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.