Media Release

​Study showed improved outcomes for heart failure patients if guideline-directed medical therapies are followed

Singapore, 15 October 2018 – In a first-ever prospective, multinational real-world data examination1 of prescription patterns and doses attained of guideline-directed medical therapies in Asian patients suffering from heart failure with reduced ejection fraction (HFrEF2), a team of researchers found that guideline-directed medical therapies at recommended doses are under-utilised in these patients enrolled from across 11 Asian regions in the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry3. These findings were recently published in The Lancet Global Health journal which selects high quality research papers for publication.

The research team, of which eight investigators are from Singapore, analysed prospective data of 5,276 HFrEF patients enrolled in the ASIAN-HF registry since 2012, and studied the prescription patterns and doses attained of guideline-directed medical therapies in Asian HFrEF patients, and the associations with patient outcomes. The team made two observations:

Guideline-directed medical therapies at recommended doses are under-utilised in HFrEF patients
The current evidence-based guidelines for best practice recommend that HFrEF treatment consists of trial-directed doses for angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists (ARBs) and beta-blockers (ß blockers) as first-line therapy, and mineralocorticoid receptor antagonists (MRAs) as second-line therapy.

Instead of combined therapy, it was observed that monotherapy – that is, only ACE inhibitors, ARB or ß blockers – has been prescribed. Despite regional variation across the countries in prescription patterns, the guideline-recommended combination of ACE inhibitors or ARB and ß blockers was prescribed in only 55% (or 2,914 patients) of the overall ASIAN-HF cohort of 5,276 HFrEF patients. The under-utilisation of such guideline-directed medical therapies at recommended doses was associated with poorer patient outcomes.

Widespread under-dosing
The failure to achieve the recommended doses of guideline-directed medical therapies was widespread. The recommended doses of ACE inhibitors or ARB were reached in only 17% of the patients, compared with 13% for ß blockers and 29% for MRAs.

When analysing the relationship between prescribed doses and one-year hospitalisation for heart failure or all-cause mortality rates in HFrEF patients, it was observed that even small doses of ACE inhibitors or ARB and ß blockers were associated with lower hospitalisation or mortality rates within a year, compared with no dose or non-usage in the overall ASIAN-HF cohort. However, full recommended doses were associated with the best outcomes.

The current analysis represents the best available evidence for clinicians treating HFrEF in Asia as there is no other contemporary data from across the region on prescription patterns and doses attained of guideline-directed medical therapies in patients with HFrEF.

The Principal Investigator of ASIAN-HF, Professor Carolyn Lam (Senior Consultant, Department of Cardiology at the National Heart Centre Singapore and Professor, Duke-NUS Cardiovascular Academic Clinical Program) said, “The good news is that we are providing the appropriate types of therapies for the majority of our patients in Asia, and that even low doses of these medications are better than none. However, these data also highlight treatment gaps where we may improve upon. This is all the more important in Southeast Asian patients with heart failure, who are on average at least a decade younger than their US or European counterparts, and yet suffer more severe clinical symptoms and worse outcomes4,5,6,7,8.”

“Our study’s findings support as well as provide valuable insights into the importance of guideline recommendations to start evidence-based therapies in those who are not receiving any therapy, and to increase the doses of ACE inhibitors or ARBs and ß blockers to the maximum level of toleration, to achieve maximum benefits among Asian patients with HFrEF,” added Dr Katherine Teng, first author of the research paper and Senior Research Fellow at the National Heart Centre Singapore.

To address the knowledge and treatment gaps, the research findings suggest the need for interventions such as enhancing the efforts and education among physicians to improve the uptake of evidence-based practices and uptitration of guideline-directed medical therapies in the management of heart failure patients; and raising awareness among patients of the importance of guideline-directed medical therapy at targeted doses.


  1. “Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: a cohort study”, Tiew-Hwa K Teng, Jasper Tromp, Wan Ting Tay, Inder Anand, Wouter Ouwerkerk, Vijay Chopra, Gurpreet S Wander, Jonathan JL Yap, Michael R MacDonald, Chang Fen Xu, Yvonne MF Chia, Wataru Shimizu, ASIAN-HF investigators, A Mark Richards, Adriaan Voors, Carolyn SP Lam, The Lancet Global Health 6 (2018) pp. 1008-1018

  2. Heart failure with reduced ejection fraction (HFrEF) occurs when the left side of one’s heart does not pump blood out to the body as well as normal. The ejection fraction (or EF, the amount of blood that is pumped from the heart’s left ventricle with each beat) is 40% or less. Heart failure with preserved ejection fraction (HFpEF) is a form of congestive heart failure wherein the ejection fraction is greater than 50%. [Source:]

  3. “Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry”, Lam CS, Anand I, Zhang S, Shimizu W, Narasimhan C, Park SW, Yu CM, Ngarmukos T, Omar R, Reyes EB, Siswanto B, Ling LH, Richards AM. Eur J Heart Fail. 2013;15(8):928-36.

