A 58-year-old male patient with type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, coronary artery disease, and chronic kidney disease (CKD) presents to you for routine follow-up. He was hospitalized 1 year ago for an acute myocardial infarction (MI) and underwent revascularization of the right coronary artery with a drug-eluting stent. On physical exam, his heart rate is 62 bpm and blood pressure is 138/60 mmHg. There is no jugular venous distension, his lungs are clear to auscultation, and he has no peripheral edema. His laboratory evaluation includes an estimated glomerular filtration rate of 48 mL/min/1.73m2, low-density lipoprotein of 50 mg/dL, and hemoglobin A1c of 6.8%. Echocardiography demonstrates a left ventricular ejection fraction of 50%. He is currently on aspirin 81 mg daily, ticagrelor 90 mg twice daily, metoprolol succinate 100 mg daily, atorvastatin 80 mg daily, losartan 100 mg daily, and metformin 1 gm daily.
Based on the result of a large, randomized trial, which of the following additional therapies is likely to improve this patient's cardiac outcomes?
The correct answer is: C. Finerenone because the patient has T2DM and CKD.
Patients with CKD and T2DM are at a very high risk of cardiovascular morbidity and mortality. Evidence supports a pathophysiological role for overactivation of the mineralocorticoid receptor in cardiorenal diseases, including CKD and T2DM, through inflammation and fibrosis that lead to progressive kidney and cardiovascular dysfunction. Finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), has more potent anti-inflammatory and anti-fibrotic effects than steroidal MRAs and has a higher affinity to the heart than the kidney, thereby reducing the risk for hyperkalemia and adverse renal outcomes. The FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) trial investigated the effects of finerenone on cardiovascular and kidney outcomes in 5,734 patients with CKD and T2DM who were already treated with maximum acceptable renin-angiotensin system blockade.1
The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the estimated glomerular filtration rate from baseline, or death from renal causes. During a median follow-up of 2.6 years, a primary outcome event occurred in 17.8% in the finerenone group and 21.1% in the placebo group (hazard ratio 0.82; 95% confidence interval, 0.73-0.93; p = 0.001). The frequency of adverse events was similar in the 2 groups. A prespecified secondary analysis of the FIDELIO-DKD trial demonstrated that finerenone lowered the risk of cardiovascular events in patients with or without a history of cardiovascular disease without increasing the risk for treatment-emergent adverse events compared with placebo.2 Finerenone therapy was also associated with a reduced risk of new-onset atrial fibrillation or flutter.3 Finerenone is currently undergoing review by the US Food and Drug Administration.
Eplerenone and spironolactone, both steroidal MRAs, reduced the risk of all-cause and cardiovascular mortality and cardiovascular hospitalization risk in patients with HF with reduced ejection fraction.4 This patient has a left ventricular ejection fraction of 50%, making it uncertain if these MRAs will improve cardiovascular outcomes in this patient. Further, MRA therapy in the acute MI population without HF did not demonstrate any clear cardiovascular benefit (REMINDER [Impact Of Eplerenone On Cardiovascular Outcomes In Patients Post Myocardial Infarction] and ALBATROSS [Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion in improve Outcome and Survival at Six months follow-up] trials).4 Sacubitril/valsartan therapy demonstrated improved cardiovascular outcomes in patients with HF with reduced ejection (but not HF with preserved ejection) even in the presence of CKD and T2DM.5 Based on available data, it uncertain if this medication will improve cardiovascular outcomes in this patient.
Bakris GL, Agarwal R, Anker SD, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med 2020;383:2219-29.
Filippatos G, Anker SD, Agarwal R, et al. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes. Circulation 2021;143:540-52.
Filippatos G, Bakris GL, Pitt B, et al. Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes. J Am Coll Cardiol 2021;78:142-52.
Agarwal R, Kolkhof P, Bakris G, et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J 2021;42:152-61.
Yandrapalli S, Andries G, Biswas M, Khera S. Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives. Vasc Health Risk Manag 2017;13:369-82.