Author: Abdullah Al-Ajmi, PharmD Candidate, Skaggs School of Pharmacy and Pharmaceutical Sciences
Finerenone, which treats CKD, may also help to reduce cardiac failure in type 2.
Patients with type 2 diabetes (T2D) have an increased risk of cardiovascular disease (CVD). The risk is further increased by the presence of chronic kidney disease (CKD). CVD mortality in patients with T2D and CKD is significantly higher than in patients without CKD. Patients’ estimated glomerular filtration rate (eGFR) and albuminuria are considered predictors for CVD related mortality. For example, eGFR <60ml/min/1.73m2 has a two times higher risk of heart failure. Also, mild albuminuria is associated with a higher CVD risk. There are multiple risk factors that drive the risk of atherosclerotic cardiovascular disease (ASCVD), including hypertension (HTN), prior ASCVD event, metabolic factors, and inflammation. Activation of mineralocorticoid receptors (MR) can lead to an increase in cardiac and renal damage. The increased activation of MR is linked to increased aldosterone levels, which leads to resistant HTN, stroke, and heart failure. It is also linked to worsening CKD. Finerenone is a third-generation MR antagonist. It was reported to reduce cardiac failure and all-cause mortality and T2D or CKD patients in a phase 2 trial.
This study (Phase 3 trial) aims to explore further the effect of finerenone on reducing the CVD risk in patients with T2D and CKD.
The study was a randomized, placebo-controlled trial set in multiple countries. The study included patients who were 18 years or older with T2D. Patients had to have an elevated albumin-to-creatinine ratio mild (from 30 to less than 300mg/g) to severe (from 300 to less than 500mg/g). Also, they had to have an eGFR between 25 to less than 60ml/min/1.73m2. The study also included patients with diabetic retinopathy. Patients had to be on a maximum tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptors blocker (ARB) for at least one month. Potassium levels had to be below 4.8mEq/L. The study excluded patients with CKD that was not associated with T2D, uncontrolled HTN, unstable heart failure, renal transplant, or dialysis. Patients were randomized at a 1:1 ratio to receive finerenone 10-20mg orally once daily or identical placebo. The dose was determined based on the eGFR.
The primary outcome was defined as the first incidence of MI, stroke, heart failure-related hospitalization, or CVD mortality. Renal outcomes include long-term dialysis of at least three months, transplant, or eGFR below 15ml/min/1.73m2, eGFR reduced by ≥40% for a minimum of 30 days, or renal related mortality.
Around 5674 patients were included in the study. The average follow-up period was 2.6 years. Approximately 46% of patients in both groups had CVD at the beginning of the study. The overall baseline characteristics were similar between the groups. At baseline, patients with CVD were mostly older males and had been diagnosed with T2D for a longer duration. Other parameters such as A1C, BP, and eGFR were similar between the groups.
In terms of CV outcomes, patients on finerenone had significantly lower CVD events than placebo hazard ratio (HR)=0.86 (95% CI, 0.75-0.99, P=0.034). It was seen as a lower CVD mortality with finerenone (4.5%) than placebo (5.3%). The rate of nonfatal MI and heart failure-related hospitalization were lower in the finerenone group. However, the rate of stroke was higher in the finerenone group (3.2%) compared to placebo (3.1%), but it was not statistically significant HR=1.03 (95%, 0.76-1.38). These results were similar across all outcomes when patients were stratified based on having CVD at baseline. Furthermore, one month after stopping the study drug, the rate of CVD risk reduction was higher in patients who received finerenone. It was reduced by 24% in patients with prior CVD and 21% in patients without prior CVD.
The finerenone effect was significant in patients with prior CVD compared to placebo in terms of renal outcomes. In this patient population, the renal outcomes were reported in 15% of patients in the finerenone group compared to the 20% in the placebo group HR=0.7 (95% CI, 0.58-0.84). In patients without prior CVD, finerenone had a slightly lower rate of renal events (19.9%) compared to placebo (21.6%) HR=0.94 (95% CI, 0.81-1.10).
In terms of the safety outcomes, adverse drug events (ADEs) were more prevalent in the finerenone group regardless of the patients‘ CVD history. Finerenone was mostly associated with hyperkalemia.
Overall, finerenone showed benefit in reducing CV risk compared to placebo in patients with T2D regardless of CVD history. The study did not assess the patient‘s CVD history at the screening phase; instead, it relied on medical record data, which may have led to incomplete medical history.
- Finerenone improves CVD outcomes in patients with T2D and CKD.
- Finerenone reduces CKD progression in patients with T2D and a history of CVD.
- Hyperkalemia is one of the common side effects of finerenone.
Filippatos, Gerasimos et al. “Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes.“ Circulation, 10.1161/CIRCULATIONAHA.120.051898. November 16, 2020, doi:10.1161/CIRCULATIONAHA.120.051898. Available from: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.051898
Haller, Hermann et al. “Finerenone: a New Mineralocorticoid Receptor Antagonist Without Hyperkalemia: an Opportunity in Patients with CKD?.“ Current hypertension reports vol. 18,5 (2016): 41. doi:10.1007/s11906-016-0649-2. Available from: https://link.springer.com/article/10.1007/s11906-016-0649-2
Abdullah Al-Ajmi, PharmD Candidate, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences