Medical therapy for heart failure: the evidence exists, but is it being followed?
Authors: Hisham Dokainish
Journal: The Lancet Global Health (2018)

Although heart failure is a major cause of morbidity and mortality worldwide,1Ambrosy AP Fonarow GC Butler J et al.The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries.J Am Coll Cardiol. 2014; 63: 1123-1133Crossref PubMed Scopus (1303) Google Scholar effective medical therapy to reduce morbidity and mortality exists and data (albeit from western countries only) have shown improvements in outcomes in the past decade.2Krumholz HM Normand SL Wang Y Trends in hospitalizations and outcomes for acute cardiovascular disease and stroke, 1999–2011.Circulation. 2014; 130: 966-975Crossref PubMed Scopus (162) Google Scholar It is still unknown how closely practitioners follow guideline-directed medical therapy for heart failure, particularly in non-western areas of the world. In their Article3Teng THK Tromp J Tay WT et al.PPrescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: a cohort study.Lancet Glob Health. 2018; 6: e1008-e1015Summary Full Text Full Text PDF PubMed Scopus (82) Google Scholar published in The Lancet Global Health, Tiew-Hwa K Teng and colleagues present novel and important data on the utilisation and dosing of guideline-directed medical therapy in patients with heart failure and reduced ejection fraction (HFrEF) from the ASIAN-HF registry, an observational cohort study of 5276 patients with HFrEF from 46 centres in 11 regions in Asia. The authors found substantial regional variations among Asian countries in the prescription and dosing of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists (MRAs). They also observed frequent use of only one of these medications—as opposed to combination therapy, as recommended by guidelines4Ponikowski P Voors AA Anker SD et al.2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.Eur Heart J. 2016; 37: 2129-2200Crossref PubMed Scopus (8726) Google Scholar—and widespread under-achievement of guideline-recommended dosing. Patients from wealthier Asian countries were significantly more likely to be prescribed combination therapy compared with patients from poorer countries, where monotherapy was more common. There were also major regional variations in the type of medication for heart failure that was most commonly used. For example, uptake of β blockers varied from 95% in Singapore to 61% in Indonesia; use of MRAs varied from 78% in China to 40% in Hong Kong; and use of ACE inhibitors or ARBs varied from 87% in Indonesia to 60% in China. Although the reasons for these regional variations are unclear, local culture or preference and cost might be key factors. The most important finding of this study is how low the achievement of guideline-recommended dosing was in Asian countries (17% for ACE inhibitors or ARBs, 13% for β blockers and 29% for MRAs), and that the lower the dose of guideline-directed medical therapy achieved, the higher the rates of death and heart failure-related admission to hospital. Notably, achievement of guideline-recommended dosing was similar to that of a European study5Ouwerkerk W Voors AA Anker SD et al.Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.Eur Heart J. 2017; 38: 1883-1890Crossref PubMed Scopus (224) Google Scholar (22% for ACE inhibitors or ARBs and 12% for β blockers), which also showed that guideline-recommended dosing was associated with improved patient outcomes. These data show that in Asia, Europe, and probably in most (if not all) areas of the world, achievement of guideline-recommended dosing can be improved and could result in important gains in survival and reductions in heart failure-related admission to hospital. However, there are some important factors to consider when interpreting these findings. First, medication prescription differs from adherence (whether the patient actually takes the prescribed medication); the latter requires time-consuming, and often impractical, measures—such as pill counting. Poor adherence to medication in patients with heart failure is associated with worse outcomes, including poor survival.6Wu JR Moser DK De Jong MJ et al.Defining an evidence-based cutpoint for medication adherence in heart failure.Am Heart J. 2009; 157: 285-291Summary Full Text Full Text PDF PubMed Scopus (105) Google Scholar Reasons for non-adherence include financial factors, side-effects, and unavailability of medications, particularly in poorer regions of the world.7Khatib R McKee M Shannon H et al.Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data.Lancet. 2016; 387: 61-69Summary Full Text Full Text PDF PubMed Scopus (227) Google Scholar Second, despite adjustment for baseline characteristics and region within Asia, there might still be factors (not accounted for in the multivariable model) that affect why guideline-recommended dosing of medications for heart failure is so low and related to worse outcomes. For example, patients who are frail might be less likely to achieve guideline-recommended doses, possibly owing to polypharmacy, comorbidity, multi-organ dysfunction, and reduced blood pressure, and frailty itself is an important predictor of poor outcomes.8Martín-Sánchez FJ Rodríguez-Adrada E Vidan MT et al.Impact of frailty and disability on 30-day mortality in older patients with acute heart failure.Am J Cardiol. 2017; 120: 1151-1157Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar Third, region within Asia had a powerful effect on outcomes. Patients in southeast Asia had almost double the adjusted risk of death at 1 year, compared with patients from northeast and south Asia. Regional variation in heart failure-related outcomes in Asia was also seen in the INTER-CHF study,9Dokainish H Teo K Zhu J et al.Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study.Lancet Glob Health. 2017; 5: e665-e672Summary Full Text Full Text PDF PubMed Scopus (178) Google Scholar wherein patients with heart failure from India had more than 3 times, and patients from southeast Asia had more than 2·7 times, the adjusted hazard of death within 1 year, compared with patients from China. In ASIAN-HF, although there was no interaction between region and outcomes for ACE inhibitors or ARBs and MRAs, region did modify the association between β blockers and combined outcome. Therefore, region could also affect the effectiveness of some medical therapy in reducing adverse events in patients with heart failure; however, the potential reasons for this are unclear and require further study. Important questions remain: what are the barriers to attainment of guideline-recommended doses in patients with heart failure? Why is monotherapy for heart failure still prevalent despite guidelines? Why is there substantial variability in which medications for heart failure are most commonly used among different countries? What are workable programmes that can be implemented regionally to improve use of guideline-directed medical therapy and attainment of guideline-recommended dosing among patients with heart failure? This study provides important data on HF medication use and its impact on outcomes from a pan-Asian population with heart failure that has, until now, not been well characterised. Major areas of opportunity in the management of heart failure in Asia are reducing monotherapy (in favour of combination therapy) and improving guideline-recommended dosing of medications. These are areas that nationwide education and quality improvement programmes can target, which will help to improve care and patient outcomes for a disease that has been referred to as a global pandemic.10Mehra MR Butler J Heart failure: a global pandemic and not just a disease of the west.Heart Fail Clin. 2015; 11: 13-14Summary Full Text Full Text PDF Scopus (6) Google Scholar I declare no competing interests. Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: a cohort studyGuideline-directed medical therapies at recommended doses are underutilised in patients with HFrEF. Improved uptake and uptitration of guideline-directed medical therapies are needed for better patient outcomes. Full-Text PDF Open Access