    The Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry gathers and analyses baseline clinical characteristics and outcomes of HFrEF (EF<40%) and HFpEF (EF≥50%) patients from 11 Asian regions, grouped as Northeast Asia (Hong Kong, Taiwan, China, Japan and Korea); South Asia (India); and Southeast Asia (Malaysia, Thailand, Singapore, Indonesia, Philippines). The ASIAN-HF study is supported by grants from the National Research Foundation Singapore under its Translational and Clinical Research (TCR) Flagship Programme administered by the Singapore Ministry of Health’s National Medical Research Council; the Asian Network for Translational Research and Cardiovascular Trials (ATTRaCT) programme funded by the Agency for Science, Technology and Research; Boston Scientific Investigator Sponsored Research Program; and Bayer.

  4. “Heart failure in Southeast Asia: facts and numbers”, Carolyn S.P. Lam, National Heart Centre Singapore, ESC Heart Failure (2015); 2: 46-49

    Southeast Asia is home to a growing population of more than 600 million people, with a majority over 65 years old. Factors such as ageing population and rapid epidemiological transition have led to high rates of premature death from non-communicable diseases (namely, cardiovascular disease which include heart failure) in Asia. The rise in the risk factors of heart failure will inevitably increase the epidemic of heart failure. A World Health Organisation 2014 global status report shows that the prevalence of Stage A heart failure risk factors, particularly hypertension, tobacco smoking, physical inactivity and raised blood glucose (diabetes), is especially high in Southeast Asia. This prevalence of symptomatic heart failure appears to be higher in Southeast Asia, as compared with the rest of the world, despite a low prevalence of obesity (which is closely linked to diabetes among Western patients).

  5. “Patient characteristics from a regional multicenter database of acute decompensated heart failure in Asia Pacific (ADHERE International-Asia Pacific)”, Atherton JJ, Hayward CS, Wan Ahmad WA, Kwok B, Jorge J, Hernandez AF, Liang L, Kociol RD, Krum H. ADHERE International-Asia Pacific Scientific Advisory Committee. J Card Fail 2012;18:82–88

  6. “Heart failure care in low- and middle-income countries: a systematic review and meta-analysis”, Callender T, Woodward M, Roth G, Farzadfar F, Lemarie JC, Gicquel S, Atherton J, Rahimzadeh S, Ghaziani M, Shaikh M, Bennett D, Patel A, Lam CS, Sliwa K, Barretto A, Siswanto BB, Diaz A, Herpin D, Krum H, Eliasz T, Forbes A, Kiszely A, Khosla R, Petrinic T, Praveen D, Shrivastava R, Xin D, MacMahon S, McMurray J, Rahimi K. PLoS Med 2014;11:e1001699

  7. “Trends and ethnic differences in hospital admissions and mortality for congestive heart failure in the elderly in Singapore, 1991 to 1998”, Ng TP, Niti M. , Heart 2003;89:865–870

  8. “Impact of race on morbidity and mortality in patients with congestive heart failure: a study of the multiracial population in Singapore“, Lee R, Chan SP, Chan YH, Wong J, Lau D, Ng K. Int J Cardiol 2009;134:422–425.

About the National Heart Centre Singapore
The National Heart Centre Singapore (NHCS, 新加坡国家心脏中心) is a 185-bed national and regional referral centre for cardiovascular diseases. A one-stop facility with the largest heart specialists group in Singapore, NHCS treats complex cases and sees the highest volume of heart patients locally.

Each year, the Centre handles over 120,000 outpatient consultations, 6,000 interventional and surgical procedures and 9,000 inpatients. Its outcomes for heart attack treatment, balloon angioplasty with stenting and coronary bypass surgery have been shown to be equivalent to international standards.

A pioneer and leader in cardiovascular care in Singapore and the region, NHCS is the first specialty heart centre in Singapore.
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