidity through sequential blockade of sodium absorption within renal tubules. The choice of the second diuretic is affected by several factors, including the site of action, the anticipated secondary effects, and the available evidence on their efficacy and safety. While the current guidelines recommend combination diuretic therapy as a viable option to overcome suboptimal response to loop diuretics, it is also acknowledged that this strategy is not supported by strong evidence and remains an area of uncertainty. The recent publication of landmark studies has regenerated the interest in sequential nephron blockade. In this article, we provide an overview of the results of the key studies on combination diuretic therapy in the setting of acute heart failure and discuss their findings primarily with regard to the effect on renal sodium avidity and cardiorenal outcomes.
Topics: Humans; Diuretics; Heart Failure; Kidney; Sodium; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 37102974
DOI: 10.2215/CJN.0000000000000188 -
American Journal of Kidney Diseases :... Dec 2023Concerns about hyperkalemia may result in the underuse of established and novel therapies that improve kidney and/or cardiovascular (CV) outcomes in patients with type 2... (Review)
Review
Concerns about hyperkalemia may result in the underuse of established and novel therapies that improve kidney and/or cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Hyperkalemia-related issues are of particular relevance in patients with CKD, who are commonly receiving other hyperkalemia-inducing agents such as renin-angiotensin-aldosterone system inhibitors and nonsteroidal mineralocorticoid receptor antagonists. In contrast, sodium/glucose transporter 2 (SGLT2) inhibitors mitigate the risk of serious hyperkalemia in clinical trials. We aim to review recent evidence surrounding the risk of hyperkalemia in patients with T2DM and CKD treated with established and novel therapies for diabetic kidney disease, focusing on SGLT2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists. We conclude that SGLT2 inhibitors can be used safely in patients with T2DM at high CV risk with CKD without increasing the risk of hyperkalemia. Routine potassium monitoring is generally required when finerenone is used as a kidney- and CV-protective agent in patients with T2DM. Based on existing data, when added to the standard of care, combining SGLT2 inhibitors with finerenone is safe and has the potential to exert additional cardiorenal benefits in patients with diabetic kidney disease. The use of potassium binders should be considered to enable optimal doses of guideline-based therapies for patients with diabetic kidney disease to maximize the kidney and CV benefits.
Topics: Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Sodium-Glucose Transporter 2 Inhibitors; Renal Insufficiency, Chronic; Potassium
PubMed: 37517546
DOI: 10.1053/j.ajkd.2023.04.015 -
Journal of the American College of... Apr 2024The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals.
OBJECTIVES
The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF.
METHODS
In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee.
RESULTS
For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period.
CONCLUSIONS
Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).
Topics: Humans; Sodium Potassium Chloride Symporter Inhibitors; Acute Disease; Heart Failure; Diuretics; Benzhydryl Compounds; Glucosides
PubMed: 38569758
DOI: 10.1016/j.jacc.2024.02.009 -
Heart Failure Reviews Sep 2023Multiple landmark trials have helped to advance the treatment of heart failure with reduced ejection fraction (HFrEF) significantly over the past decade. These trials... (Review)
Review
Multiple landmark trials have helped to advance the treatment of heart failure with reduced ejection fraction (HFrEF) significantly over the past decade. These trials have led to the introduction of four main drug classes into the 2021 ESC guideline, namely angiotensin-receptor neprilysin inhibitors/angiotensin-converting-enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. The life-saving effect of these therapies has been shown to be additive and becomes apparent within weeks, which is why maximally tolerated or target doses of all drug classes should be strived for as quickly as possible. Recent evidence, such as the STRONG-HF trial, demonstrated that rapid drug implementation and up-titration is superior to the traditional and more gradual step-by-step approach where valuable time is lost to up-titration. Accordingly, multiple rapid drug implementation and sequencing strategies have been proposed to significantly reduce the time needed for the titration process. Such strategies are urgently needed since previous large-scale registries have shown that guideline-directed medical therapy (GDMT) implementation is a challenge. This challenge is reflected by generally low adherence rates, which can be attributed to factors considering the patient, health care system, and local hospital/health care provider. This review of the four medication classes used to treat HFrEF seeks to present a thorough overview of the data supporting current GDMT, discuss the obstacles to GDMT implementation and up-titration, and identify multiple sequencing strategies that could improve GDMT adherence. Sequencing strategies for GDMT implementation. GDMT: guideline-directed medical therapy; ACEi: angiotensin-converting enzyme inhibitor; ARB: Angiotensin II receptor blocker; ARNi: angiotensin receptor-neprilysin inhibitor; BB: beta-blocker; MRA: mineralocorticoid receptor antagonist; SGLT2i: sodium-glucose co-transporter 2 inhibitor.
