Latest news with #finerenone
Medscape
5 days ago
- Health
- Medscape
Combination Therapy Offers CONFIDENCE to CKD+T2D Patients
VIENNA — Combining the SGLT2 inhibitor empagliflozin with finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), markedly and durably reduced albuminuria in patients with both chronic kidney disease (CKD) and type 2 diabetes (T2D), the CONFIDENCE trial showed in findings that offer hope of a long-term improvement in outcomes. In the trial, 70% of patients on both therapies achieved the American Diabetes Association recommended urinary albumin-to-creatinine ratio (UACR) reduction target of > 30%. 'Since UACR is a key mediator of kidney and cardiovascular outcomes, these results are highly relevant for clinical decision-making,' said lead researcher Rajiv Agarwal, MD, MS, professor emeritus of medicine, Indiana University School of Medicine, Indianapolis. The results were presented here at the 62nd European Renal Association (ERA) Congress 2025 on June 5 and sparked enthusiastic applause from the audience. The findings were simultaneously published in The New England Journal of Medicine. Agarwal, who shared the podium with three of his co-investigators to present the study, added that this was in keeping with 'other chronic conditions like heart failure or hypertension,' in that 'we're moving away from the traditional stepwise approach toward upfront combination therapy.' Session co-chair Mustafa Arici, MD, professor of medicine (nephrology), Hacettepe University, Ankara, Turkey, described the results as 'remarkable.' He told Medscape Medical News , 'For protecting the kidneys of type 2 diabetes patients, it looks like we now have the data to start an SGLT2 inhibitor plus an MRA in combination from the first day, because the data is very solid.' Arici noted, however, that the study did not include clinical endpoints and 'people usually would like to hear solid outcomes. We would like to see whether the number of dialyses decreased or the mortality decreased.' But — as the presenters themselves pointed out — the numbers required to show a clinical benefit are too large to feasibly conduct a trial, he said. 'Obviously there is a surrogate outcome here, which is the UACR,' said Arici. "And at the moment, we have data from 800 people with a good amount of follow up and with no safety signal, which is important." Implementing and Combining Additional Drugs Co-investigator of the CONFIDENCE study, Peter Rossing, MD, PhD, clinical professor, Steno Diabetes Center, Copenhagen, Denmark, noted that, in terms of treatment, the standard of care in patients with CKD and T2D is based on four pillars, with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) joined in recent years by SGLT2 inhibitors, MRAs, and GLP-1 receptor agonists. 'However, we do not know really how to implement these additional drugs and how to combine them,' Rossing said. Clues have come from combination trials in hypertension and heart failure with reduced ejection fraction, which led to the evolution of guideline recommendations and the mantra that, when it comes to using multiple drugs, it is better to give 'some of all, instead of all of some.' A recent analysis also suggested that steroidal MRAs and SGLT2 inhibitors may have additive effects in reducing UACR, far more than either drug alone, although only 32 patients in the study had both CKD and T2D. In the current trial, patients were enrolled if they had: a UACR of ≥ 100 – < 5000 mg/g; an estimated glomerular filtration rate (eGFR) of 30-90 mL/min/1.73 m2; T2D with an A1c < 11%; and were receiving clinically maximally tolerated doses of ACE inhibitors/ARBs for > 1 month. The participants were randomly assigned to one of three groups: simultaneous finerenone plus empagliflozin; finerenone plus placebo; or empagliflozin plus placebo. Patients were treated for 180 days, with clinical visits on days 14, 30, and 90, and then went through a washout period through to day 210. Choosing a composite kidney endpoint for the primary efficacy analysis would have required 41,000 patients to be enrolled into the trial, explained co-investigator Hiddo J.L. Heerspink, PhD, Department