Muthiah Vaduganathan, MD, MPH, is a cardiologist specializing in cardiorenal metabolism at Brigham and Women's Hospital in Boston, MA. Vaduganathan is a member of Practical Cardiology's advisory board and co-host of Don't Miss a Beat, a podcast presented by Inside Cardiology.

Muthiah Vaduganathan, MD, MPH

Finding a Role for GLP-1 RAs, Incretin Therapies in Heart Failure, with Muthiah Vaduganathan, MD, MPH

GLP-1 receptor agonists and combination incretin therapies have taken the medical community by storm in recent years with trial after trial proving benefits on outcomes across a multitude of diseases, including weight management, secondary prevention of cardiovascular disease, and, now, obesity-related heart failure with preserved ejection fraction (HFpEF) based on data from the SUMMIT trial.

A multicenter, randomized, double-blind, parallel, placebo-controlled phase 3 trial, SUMMIT assessed the safety and efficacy of tirzepatide among a cohort of 731 adult patient adults with HFpEF and obesity, with or without type 2 diabetes, enrolled at sites in 10 countries across 4 continents. The trial leveraged a pair of primary outcomes of interest—a composite of time-to-first occurrence of urgent heart failure visit, heart failure hospitalization, oral diuretic intensification and cardiovascular death to study completion and the change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) from baseline to week 52.

Results of the trial suggested a composite endpoint event occurred among 9.9% of the tirzepatide group and 15.3% of the placebo group (HR, 0.62; 95% CI, 0.41 to 0.95; 

 = .026). Analysis of KCCQ-CSS at 52 weeks suggested use of tirzepatide was associated with a mean change of 19.5 (SD, 1.2) from baseline to week 52 compared to a change of 12.7 (SD, 1.3) among the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; 

Although not examining hospitalization outcomes, SUMMIT is the second trial to demonstrate meaningful changes in quality of life among patients with obesity-related HFpEF, with the STEP-HFpEF program finding benefit on KCCQ with use of semaglutide.

American Heart Association (AHA) Annual Scientific Sessions 2024

, Muthiah Vaduganathan, MD, MPH, codirector of the Center for Cardiometabolic Implementation Science of Brigham and Women’s Hospital, took part in a debate session where he argued in favor of a role for GLP-1 receptor agonists in heart failure care. As part of our on-site coverage of AHA 24, we sat down with Vaduganathan to learn more about how he envisions GLP-1 receptor agonists and incretin therapies fitting into heart failure care in light of recent data.

 include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others.

Tirzepatide for Patients with Heart Failure with Preserved Ejection Fraction and Obesity: the SUMMIT Trial

. Paper presented at: American Heart Association Scientific Sessions 2024; November 15 - 18; Chicago, Il. Accessed November 16, 2024.

Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. 

. 2023;389(12):1069-1084. doi:10.1056/NEJMoa2306963

Videos

GLP-1 receptor agonists and combination incretin therapies have shown significant benefits in managing obesity-related heart failure with preserved ejection fraction (HFpEF), as evidenced by the SUMMIT trial. This phase 3 trial demonstrated that tirzepatide significantly reduced composite endpoint events and improved quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), compared to placebo. These findings align with previous results from the STEP-HFpEF program using semaglutide. The role of GLP-1 receptor agonists in heart failure care is gaining support among experts.

Muthiah Vaduganathan, MD, MPH, discusses the need for cardiology to embrace a role for GLP-1 receptor agonists and incretin therapies, with a focus on obesity-related HFpEF.

Don't Miss a Beat: Putting Evidence-Based Cardiometabolic Therapies into Practice, with Taher Modarressi, MD

Acquiring Expertise in Cardiometabolic Health - 02:29

Advice for Aspiring Cardiometabolic Health Specialists - 04:09

Practical Aspects of Running a Cardiometabolic Practice - 07:30

Navigating Insurance and Cost Barriers - 08:43

Implementing Effective Systems for Therapy Implementation - 09:22

Practical Tips for Implementing Cardiometabolic Therapies - 20:21

In this episode of Don't Miss a Beat, hosts Muthiah Vaduganathan, MD, MPH, a cardiologist and codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, and Steve Greene, MD, an advanced heart failure specialist at Duke University School of Medicine, sit down with Taher Modarressi, MD, a cardiometabolic health specialist, to discuss the practical challenges of integrating cardiometabolic therapies into clinical practice.
Modarressi, who launched and owns a standalone practice in the Princeton, NJ area, shares his perspective on his career, what led to establishing the clinic, and the steps he takes to ensure the successful implementation of new therapies, such as GLP-1 receptor agonists and SGLT2 inhibitors, for complex, chronic conditions, including diabetes, obesity, and cardiovascular disease. During the conversation, Modarressi highlights the critical role of insurance coverage, patient assistance programs, and prior authorizations in ensuring patients can access these life-changing therapies.
Modarressi also provides practical tips and nuggets of wisdom on how clinicians can work to streamline the process of helping patients obtain guideline-recommended therapies by working with them to understand insurance formularies, using copay cards, and leveraging tools, like CoverMyMeds, for prior authorizations.