Topics: Humans; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Heart Failure; Mineralocorticoid Receptor Antagonists; Neprilysin; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume
PubMed: 37311917
DOI: 10.1007/s10741-023-10325-2 -
Redox Biology Dec 2023Diabetic tubulopathy (DT) is a recently recognized key pathology of diabetic kidney disease (DKD). The mitochondria-centric view of DT is emerging as a vital...
Diabetic tubulopathy (DT) is a recently recognized key pathology of diabetic kidney disease (DKD). The mitochondria-centric view of DT is emerging as a vital pathological factor in different types of metabolic diseases, such as DKD. Finerenone (FIN), a novel non-steroidal mineralocorticoid receptor antagonist, attenuates kidney inflammation and fibrosis in DKD, but the precise pathomechanisms remain unclear. The role of mineralocorticoid receptor (MR) in perturbing mitochondrial function via the PI3K/Akt/eNOS signaling pathway, including mitochondrial dynamics and mitophagy, was investigated under a diabetic state and high glucose (HG) ambiance. To elucidate how the activation of MR provokes mitochondrial dysfunction in DT, human kidney proximal tubular epithelial (HK-2) cells were exposed to HG, and then mitochondrial dynamics, mitophagy, mitochondrial ROS (mitoROS), signaling molecules PI3K, Akt, Akt phosphorylation and eNOS were probed. The above molecules or proteins were also explored in the kidneys of diabetic and FIN-treated mice. FIN treatment reduced oxidative stress, mitochondrial fragmentation, and apoptosis while restoring the mitophagy via PI3K/Akt/eNOS signaling pathway in HK-2 cells exposed to HG ambiance and tubular cells of DM mice. These findings linked MR activation to mitochondrial dysfunction via PI3K/Akt/eNOS signaling pathway in DT and highlight a pivotal but previously undiscovered role of FIN in alleviating renal tubule injury for the treatment of DKD.
Topics: Humans; Mice; Animals; Proto-Oncogene Proteins c-akt; Mineralocorticoid Receptor Antagonists; Phosphatidylinositol 3-Kinases; Signal Transduction; Diabetic Nephropathies; Mitochondria; Diabetes Mellitus
PubMed: 37924663
DOI: 10.1016/j.redox.2023.102946 -
Nature Medicine Oct 2023Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute... (Randomized Controlled Trial)
Randomized Controlled Trial
Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l. The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively (P = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62-1.38], P = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 .
Topics: Female; Humans; Male; Acute Disease; Diuretics; Heart Failure; Natriuresis; Sodium; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 37640861
DOI: 10.1038/s41591-023-02532-z -
The American Journal of Cardiology Jul 2023Mineralocorticoid receptor antagonists (MRAs) are known to improve clinical outcomes in heart failure, particularly heart failure with reduced ejection fraction.... (Meta-Analysis)
Meta-Analysis Review
Mineralocorticoid receptor antagonists (MRAs) are known to improve clinical outcomes in heart failure, particularly heart failure with reduced ejection fraction. However, the effect of MRAs on the incidence of and recurrence of atrial fibrillation (AF) is not well established. Therefore, databases, such as PubMed, EMBASE, and Cochrane Central, were searched from inception to September 2021 for randomized controlled trials of MRAs with AF as an outcome. Risk ratios (RRs) with 95% confidence interval (CIs) were combined using the random-effects model. A total of 10 randomized controlled trials (n = 11,356) were included. Our pooled analysis demonstrates that MRAs reduce the risk of AF occurrence by 23% compared with the control therapy (RR 0.77, 95% CI 0.65 to 0.91, p = 0.003, I = 40%). Subgroup analysis demonstrated that MRAs reduced the risk of both new-onset AF (RR 0.84, 95% CI 0.61 to 1.16, p = 0.28, I = 43%) and recurrent AF (RR 0.73, 95% CI 0.59 to 0.90, p = 0.004, I = 26%) similarly; p interaction = 0.48. Our meta-analysis concludes that MRAs reduce the risk of development of AF overall, with consistent effects in new-onset and recurrent AF.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Atrial Fibrillation; Heart Failure; Incidence; Odds Ratio
PubMed: 37269781
DOI: 10.1016/j.amjcard.2023.04.038