Optimizing GDMT in Heart Failure Could Slash Global Mortality Rates

Gregg C. Fonarow, MD

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Optimal utilization of guideline-directed medical therapy (GDMT) in heart failure could significantly benefit global mortality rates, according to a new report published in JAMA Cardiology.¹

This report showed an improved implementation of GDMT could prevent an estimated 1.19 million deaths per year on a global scale, with more than 1 million deaths prevented in regions including the Eastern Mediterranean and Africa, Southeast Asia, and the Western Pacific.

“This study highlights significant population-level mortality benefits with optimization of GDMT quadruple therapy on a global level and provides insights on regional differences that may better inform worldwide efforts for heart failure management,” wrote the investigative team, led by Gregg C. Fonarow, MD, division of cardiology, UCLA.

Global underutilization of GDMT has been reported, despite its strong benefits for efficacy and mortality rates.² Previous investigations into the mortality benefits of the individual components of GDMT have mainly focused on the US, making the projected benefits of global GDMT optimation for heart failure with reduced ejection fraction (HFrEF) unknown.³

For this analysis, Fonarow and colleagues sought to evaluate the projected benefit of optimal GDMT use in a worldwide population with HFrEF.¹ The number of patients eligible for GDMT was determined based on estimates of heart failure prevalence from the Global Burden of Disease study. Those with contraindications to GDMT were estimated from US registries and applied globally.

Treatment rates and the number needed to treat for all-cause mortality at 12 months were calculated from previously published methods. Approximately 29 million people are estimated to have HFrEF worldwide, of which 8,235,063 and 12,223,700 were potentially eligible for, but not receiving β-blockers or angiotensin receptor–neprilysin inhibitors (ACEI/ARB), respectively.

Further estimates showed 12,223,700 and 21,229,170 individuals were eligible for, but not receiving mineralocorticoid receptor antagonists (MRA) or sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Upon analysis, the optimal implementation of quadruple GDMT therapy on a global scale could save an estimated 1,188,277 lives over 12 months, particularly in the prevention of cardiovascular mortality. Benefits were most apparent in Southeast Asia and the Western Pacific, for a combined 720,054 averted deaths.

Fonarow and colleagues found angiotensin receptor-neprilysin inhibitors (ARNIs) and SGLT2 inhibitors comprised the largest proportion of averted deaths, at 29.5% and 28.4%, respectively. On the other hand, the optimal use of β-blockers saved approximately 24.8% of lives, while MRAs led to 17.4% of total lives saved globally.

The investigative team noted the rates of lives saved with optimal GDMT utilization were partially driven by the fact that a notable proportion of the global HFrEF population live in these regions, but experience low current treatment rates. These data suggest the heterogeneity of GDMT use globally and the potential magnitude of improvement with better GDMT utilization.

“Although future studies are needed to better understand the heterogeneity that exists within each region and potential interventions targeted to different settings, these findings demonstrate the urgent need for improved implementation of GDMT therapies worldwide,” they wrote.

References

1. _{Tang AB, Ziaeian B, Butler J, Yancy CW, Fonarow GC. Global Impact of Optimal Implementation of Guideline-Directed Medical Therapy in Heart Failure. JAMA Cardiol. Published online October 02, 2024. doi:10.1001/jamacardio.2024.3023}
2. _{Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2023 Apr 18;81(15):1551. doi: 10.1016/j.jacc.2023.03.002]. J Am Coll Cardiol. 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012}
3. _{Fonarow GC, Yancy CW, Hernandez AF, Peterson ED, Spertus JA, Heidenreich PA. Potential impact of optimal implementation of evidence-based heart failure therapies on mortality. Am Heart J. 2011;161(6):1024-30.e3. doi:10.1016/j.ahj.2011.01.027}