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Cureus Jul 2023The purpose of this study is to assess the safety and efficacy of finerenone therapy in type 2 diabetes mellitus (T2DM) patients with cardiovascular and chronic renal... (Review)
Review
A Systematic Review and Meta-Analysis on the Efficacy and Safety of Finerenone Therapy in Patients with Cardiovascular and Chronic Kidney Diseases in Type 2 Diabetes Mellitus.
The purpose of this study is to assess the safety and efficacy of finerenone therapy in type 2 diabetes mellitus (T2DM) patients with cardiovascular and chronic renal diseases. This meta-analysis assesses the efficacy and safety of finerenone in the treatment of diabetic kidney disease (DKD). A comprehensive search of PubMed, Embase, and Google Scholar databases was performed to identify relevant randomized controlled trials (RCTs). To quantify the effects of finerenone, the analysis included the estimation of aggregated mean differences (MDs) and relative risks (RRs), as well as 95% confidence intervals (CIs). This meta-analysis included seven double-blind trials with patients suffering from chronic kidney disease (CKD) and T2D. Participants received finerenone or a placebo was assigned at random. The primary efficacy outcomes were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, kidney failure, a sustained 57% decrease in the estimated glomerular filtration rate from baseline over four weeks, or renal death. Among the 39,995 patients included in the analysis, finerenone treatment was associated with a lower risk of cardiovascular and renal-related mortality compared to placebo (RR = 0.86 (0.80, 0.93), p = 0.0002; I-squared statistic (I ) = 0%) and (RR = 0.56 (0.17, 1.82), p = 0.34; I= 0%). In addition, finerenone treatment was associated with a marginally reduced risk of serious adverse events (RR = 0.95 (0.92, 0.97), p = 0.0001; I= 0%), although no significant difference in the overall risk of adverse events was observed between the two groups (RR = 1.00 (0.99, 1.01), p = 0.56; I= 0%). This study's findings suggest that finerenone administration can reduce the risk of end-stage kidney disease, renal failure, cardiovascular mortality, and hospitalization. Patients with both T2DM and CKD are therefore advised to consider finerenone therapy.
PubMed: 37575756
DOI: 10.7759/cureus.41746 -
Hellenic Journal of Cardiology : HJC =... 2023Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is... (Review)
Review
Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is an essential protein for maintaining muscle integrity. The lack of dystrophin plays a pathophysiological role in the development of dilated cardiomyopathy in Duchenne muscular dystrophy. Currently, no consensus exists on specific pharmacological therapy guidelines for these patients; however, it centers around the guidelines for heart failure management. This systematic review investigated 12 randomized control trials dating back to 2005 in the pharmacotherapy of patients with dilated cardiomyopathy Duchenne muscular dystrophy. This review specifically included angiotensin-converting enzyme inhibitors, aldosterone receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Despite their limitations, these studies have shown promising effects in improving the overall heart function and prognosis in patients with this condition. However, to attain higher statistical significance, future studies should investigate larger populations and for longer periods.
Topics: Humans; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne; Dystrophin; Angiotensin-Converting Enzyme Inhibitors; Adrenergic beta-Antagonists
PubMed: 37406964
DOI: 10.1016/j.hjc.2023.06.007 -
Nephrology, Dialysis, Transplantation :... Oct 2023Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis),... (Meta-Analysis)
Meta-Analysis
The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS
This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.
RESULTS
There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67).
CONCLUSION
Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.
Topics: Adult; Humans; Renin-Angiotensin System; Diabetic Nephropathies; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Acute Kidney Injury; Diabetes Mellitus
PubMed: 37309038
DOI: 10.1093/ndt/gfad101