All episodes of Don’t Miss a Beat are available in an audio-only format on 

 include Amgen, Novo Nordisk, Abbott Laboratories, and Boston Scientific. Relevant disclosures for 

 include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for 

 include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others.

Podcasts

Taher Modarressi, MD, sits down with hosts to share tips and practical nuggets for cardiometabolic health specialists to optimize prescription and adherence to newer therapies. 

Don't Miss a Beat: Finerenone's Role in Heart Failure from ESC Congress 2024

01:18 - FINEARTS Study Design and Patient Population

03:04 - Inclusion of Hospitalized Patients

05:56 - Challenges in Achieving Statistical Significance

07:39 - Health Status Improvement and Additional Analyses

10:01 - Combination Therapy and Future Trials

12:20 - Hyperkalemia and Steroidal vs. Non-Steroidal MRAs

Already renowned as the world’s largest annual cardiology meeting, the 2024 iteration of the 

European Society of Cardiology (ESC) Congress

 may also be remembered as the dawn of a new era in heart failure, with the landmark FINEARTS-HF trial proving finerenone (Kerendia) offered significant benefits in a population of 

 with a left ventricular ejection fraction (LVEF) greater than 40%.

The trial itself found itself as the subject of a special Hot Line session at the meeting, which featured a total of 3 presentations: FINEARTS-HF, FINE-HEART, and a meta-analysis of MRA use in patients with heart failure.

In this ESC Congress 2024 edition of Don’t Miss a Beat, Stephen Greene, MD, an advanced heart failure specialist at Duke University School of Medicine, discusses the prospect of finerenone in treatment algorithms for heart failure with Muthiah Vaduganathan, MD, MPH, codirector of the Center for Cardiometabolic Implementation Science of Brigham and Women’s Hospital, who served as an investigator on the FINEARTS-HF trial and presenter of FINE-HEART.

In the trial, use of finerenone was associated with a statistically significant 16% relative reduction in rate of primary outcome events compared with placebo therapy (rate ratio [RR], 0.84; 95% confidence interval [CI], 0.74 to 0.95; 

 = 0.007). Specifically, 1083 primary outcome events occurred among 624 patients in the finerenone group and 1283 primary outcome events occurred among 719 patients in the placebo group.

Data from ESC Congress 2024 offered further insight into the trial, with analysis of individual components of the primary endpoint revealing use of finerenone was associated with an 18% relative reduction in incidence of heart failure hospitalization (RR, 0.82; 95% CI, 0.71 to 0.94; 

 = .006) and nonsignificant 7% relative risk reduction for death from cardiovascular causes (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Additional data from ESC Congress 2024 demonstrated there was no differences between the finerenone and placebo groups for all-cause mortality (HR, 0.93; 95% CI 0.83–1.06) or the composite kidney outcome (HR, 1.33; 95% CI, 0.94 to 1.89).

Analysis of individual components of the primary endpoint revealing use of finerenone was associated with an 18% relative reduction in incidence of heart failure hospitalization (RR, 0.82; 95% CI, 0.71 to 0.94; 

 = .006) and nonsignificant 7% relative risk reduction for death from cardiovascular causes (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Additional data from ESC Congress 2024 demonstrated there was no statistically significant differences observed between the finerenone and placebo groups for all-cause mortality (HR, 0.93; 95% CI, 0.83 to 1.06) or the composite kidney outcome (HR, 1.33; 95% CI, 0.94 to 1.89).

Following the presentation of the FINEARTS-HF trial, Vaduganathan presented data from the FINE-HEART study, which was a prespecified analysis FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF aimed at describing the safety and efficacy of finerenone on cardiovascular, kidney, and mortality outcomes using participant-level data.

From the 3 trials, investigators formed a study cohort of 18,991 participants. This cohort had a mean age of 67 (SD, 10) years, 35% were women, and the median follow-up was 2.9 years.

Results of the analysis indicated use of finerenone contributed to a nonsignificant reduction in the relative risk of cardiovascular death compared to placebo therapy (4.44% vs 5.0%; HR, 0.89; 95% CI, 0.78 to 1.01; 

= .076). Further analysis revealed finerenone use was associated with statistically significant reactions in the risk of all-cause mortality (HR, 0.91; 95% CI, 0.84 to 0.99; 

 = .027), risk of heart failure hospitalization (HR, 0.83; 95% CI, 0.75 to 0.92; 

<.001) and the composite kidney outcome (HR, 0.80; 95% CI, 0.72 to 0.90; 

Safety analyses revealed finerenone use was associated with a reduced risk of adverse events than placebo (34.6% vs 36.6%), but serious adverse events leading to drug discontinuation were greater with finerenone (5.4% vs. 4.6%). Additionally, results suggested laboratory-defined hyperkalemia was greater with finerenone whereas laboratory-defined hypokalemia was lower. 

include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for

include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others.

