Heart Failure in Asian Populations

More than 60% of global cardiovascular disease originates from the Asia-Pacific; yet, there has been little improvement in recruiting Asian clinical trial participants (Video). As such, more representation is required among clinical trial participants to affect change in the wide prevalence of heart failure and poor outcomes of patients suffering from it.^1,2

Data from the CDC Wonder Database in the United States facilitated a national assessment of cardiovascular risk factors and disease mortality among Asian Indian, Chinese, and Filipino American subgroups. Findings emphasized that it would be detrimental to consider Asian Americans a monolith and that accounting for individual Asian ethnicities and cardiovascular risk factors is crucial to efficacious care.³ These groups have distinct cardiovascular health challenges, and targeted public health efforts to reduce cardiovascular mortality are necessary. Tailoring screening, diagnosis, and prevention strategies to unique risk profiles could help decrease cardiovascular risk. Current risk equations for determining the probability of cardiovascular disease fail to account for the elevated risk in this group, especially the higher family history–based risk.⁴

In Asia, the prevalence of heart failure is high. China, Indonesia, and Malaysia are the 3 countries with high age-standardized prevalence of heart failure within Asia. Although absolute numbers of heart failure prevalence increased in Asia over time, the age-standardized numbers only increased in Southeast Asia and South Asia. Phenotypes of heart failure vary depending on country and region. For example, ischemic cardiomyopathy is the most common cause of heart failure in South and Southeast Asia, and nonischemic disease as an etiology is more prevalent in East Asia. Ischemic heart disease and hypertensive heart disease are the foremost heart failure causes globally and in Asia. One-year mortality of Asian patients with heart failure remains elevated, especially in Southeast and South Asia, and the primary cause of death in heart failure is cardiovascular death.⁵

Despite the high prevalence of heart failure in Asia, guideline-concordant prescribing rates are low. A 2018 study showed suboptimal prescription rates for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (77%), beta blockers (79%), and mineralocorticoid receptor antagonists (58%), with considerable variability by country in Asia. Notably, fewer than a quarter of patients were receiving treatment at recommended doses.⁶

Clinical trials demonstrate both the efficacy of medications to treat heart failure with reduced ejection fraction in these populations and the gap in using them. A meta-analysis showed that sodium-glucose cotransporter 2 inhibitors effectively reduced the risk of the composite outcome in both Asian and White patient groups. If anything, the effectiveness of sodium-glucose cotransporter 2 inhibitors seemed to be more prominent among Asian patients than in White patients.⁷

In the PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] With ACEI [Angiotensin-Converting–Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial of sacubitril/valsartan vs enalapril, there was a lower rate of hospitalization for heart failure and higher mortality in South Asian individuals than in other groups. Further, the overall mortality due to cardiovascular causes or any cause was greater in Asian patients vs the overall PARADIGM-HF group. There was a similar treatment benefit in Asian patients as in the overall PARADIGM-HF population and among the different Asian regions.⁸ In DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin vs placebo reduced the risk of worsening heart failure events and cardiovascular death similarly in Asian patients as in other populations.⁹ The EMPEROR-Reduced (Empagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) trial showed the magnitude of the effect of empagliflozin on the primary composite outcome (cardiovascular death or hospitalization for worsening heart failure) and total hospitalizations for heart failure was prominent in Asia. In addition, the magnitude of the effect on those same outcomes was at least as good in Black patients and Asian patients as in White patients.¹⁰

Thus, the randomized data to date support similar efficacy of evidence-based therapies in Asian patients as in non-Asian patients. We need to do a better job of ensuring these patients benefit from all the advances in heart failure therapies.

Funding Support and Author Disclosures

Dr Bhatt discloses the following relationships: Advisory Board: Angiowave, Antlia Bioscience, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, E-Star Biotech, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, NirvaMed, Novo Nordisk, Repair Biotechnologies, Stasys, and Tourmaline Bio; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); Consultant: Alnylam, Altimmune, Broadview Ventures, Corcept Therapeutics, Corsera, GlaxoSmithKline, Hims, SERB, SFJ, Summa Therapeutics, and Worldwide Clinical Trials; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research, Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (American Heart Association lecture), Duke Clinical Research Institute, Engage Health Media, HMP Global (Editor in Chief, Journal of Invasive Cardiology), Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Philips (Becker's Webinar on AI), Population Health Research Institute, WebMD (CME steering committees), and Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor) and Progress in Cardiovascular Diseases (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Alnylam, Amarin, Amgen, AstraZeneca, Atricure, Bayer, Boehringer Ingelheim, Boston Scientific, CellProthera, Cereno Scientific, Chiesi, Cleerly, CSL Behring, Faraday Pharmaceuticals, Fractyl, Idorsia, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, MiRUS, Moderna, Novartis, Novo Nordisk, Pfizer, PhaseBio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, and 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); and Site Co-Investigator: Cleerly.