Background: Heart failure is a chronic disease linked with significant morbidity and mortality, and uncontrolled resting heart rate is a risk factor for adverse outcomes. This systematic literature review aimed to assess the efficacy, safety, and patient-reported outcomes (PROs) of ivabradine in patients with heart failure (HF) with reduced ejection fraction (HFrEF) in randomized controlled trials (RCTs) and observational studies.

Finerenone (FIN: an oral, nonsteroidal mineralocorticoid receptor antagonist) and canagliflozin (CAN: a sodium-glucose cotransporter 2 inhibitor) demonstrated cardiorenal efficacy in patients with chronic kidney disease and type 2 diabetes on top of renin–angiotensin system blockade in phase III placebo-controlled studies (FIDELIO-DKD [NCT02540993] for FIN; CREDENCE [NCT02065791] for CAN) [ 3, 2]. In the absence of head-to-head studies, we assessed FIN and CAN in this patient population while appropriately accounting for meaningful differences between the trials. We performed an anchored matching-adjusted indirect comparison (MAIC), with placebo (PBO) as a common comparator, to generate measures of efficacy and safety while accounting for differences between the two study populations [ 3]. Individual patient-level data from FIDELIO-DKD and published data from CREDENCE were used [ 1,[ 2]. Weights were calculated and assigned to each patient in FIDELIO-DKD so the weighted population of FIDELIO-DKD matched that of CREDENCE for selected baseline characteristics, e.g. mean estimated glomerular filtration rate (eGFR; 44.3 and 56.2 mL/min/1.73 m² in FIDELIO-DKD and CREDENCE, respectively). Weights were obtained from a logistic regression model of the odds of enrolment in CREDENCE and FIDELIO-DKD for baseline characteristics believed to be effect modifiers. Hazard ratios (HRs) with 95% confidence intervals (CIs) comparing FIN and PBO for time-to-event endpoints were estimated based on the weighted population of FIDELIO-DKD. HRs with 95% CIs comparing FIN and CAN were then calculated from results of the previous step and published data from CREDENCE [ 2]. This analysis evaluated the cardiorenal composite endpoint from CREDENCE (kidney failure [dialysis, transplantation or sustained eGFR < 15 mL/min/1.73 m²), a doubling of serum creatinine level or death from kidney or cardiovascular disease) [ 2] and hyperkalaemia. A sensitivity analysis that matched patients based on their history of heart failure was performed. Calculation of the weights for the FIDELIO-DKD population (N = 5674) resulted in an effective sample size of 1288 for the pseudo-population formed by the weighting to compare with the CREDENCE population (N = 4401). For the cardiorenal composite endpoint, the HR (95% CI) for FIN and PBO based on reweighted FIDELIO-DKD data was 0.72 (0.59–0.90) and the MAIC-based HR (95% CI) for FIN and CAN was 1.03 (0.79–1.35) (P = 0.802). For hyperkalaemia, the MAIC-based HR (95% CI) for FIN and CAN was 2.25 (1.67–3.03) (P < 0.001). Similar efficacy and safety results were demonstrated in the sensitivity analysis. The MAIC for FIDELIO-DKD and CREDENCE enabled more robust assessment of FIN and CAN when a similar patient population was considered. There was no evidence of a significant difference between FIN and CAN in the cardiorenal composite endpoint as assessed in CREDENCE. These results are consistent with a recent analysis using a different payer-accepted method that also accounted for differences between the FIDELIO-DKD and CREDENCE inclusion criteria and endpoints [ 3, 4].

This study aimed to close an evidence gap concerning the relative efficacy of finerenone versus SGLT2is in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Canagliflozin was selected as a proxy for the SGLT2i class. Patient-level data of two randomized controlled trials (RCTs) of finerenone (FIDELIO-DKD and FIGARO-DKD) were used alongside aggregated data from CREDENCE, an RCT of canagliflozin. To account for meaningful between-study heterogeneity between each finerenone trial and CREDENCE, a matching-adjusted indirect comparison of a range of efficacy outcomes was undertaken for each finerenone study versus CREDENCE. These results were meta-analyzed, enabling the estimation of the relative effects of finerenone against canagliflozin. For the cardiorenal composite endpoint, the hazard ratio (HR) comparing finerenone to canagliflozin was 1.07 (95% CI: 0.83 to 1.36). The corresponding HRs for all-cause mortality, end-stage kidney disease and cardiovascular death were 0.99 (95% CI: 0.73 to 1.34), 1.03 (95% CI: 0.68 to 1.55) and 0.94 (95% CI: 0.64 to 1.37), respectively. The absence of statistically significant differences was consistent throughout the main analysis and a range of sensitivity analyses. Based on this study, using a large sample of data and adjusted for meaningful differences between the baseline characteristics of the included RCTs, there was no statistically significant evidence indicating a difference in the efficacy of finerenone compared to canagliflozin in the treatment of CKD in patients with T2D.