SD Solomon, JJV McMurray, M Vaduganathan, et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. Presented at: European Society of Cardiology Congress 2024. August 30 - September 2, 2024. London, UK.

M Vaduganthan, G Filippatos, BL Claggett, et al. Finerenone in Heart Failure and Chronic Kidney Disease with Type 2 Diabetes: the FINE-HEART pooled analysis of cardiovascular, kidney, and mortality outcomes. Presented at: European Society of Cardiology Congress 2024. August 30 - September 2, 2024. London, UK.

In this episode, Muthiah Vadugnathan, MD, MPH, and Stephen Greene, MD, discuss finerenone and MRA data from ESC Congress 2024.

Don't Miss a Beat: Finerenone's Role in Heart Failure from ESC Congress Data

Don't Miss a Beat: Semaglutide and the Future of Kidney Disease, with Brendon Neuen, MBBS, PhD

Semaglutide and the Future of Kidney Disease, with Brendon Neuen, MBBS, PhD

The rise of semaglutide (Ozempic, Wegovy) is a phenomenon unlike any other witnessed in modern healthcare. Outside of vaccinations, there are few examples of agents commanding the same level of attention as the GLP-1 receptor agonist, which has captured the eye of both the medical community and general public alike with its promise of 

Semaglutide, and the GLP-1 receptor agonist class as a whole, has distanced itself from previous notions suggesting its role was solely for improving glucose control. Among the public, this was driven by results of trials purporting historic benefits in weight loss, which led to approvals for weight management.

Next, semaglutide captivated the general public and medical community alike with revelations of its cardiovascular benefits among patients with overweight or obesity and a history of cardiovascular disease without diabetes. This trial, which examined the 2.4 mg dose of semaglutide, was used as the basis of a first-of-its-kind indication from the US Food and Drug Administration in March 2024.

At the 61st European Renal Association Conference, the latest landmark trial offered evidence that could lead to an additional label expansion from the FDA: 

. The trial, which was stopped early due to efficacy, examined use of the 1.0 mg dose of semaglutide for kidney outcomes in patients with type 2 diabetes at risk for chronic kidney disease—the first GLP-1 receptor agonist trial to do so.

The trial concluded use of semaglutide 1.0 mg was associated with a 24% relative risk reduction for a composite endpoint of dialysis, transplantation, an eGFR decline to less than 15 ml/min/1.73m2, a reduction of 50% or greater in eGFR from baseline, or death from kidney-related or cardiovascular causes. Secondary endpoint analyses from the trial also garnered considerable attention, including a statistically significant 20% reduction in all-cause mortality.

The overlap between the fields extends not only to therapies, but also evolutions in conceptual approach to management with many in nephrology now advocating for a pillared approach to chronic kidney disease management, much like the field of heart failure has adopted in recent years.

With interest in the evolving landscape of chronic kidney disease, the cardiorenal protective effects of GLP-1 receptor agonist therapies, and other updates from the world of nephrology, Don’t Miss a Beat hosts Muthiah Vaduganathan, MD, MPH, co-director of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, and Steve Greene, MD, advanced heart failure specialist at the Duke Clinical Research Institute, sit down with Brendon Neuen, MBBS, PhD, nephrologist and director of the Kidney Trials Unit at Royal North Shore Hospital and senior research fellow at The George Institute for Global Health.

 include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for 

 include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Relevant disclosures for 

 include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others.

Campbell P. Semaglutide (Wegovy) approved for chronic weight management in patients with obesity or overweight. HCP Live. April 17, 2023. Accessed May 29, 2024. https://www.hcplive.com/view/semaglutide-approved-for-chronic-weight-management-in-patients-with-obesity-or-overweight.

Campbell P. Semaglutide (Wegovy) receives FDA label expansion to include cardiovascular risk reduction. HCP Live. March 8, 2024. Accessed May 29, 2024. https://www.hcplive.com/view/semaglutide-wegovy-receives-fda-label-expansion-to-include-cardiovascular-risk-reduction.

Campbell P. Flow trial fortifies SEMAGLUTIDE’s role in chronic kidney disease and type 2 diabetes. HCP Live. May 24, 2024. Accessed May 29, 2024. https://www.hcplive.com/view/flow-trial-fortifies-semaglutide-s-role-in-chronic-kidney-disease-and-type-2-diabetes.

Brendon Neuen, MBBS, PhD, joins the podcast to discuss the latest updates in nephrology, including the landmark FLOW trial.

Muthiah Vaduganathan, MD, MPH

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