of Clinical Pharmacology, University Medical Center, Groningen, Netherlands. Instead, the researchers opted for the more feasible primary endpoint of relative change in UACR from baseline to day 180, as previous studies have shown that short-term UACR changes are associated with kidney protection in the long term. In all, 818 patients were randomly assigned from 143 sites in 14 countries, of whom 269 ended up receiving the combination therapy, 264 had finerenone monotherapy, and 267 were treated with empagliflozin alone. The mean age of the patients was 67 years, and 75% were male. Forty-six percent were Asian and 44% were White. Turning to the efficacy analysis, Agarwal asked the audience to vote on the percentage reduction in UACR that they expected the combination therapy would achieve. The most common answer, chosen by 37.7% of voters, was 30%-40%. Agarwal then showed that, in fact, combining finerenone with empagliflozin achieved a 52% reduction in UACR over baseline, 32% greater than that seen with empagliflozin alone, and 29% greater than that seen with finerenone monotherapy. 'It's great to see some positive trial results,' he added, in response to the audience's acclamation. In addition, only 52% of patients treated with either drug alone reached a > 30% reduction in UACR at day 180 compared to the 70% of patients treated with the combination. In addition, a total of 64% of patients treated with the combination achieved a > 40% reduction in UACR, and 55% reached a > 50% reduction. In both cases, the proportions of patients reaching the target with monotherapy were approximately 20% lower. The benefit in terms of serum potassium levels was also notable, as there was a 17.7% reduction in the incidence of treatment-emergent hyperkalemia, defined as serum levels > 5.5 mmol/L, with combination therapy vs finerenone monotherapy. Agarwal also noted that there was a low incidence of hypotension with combination therapy, with just three cases (1.1%), and a low incidence of acute kidney injury, at five cases (1.9%). There was an initial decline in eGFR, which was described as 'predictable' and largely reversible after drug withdrawal. Crucially, the researchers also showed that during the washout period, UACR levels returned to almost those seen at baseline. This pattern was also observed with the marked improvements in both serum potassium and blood pressure levels that were seen with finerenone plus empagliflozin, which were again greater than those achieved with either monotherapy. After the data were presented, study co-investigator Johannes F.E. Mann, MD, head, KfH Kidney Center, Munich, Germany, sought to explain the implications of the findings by pointing to a recent mediation analysis of pooled data from two phase 3, double-blind trials of finerenone. This revealed that reductions in UACR over the first 4 months of treatment explained 84% of the later reductions in kidney progression and 37% of the reductions in cardiovascular outcomes, suggesting that the findings from CONFIDENCE may well translate into later improvements in clinical endpoints. Muthiah Vaduganathan, MD, MPH, from the Department of Cardiovascular Medicine at Brigham and Women's Hospital, Boston, welcomed the findings. Commenting on X (formerly Twitter), he said that the simultaneous initiation of the combination therapy 'safely and rapidly delivers' in patients with both CKD and T2D. 'A new age of combination therapies has arrived.' The study was funded by Bayer. Agarwal declares relationships with Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, Novartis, UpToDate, Wolters Kluwer, Chinook, and Vertex. Rossing declares relationships with AstraZeneca, Bayer, Novo Nordisk, Abbott, Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Sanofi, Daiichi Sankyo, and Lexicon Pharma. Heerspink declares relationships with Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, BioCity, Dimerix, Eli Lilly, Janssen, Novartis, Novo Nordisk, Roche, and Travere Therapeutics. Mann declares relationships with Novo Nordisk, the European Union, Bayer, AstraZeneca, Bayer, Novartis, UpToDate, Cytel, IQVIA, Parexel, WCG, and Sanofi.
