On August 30, 2021, during the European Society of Cardiology (ESC) Congress 2021, Bayer hosted a global media briefing titled “Exploring the Path to Treatment for Heart Failure and Chronic Kidney Disease Complicated by Diabetes,” highlighting the novel-mechanism product “vericiguat” in the field of heart failure, along with strategies to help patients with chronic kidney disease and diabetes reduce their risks of renal and cardiovascular diseases.
Dr. Richard Nkulikiyinka, Head of Clinical Research for the Cardiovascular and Nephrology Therapeutic Areas at Bayer Pharmaceuticals Division, stated: Cardiovascular disease remains the leading cause of death globally, accounting for approximately 31% of all deaths worldwide. Although primarily a circulatory system disorder, compromised blood supply can adversely affect various organs throughout the body to varying degrees. This is why Bayer, with its longstanding expertise in cardiovascular medicine, recently introduced finerenone for patients with chronic kidney disease and type 2 diabetes. This therapy slows the progression of kidney disease in this patient population and reduces cardiovascular risk, enabling us to expand from a cardiovascular foundation into related therapeutic areas. Meanwhile, Bayer continues to advance its research in cardiovascular diseases. The heart failure treatment drug 「vericiguat」 has been successively approved in the United States, Europe, and Japan, and is expected to receive approval in China soon. The product pipeline also encompasses other investigational heart failure therapies. In the anticoagulation field, building upon our flagship drug Xarelto, our R&D efforts continue to expand toward targeting Coagulation Factor XI, which is currently in the clinical development stage.
Professor Javed Butler, Director of the Department of Pharmacy at the University of Mississippi Medical Center, shared three clinical cases from the frontline of heart failure management to illustrate the appropriate patient population for 「Vericiguat」 in clinical practice. For example, one male patient had been diagnosed with heart failure for two years, presenting with dyspnea and an ejection fraction of 35%. Given that a normal ejection fraction should typically be at least 50%, this patient's cardiac function was clearly suboptimal. Although he received treatment in both the emergency department and outpatient settings without experiencing a myocardial infarction, his ejection fraction remained unchanged. How should such cases be managed? What further therapeutic interventions can be offered?
According to Professor Javed, this situation is not uncommon in clinical practice; even with current treatments, some patients still require hospital readmission due to exacerbation events.
At this ESC Congress, “vericiguat” was incorporated into the updated heart failure guidelines. The drug has already been approved in the United States and other countries, with its approval based on the results of the Phase III VICTORIA trial:
Compared with placebo, vericiguat demonstrated superiority in the primary composite efficacy endpoint. The VICTORIA trial, a contemporary clinical study specifically targeting symptomatic chronic heart failure patients (ejection fraction <45%) who have experienced worsening events, has yielded positive results. This study evaluated the efficacy of vericiguat in combination with existing heart failure therapies. Compared with other recent heart failure trials, the annualized event rate for the primary composite endpoint of cardiovascular death or heart failure hospitalization in the placebo group was twice as high, and baseline NT-proBNP levels were also twofold higher, indicating that patients enrolled in the VICTORIA trial faced a higher risk of hospitalization or death compared to those in other recent heart failure studies.
Once-daily vericiguat, in combination with standard heart failure therapy, significantly reduced the composite endpoint of cardiovascular death and heart failure hospitalization in patients with symptomatic chronic heart failure (ejection fraction <45%) and a history of worsening events, with a hazard ratio of 0.9 (95% CI 0.82–0.98; p = 0.019) and an absolute risk reduction of 4.2 per 100 patient-years. Based on this absolute risk reduction, the number needed to treat (NNT) with vericiguat per year to prevent one primary event was approximately 24.
As the principal investigator of the Phase III FIDELIO-DKD and FIGARO-DKD clinical trials, Professor Gerasimos Filippatos from the National and Kapodistrian University of Athens, Greece, highlighted at the conference the role of finerenone in reducing the risk of cardiovascular events and slowing kidney disease progression in patients with chronic kidney disease (CKD) and type 2 diabetes. He particularly emphasized the critical importance of mitigating cardiovascular risk in patients with diabetes and CKD. Even with current therapeutic regimens, patients remain at a high risk of kidney failure and cardiovascular events. Data analysis underscores the importance of early detection and treatment of renal damage to slow CKD progression and thereby prevent adverse clinical outcomes, which necessitates early monitoring of urinary protein in clinical practice to identify early signs of kidney impairment.
Detailed data from the FIGARO-DKD trial confirm the cardiovascular benefits of finerenone demonstrated in the FIDELIO-DKD trial. The FIGARO-DKD trial focused on patients with chronic kidney disease (CKD) and type 2 diabetes across varying disease severities (stages 1 to 4). Over a median follow-up of 3–4 years, compared with placebo plus guideline-directed medical therapy at maximum tolerated doses, finerenone significantly reduced the risk of the composite endpoint (first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) by 13% (hazard ratio [HR] 0.87 [95% CI: 0.76–0.98]; p = 0.0264). In the FIGARO-DKD trial, finerenone was well tolerated, with a safety profile consistent with previously reported data. The FIGARO-DKD trial substantially strengthens the evidence for the cardiovascular benefits of finerenone across different disease stages. Building upon the FIDELIO-DKD data, it further demonstrates that finerenone improves both the composite renal endpoint and the key secondary composite cardiovascular endpoint in the majority of patients with stage 3–4 CKD and severely elevated urinary albumin.
The FIDELITY study is a pre-specified pooled analysis encompassing 13,000 patients from the FIGARO-DKD and FIDELIO-DKD trials, demonstrating that finerenone provides renal and cardiovascular benefits in patients with chronic kidney disease and type 2 diabetes. In the FIDELITY analysis, compared with placebo, finerenone reduced the risk of the composite cardiovascular endpoint (including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) by 14% (HR: 0.86 [95% CI: 0.78–0.95]; p = 0.0018). Compared with placebo, finerenone reduced the risk of the composite kidney endpoint (onset of kidney failure, a sustained decrease in eGFR of ≥57% from baseline for ≥4 weeks, or death from kidney causes) by 23% (HR: 0.77 [95% CI: 0.67–0.88]; p = 0.0002). Kidney endpoint events occurred in 360 patients (5.5%) in the finerenone group, compared with 465 patients (7.1%) in the placebo group.