: This review provides a comprehensive overview of heart failure with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF), including its definition, diagnosis, and epidemiology; clinical, humanistic, and economic burdens; current pharmacologic landscape in key pharmaceutical markets; and unmet needs to identify key knowledge gaps. We conducted a targeted literature review in electronic databases and prioritized articles with valuable insights into HFmrEF/HFpEF. Overall, 27 randomized controlled trials (RCTs), 66 real-world evidence studies, 18 clinical practice guidelines, and 25 additional publications were included. Although recent heart failure (HF) guidelines set left ventricular ejection fraction thresholds to differentiate categories, characterization and diagnosis criteria vary because of the incomplete disease understanding. Recent epidemiological data are limited and diverse. Approximately 50% of symptomatic HF patients have HFpEF, more common than HFmrEF. Prevalence varies with country because of differing definitions and study characteristics, making prevalence interpretation challenging. HFmrEF/HFpEF has considerable mortality risk, and the mortality rate varies with study and patient characteristics and treatments. HFmrEF/HFpEF is associated with considerable morbidity, poor patient outcomes, and common comorbidities. Patients require frequent hospitalizations; therefore, early intervention is crucial to prevent disease burden. Recent RCTs show promising results like risk reduction of composite cardiovascular death or HF hospitalization. Costs data are scarce, but the economic burden is increasing. Despite new drugs, unmet medical needs requiring new treatments remain. Thus, HFmrEF/HFpEF is a growing global healthcare concern. With improving yet incomplete understanding of this disease and its promising treatments, further research is required for better patient outcomes.

Background: Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria. Objective: We conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients. Results: A total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting. Conclusions: Despite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban versus apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose as the 20-mg dose has already been evaluated. Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15 mg twice daily for three weeks, followed by 20 mg once daily for six months, then extended prevention with 10 mg once daily) or apixaban (10 mg twice daily for one week, followed by 5 mg twice daily for six months, then extended prevention with 2.5 mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0–6 months) and an extended prevention phase (6–18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature. Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban. Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data. Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.

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.

This study aimed to validate the health economic model for finerenone in the treatment of patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≥40% in the United Kingdom. A Markov model informed by the pivotal FINEARTS-HF trial compared finerenone + standard of care (SoC) to SoC alone. Cross-validation was performed on the results (life years [LYs] and quality adjusted life years [QALYs]) for the SoC arm against three models in HF with LVEF >40%. External validation compared cardiovascular (CV) mortality and the number of total HF events (hospitalisation for heart failure [HFF] and urgent heart failure visit [UHFV]) against FINEARTS-HF. The model estimated similar discounted outcomes to other models in HF (6.47 vs. 6.63–7.91 LYs and 4.78 vs. 4.63–5.27 QALYs). CV deaths (22 vs. 27) and UHFV events (60 vs. 61) avoided with finerenone were similar between the model and FINEARTS-HF. The broad estimated range of avoided HHF events (205–303 vs. 219 in FINEARTS-HF) was largely driven by baseline patient age. This comprehensive validation exercise demonstrated that the finerenone model accurately estimated observed clinical data and was well aligned in its projections with previous models assessing similar populations.