Medscape
5 days ago
- Business
- Medscape
New Hyperkalemia Risk Model for CKD and Diabetes
A new risk model may help identify which patients with chronic kidney disease (CKD) and diabetes are more likely to develop hyperkalemia, granting physicians more confidence in prescribing medications like finerenone. However, researchers caution that further validation is needed. The model is based on pooled data from two phase 3 trials of finerenone: FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease). The combined dataset, known as FIDELITY, includes 6355 patients in the placebo groups. Researchers used this dataset to develop the risk score, identifying seven factors independently associated with the primary outcome of new onset of hyperkalemia (incident serum potassium level > 5.5 mmol/L): Serum potassium > 4.5 mmol/L Prior history of hyperkalemia No use of sodium-glucose co-transporter 2 inhibitor Urine albumin-to-creatinine ratio > 1000 mg/g Hemoglobin < 12 g/dL No use of thiazide-type diuretics Estimated glomerular filtration rate < 45 mL/min/1.73 m2 The model was subsequently validated using data from the finerenone groups in FIDELITY. In their paper, published online in the European Heart Journal , João Pedro Ferreira, MD, PhD, of the Cardiovascular Research and Development Center at the University of Porto, Porto, Portugal, and coauthors noted that the model could be used to reduce the risk for hyperkalemia among high-risk patients receiving finerenone. 'This could include tailoring of individualized treatment and follow-up strategies (eg, frequency of visits and serum potassium assessments, and use of potassium binders), thus optimizing patient management and potentially improving outcomes,' they noted. Welcome Results, Validation Required CKD, which affects more than 800 million people worldwide, is a common complication of diabetes. An estimated 15%-40% of people with CKD in the setting of diabetes may have hyperkalemia, noted Bernard G. Jaar, MD, MPH, clinical director for Nephrology at Johns Hopkins School of Medicine, Baltimore, who was not involved in the study. In an email exchange with Medscape Medical News , Jaar described the study as 'welcome and much needed.' He noted that hyperkalemia poses a challenge for clinicians, as many medications required for optimal care in CKD — including renin-angiotensin-aldosterone system (RAAS) blockade agents and finerenone — can raise serum potassium. 'This is a true barrier to care,' Jaar wrote. 'Clinicians are worried about the potential complications associated with hyperkalemia, such as arrhythmias and even death.' Jaar noted that the FIDELITY analysis has several strengths, including its large sample size of patients with varying stages of CKD and degrees of proteinuria, and a risk score model that incorporated readily available clinical variables. He added that it reports a stepwise increase in hyperkalemia risk across risk score tertiles in both placebo and finerenone groups, even though all patients were already on a maximally tolerated RAAS blockade agent. However, he questioned the study's generalizability, given that it excluded patients if their serum potassium was > 4.8 mmol/L. 'This risk model in predicting hyperkalemia needs to be validated in other populations where diet may be different,' Jaar wrote. 'Also, this needs to be validated in at-risk populations during real-life experience and not only in patients enrolled in clinical trials, who are typically highly motivated and selected.' Future Applications Rajiv Agarwal, MD, MS, professor emeritus of medicine at Indiana University and a lead researcher in the finerenone clinical studies, echoed the need for further validation of this tool. Although not involved with the development of the risk model, Agarwal was an author on key publications from the FIGARO-DKD, FIDELIO-DKD, and FIDELITY studies. Agarwal suggested that this model's approach could be applied to other therapies, including aldosterone synthase inhibitors in a similar population with CKD. He also noted the importance of incorporating validated risk models for hyperkalemia into electronic medical records or apps, particularly in countries with limited access to care, like China and India. This would allow more nuanced approaches for following up patients taking drugs with established hyperkalemia risk. 'If the patient cannot come after a month, can I make a clinical judgment and say, 'Okay, if you came back after 3 months, your risk of hyperkalemia is low enough that I'm willing to take that risk,'' he said. 'Or if the risk of hyperkalemia is high, you can tell the patient who can't come back in 30 days, 'I don't think I want to prescribe this drug for you'.' The work on the risk model was supported by Bayer, which also funded the FIDELIO-DKD and FIGARO-DKD studies and pooled analysis. The study's authors included Bayer employees. Other financial relationships of the authors included research support, consulting and other fees from companies including: Abbott Vascular, Amgen, Astellas, AstraZeneca, Bayer, BioVentrix, Boehringer Ingelheim, Brahms, Brainstorm Medical, Cardiac Dimensions, Cardior, Cereno Scientific, CSL Vifor, CVRx, Edwards, Eli Lilly, G3 Pharmaceuticals, Gilead, GSK, Impulse Dynamics, Janssen, KBP Biosciences, Mundipharma, Novartis, Novo Nordisk, Occlutech, PhaseBio, Proton Intel, Respicardia, Sanofi, Sarfez, scPharmaceuticals, Servier, SQ Innovation, Tricida, Vectorious, Vifor International, and V-Wave. Agarwal had received support from Bayer. He also had received consulting fees and other support from Boehringer Ingelheim, Novartis, Akebia, Intercept Pharma, Alnylam, and Vertex. Jaar reported no relevant financial disclosures.
