Introduction:
Heart failure (HF) is not a solitary pathological condition but rather a
clinical syndrome comprising of cardinal symptoms (such as shortness of
breath, ankle edema, and fatigue) that may be backed by signs (such as
high jugular venous pressure, pulmonary crackles, and peripheral edema).
It is caused by structural or functional abnormalities of the heart that
results in increased intraventricular pressures and low cardiac output
at rest or during activity.[1] The prevalence of
heart failure (HF) is rising and affecting at least 26 million
individuals worldwide. 1–2 % of the general population is diagnosed
with HF, and 5–10% of those aged 65 and older have the
diagnosis.[2] According to the American College of
Cardiology/American Heart Association Joint Committee Clinical Practice
Guidelines, left ventricular ejection fraction (LVEF) is important in
the categorization of patients with HF because of differences in
survival rate and response to therapeutic interventions and because most
clinical studies select patients based on ejection fraction (EF). Heart
failure with reduced ejection fraction (HFrEF) is defined as LVEF40%.
In contrast, HF with preserved EF (HFpEF) represents at least 50% of
the HF cohort, and its prevalence is rising.[3] HF, type 2 diabetes
mellitus (T2DM), and chronic kidney disease (CKD) are significant
pandemics of the 21st century.[1] It is now
well-known that cardiovascular disease (CVD) is the major cause of this
comorbidity and contributes to approximately 60–75 % of fatalities
among people with diabetes. Diabetes increases the risk of
cardiovascular disease by two to four, and its presence in patients with
cardiovascular disease is one of the strongest predictors of bad
clinical outcomes.[4] Despite current
interventions, patients with CKD and T2DM have substantial residual
cardiorenal morbidity and mortality. The risks of renal failure
advancement and cardiovascular problems rise with the intensity and
stage of CKD. In contrast to individuals with advanced kidney disease,
who are more likely to progress to dialysis, patients with better
preserved estimated glomerular filtration rate (eGFR) have a higher
lifetime risk of the cardiovascular burden of diseases, such as heart
failure, myocardial infarction (MI), stroke, or cardiovascular
death.[5]
Diabetes is the major cause of chronic kidney disease (CKD), which
affects 30% to 40% of individuals with diabetes. Diabetes affects 537
million people worldwide, or one in every ten, and the figure is
anticipated to rise to 783 million by 2040.[7] As
a result, diabetic kidney disease (DKD) is one of the most devastating
complications of diabetes and the leading cause of kidney failure.
Chronic kidney disease (CKD) caused by diabetes mellitus is currently
diagnosed as diabetic nephropathy, which commences with microalbuminuria
and then a steady decline in renal function. It is diagnosed
pathologically by distinctive disease processes, such as increased
mesangial substrate, nodular lesions, and tubulointerstitial
fibrosis.[6] Various interdisciplinary therapies,
including ACE inhibitors, SGLT2 inhibitors, and mineralocorticoid
receptor antagonists, have been proposed based on critical
pathophysiological pathways. Some of them are effective in illnesses
such as diabetes and chronic kidney disease. These therapies impact not
only diabetics and people with the chronic renal disease but also the
physiology of the heart.[6] Increasing evidence
points to pathological overactivation of the mineralocorticoid receptor
(MR) as a significant predictor of CKD progression and associated
morbidity and death. Furthermore, recent research indicates that
overactivation of the mineralocorticoid receptor (MR) causes
inflammation and fibrosis in the heart, kidneys, and vasculature,
accelerating the course of CKD and cardiovascular disease. Therefore,
several studies have indicated that inhibiting the mineralocorticoid
receptor pharmacologically lowers albuminuria, kidney fibrosis,
glomerular lesions, and inflammation in preclinical models of CKD in
T2D; favorable cardiovascular benefits have also been noted. Despite
clinical studies demonstrating that mineralocorticoid receptor
antagonists (MRAs) have an anti-albuminuric impact in diabetic kidney
disease, the risk of hyperkalemia accompanied by their usage has
restricted their use and evaluation for severe renal and cardiovascular
outcomes.[9] Nevertheless, side effects such as
hyperkalemia are avoided with concomitant other drugs; hence MR
antagonism is being investigated as a novel therapy regimen to delay the
progression of CKD.[8]
Finerenone is a revolutionary, selective, nonsteroidal MR antagonist
(MRA) with anti-inflammatory and anti-fibrotic properties in
experimental renal and cardiovascular diseases
trials.[5] According to studies, the incidence of
death from cardiovascular causes, nonfatal myocardial infarction,
nonfatal stroke, or hospitalization for heart failure (the primary
composite outcome) is dramatically reduced in finerenone-treated
individuals. Additionally, severe and adverse events associated with
pneumonia are less frequent with finerenone compared to
placebo.[10]
Meta-analysis is a statistical, systematic, epidemiological research
strategy used to critically assess previous research findings to
conclude that body of research. The results of a meta-analysis may
provide a more precise estimate of the effect of a treatment or risk
factor for disease, or other outcomes, than any individual study
contributing to the pooled analysis. Because few randomized controlled
trials have been performed to examine the efficacy and safety profile of
finerenone on chronic kidney disease and cardiovascular outcomes in Type
2 Diabetes, most of the studies have yielded contradictory results due
to various adverse effect profiles. Therefore, we carried out a
comprehensive systematic review and meta-analysis to determine the
precise role of finerenone in patients with CKD and Type 2 diabetes. To
the best of our knowledge, this is the first meta-analysis that compares
the effects of finerenone therapy versus placebo in patients with CKD
and T2D.