Research shows that current guidelines for medical therapies at recommended doses are under-utilised in patients with heart failure with reduced ejection fraction (HFrEF). With improved uptake and uptitration of guideline-directed medical therapies, better patient outcomes can be achieved. 

When given a prescription with an increase in the amount of medication to consume, one may naturally be concerned and feel uneasy about the state of their health condition. Conversely, recent research shows that it is important to have medical therapies at the recommended guidelines for heart failure, whereby an uptitration of drugs dosage can result in better outcome for patients.

In a first-ever, multinational real-world data examination of prescription patterns and doses attained for guideline-directed medical therapies in Asian patients suffering from heart failure with HFrEF (refer to visual below), a team of researchers found that the 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) registry. These findings were first published in The Lancet Global Health journal on September 2018.

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 (where 1066 participants are from Singapore), and studied the prescription patterns and doses attained of guideline-directed medical therapies in Asian HFrEF patients, and the associations with patient outcomes. The research team made the following two observations:

1) Recommended Doses Are Under-utilised

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) [these medications help relax blood vessels] as firstline 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; Singapore fared slightly better with the two medications prescribed at 71%. The
under-utilisation of such guideline-directed medical therapies at recommended doses was associated with poorer patient outcomes.

2) 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 adhered to by 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. 

Key Takeaways

The current analysis represents essential registry data to help guide 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. There is also
limited data on heart failure in multi-regional Asians, who characteristically have smaller body sizes.

The Principal Investigator of ASIAN-HF, Professor Carolyn Lam (Senior Consultant from Department of Cardiology, and Director of Clinical Trials at the NHCS) 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 outcomes.”

“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 NHCS.

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 on the importance of guideline-directed medical therapy at targeted doses.

(Click on the above image to expand.)

This article is from Murmurs Issue 32 (Sep – Dec 2018). Click here to read the full issue.