Efficacy and safety of finerenone in patients with cardio-kidney-metabolic syndrome and history of cancer: the FINE-HEART pooled analysis
M Ruppert, M Vaduganathan, B L Claggett, A S Desai, P S Jhund, M S Anker, C S P Lam, M Senni, A A Voors, F Zannad, R Agarwal, J J V Mcmurray, S D Solomon, S D Anker, G FilippatosAbstract
Aims
Individuals with cardio-kidney-metabolic (CKM) comorbidities are more likely to develop cancer, and comorbid cancer portends worse prognosis. The non-steroidal mineralocorticoid receptor antagonist finerenone has been shown to provide benefit in broad cohort of patients with CKM conditions. However, it remains unknown whether these benefits persist in patients with a history of cancer.
Purpose
To evaluate the effects of finerenone on clinical outcomes among patients with CKM conditions and comorbid cancer, and on cancer-related mortality and the development of de novo malignancies.
Methods
This was a post hoc analysis of FINE-HEART, a participant-level pooled analysis of the FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF trials. Participants with life-limiting malignancies were excluded from all trials. Baseline cancer status was derived from medical history, while incident cancer was identified from adverse event reports. The risks of all-cause and cardiovascular death, all-cause and HF-related hospitalization, a composite kidney outcome, and new-onset atrial fibrillation, according to baseline cancer status and randomization to finerenone, were assessed using Cox proportional hazards models stratified by region and trial. The effects of finerenone on cancer-related death and de novo cancer development were further evaluated using competing risk analyses.
Results
Among the 18,991 participants, 1,389 (7.3%) had a history of cancer at baseline. The most common types of neoplasms were gastrointestinal, male reproductive, renal and urinary tract and hematopoietic. Patients with history of cancer were older, had lower eGFR, urinary albumin-to-creatinine ratio, serum potassium, hemoglobin A1c, higher waist circumference, and more frequently diagnosed with atrial fibrillation. A history of cancer was associated with higher risks of all-cause mortality and all-cause hospitalization. Over the median follow-up of 2.9 years, finerenone reduced the risk of all-cause mortality, all-cause, and HF-related hospitalization, the composite kidney outcome, and new-onset atrial fibrillation, consistently in individuals with and without a history of cancer (Figure 1). Adverse events were more commonly reported in patients with a history of cancer, but the safety profile of finerenone appeared consistent irrespective of cancer history (Table 1). The subdistribution hazard ratio was 0.81, 95% CI 0.64–1.03 for the treatment effects on cancer death and was 0.92, 95% CI 0.79–1.06 for the incidence of de novo cancer, when non-cancer related death and all-cause death, respectively, were considered as competing risks.
Conclusions
History of cancer, while being associated with heightened risks of mortality and morbidity, did not appear to alter the efficacy and safety of finerenone in patients with CKM conditions. These data suggest that a history of cancer alone, if not in advanced stages, should not deter implementation of risk-lowering therapies to improve CKM health.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.