Optimization of Medical Treatment in Heart Failure with Reduced Ejection Fraction and Clinical Outcomes in the New Era


  • Orawan Anupraiwan, M.D. Cardiovascular and Intervention Department, Central Chest Institute of Thailand
  • Yuppadee Innoi, Pharm. D. Department of pharmacy, Central Chest Institute of Thailand
  • Kriengkrai Hengrussamee, M.D. Bangkok Heart Hospital


Heart failure with reduced ejection fraction, Optimization of medical treatment, Target dose, Clinical outcomes


Background: Patients with heart failure are at risk of rehospitalization and high mortality. Current heart failure guidelines recommend the evidence-based pharmacological management for heart failure with reduced ejection fraction (HFrEF) to improve clinical outcomes. The challenge is how to construct optimal treatment for better results and minimized adverse events in clinical practice.Objective: We aimed to determine the association between patients with HFrEF who were prescribed target or optimal dose of medications and clinical outcomes.Methods: This was an analytic study in patients with HFrEF from January 2008 to December 2019. Primary outcome was the composite of cardiovascular death or heart failure hospitalization. The secondary outcome was all-cause death. Univariate and multivariate analysis were used to estimate the independent effects of predictor variables and survival.Results: There were 345 patients were enrolled with mean age 58.34 ± 12.97 years. The majority of patients were male, NYHA functional class I-II and non-ischemic cardiomyopathy. Few patients were achieved target dose of ACEI/ARB (16.81%), beta-blockers (47.09%), spironolactone (6.34%) and ARNI (13.95%). At follow up, patients who received < 50% target dose of beta-blockers and ACEI/ARB were associated with more primary outcome (log rank p < 0.01), whereas those who received spironolactone cannot demonstrate the difference in outcome (log rank p = 0.09). In multivariate analysis, NYHA functional class III-IV (p = 0.003) and atrial fibrillation (p = 0.007) were an independent predictor of worse clinical outcomes. While, patients with improve LVEF (p < 0.001) and received ≥ 50% target dose of ACEI/ARB (p = 0.017) were an independent predictor of favorable outcomes.Conclusion: This study demonstrated significant gaps between clinical practice and guideline-directed medical therapy in current era of HFrEF therapies. Patients who received neurohormonal blockade medications ≥ 50% dosage of target dose were associated with improve LVEF and better outcomes.


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Author Biography

Orawan Anupraiwan, M.D., Cardiovascular and Intervention Department, Central Chest Institute of Thailand

Central Chest Institute of Thailand


Krittayaphong R, Laothavorn P, Hengrussamee K, Sanguanwong S, Kunjara-Na-Ayudhya R, Rattanasumawong K, et al. Ten-year survival and factors associated with increased mortality in patients admitted for acute decompensated heart failure in Thailand. Singapore Med J 2020; 61: 320-6.

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, 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; 37:2129-200.

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/ AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136: e137-e161.

Maddox TM, Januzzi JL Jr, Allen LA, Breathett K, Butler J, Davis LL, et al. 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure with Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021; 77: 772-810.

B ua kh am s ri A, Ch i ra ka r nj an ak o rn S, Sa n gu an w on g S , Porapakkham P, Kanjanavanich R. Heart Failure Council of Thailand (HFCT) 2019 heart failure guideline: pharmacologic treatment of chronic heart failure-part I. J Med Assoc Thai 2019;102:240-4.

Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, et al. The EuroHeart Failure Survey programmea survey on the quality of care among patients with heart failure in Europe: Part 2: treatment. Eur Heart J 2003;24:464-74.

Fonarow GC, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, et al. Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF). Circulation 2010;122:585-96.

Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, et al. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry. J Am Coll Cardiol 2018; 72:351-66.

McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381:1995–2008.

Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020; 383:1414–24.

Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation 1999; 100:2312–8.

Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation 1996; 94:2807–16.

Kalra PR, Morley C, Barnes S, Menown I, Kassianos G, Padmanabhan S, et al. Discontinuation of beta-blockers in cardiovascular disease: UK primary care cohort study. Int J Cardiol 2013; 167:2695–99.

Gheorghiade M, Albert NM, Curtis AB, Thomas Heywood J, McBride ML, Inge PJ, et al. Medication dosing in outpatients with heart failure after implementation of a practice-based performance improvement intervention: findings from IMPROVE HF. Congest Heart Fail 2012;18:9-17.

Ouwerkerk W, Voors AA, Anker SD, Cleland JG, Dickstein K, Filippatos G, 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: 1883-90.

Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet 2009; 374:1840-8.

Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Eng J Med 1999;341:709-17.

Tavazzi L, Senni M, Metra M, Gorini M, Cacciatore G, Cacciatore G, et al. IN-HF (Italian Network on Heart Failure) Outcome Investigators. Multicenter prospective observational study on acute and chronic heart failure: one-year follow-up results of IN-HF (Italian Network on Heart Failure) outcome registry. Circ Heart Fail 2013;6:473-81.

Maggioni AP, Dahlström U, Filippatos G, Chioncel O, Crespo Leiro M, Drozdz J, et al. Heart Failure Association of the European Society of Cardiology (HFA). EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 2013;15:808-17.

Basuray A, French B, Ky B, Vorovich E, Olt C, Sweitzer NK, et al. Heart failure with recovered ejection fraction: clinical description, biomarkers, and outcomes. Circulation 2014;129:2380-7.

Florea VG, Rector TS, Anand IS, Cohn JN. Heart Failure with Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results from the Valsartan Heart Failure Trial. Circ Heart Fail 2016;9: e003123.

Park CS, Park JJ, Mebazaa A, Oh IY, Park HA, Cho HJ, et al. Characteristics, Outcomes, and Treatment of Heart Failure with Improved Ejection Fraction. J Am Heart Assoc 2019;8: e011077.



How to Cite

Anupraiwan O, Innoi Y, Hengrussamee K. Optimization of Medical Treatment in Heart Failure with Reduced Ejection Fraction and Clinical Outcomes in the New Era. j dept med ser [Internet]. 2022 Jan. 21 [cited 2022 Dec. 7];46(4):81-90. Available from: https://he02.tci-thaijo.org/index.php/JDMS/article/view/250576



Original Article