Are there benefits of low doses of ACE inhibitors, MRAs, diuretics and statins in the treatment of heart failure?




chronic heart failure, ACE inhibitors, MRAs, diuretics, statins, treatment


Treatment of chronic heart failure (CHF) is very controversial. The issue of optimal doses of beta-blockers, ACE inhibitors, aldosterone receptor antagonists, statins in patients with CHF has not been conclusively addressed. Achieving the maximum tolerated doses of drugs, though related to reduced mortality, but is accompanied by an increase in adverse drug reactions.

The aim. To present and discuss our own clinical and scientific data concerning the role of beta-blockers and inhibitors of the renin-angiotensin aldosterone system, diuretics, statins in the treatment of CHF patients and optimization of dosage schemes.

Material and methods. The study included 88 patients with CHF of ischemic origin, with sinus rhythm, stage II AB, NYHA FC II–IV, 58 – with reduced LV EF (HFrEF) and 30 – with preserved LV EF (HFpEF). The mean age of patients was 69.18 ± 9.97 years, men 52 % (n = 46). The median follow-up of the CHF patients was 396 days, the maximum number of follow-up days was 1302. During the observation period, 14 endpoints were registered, which accounted for 15.91 % of events: 7 deaths (8.0 %), 2 strokes (2.3 %), 2 cases of acute coronary syndrome (2.3 %), 3 progressive heart failure cases (3.4 %).

Kaplan–Mayer curves were drawn to assess survival rate, and the significance of difference between groups was calculated by the criteria of Gehan–Wilcoxon, Cox–Mantel and log-rank test. Risk factors were determined, and prognostic uni- and multi-variant Cox proportional hazards regression models were used. The cut-off values of quantitative risk factors were obtained by ROC analysis.

Results. The increase in the relative risk of adverse cardiovascular events in the CHF patients regardless of LV EF was associated with a daily carvedilol dose of more than 25 mg (HR = 1.05; 95 % CI 1.009–1.093; P = 0.0171); eplerenone – more than 12.5 mg (HR = 1.073; 95 % CI 1.005–1.144; P = 0.034), torasemide – more than 5 mg (HR = 1.13; 95 % CI 1.021–1.255; P = 0.019); rosuvastatin – more than 10 mg (HR = 1.107; 95 % CI 1.007–1.203; P = 0.035), and the trend in using atorvastatin at a dose of less than 10 mg (HR = 1.05; 95 % CI 0.951–1.165; P = 0.327). The use of ramipril in a daily dose of less than 2.5 mg was accompanied by a trend towards the 22 % reduced relative risk of adverse cardiovascular events (HR = 0.78; 95 % CI 0.384–1.580; P = 0.491).

Conclusions. Positive treatment outcomes in the CHF patients, regardless of the phenotype, were associated with low daily doses of ramipril (<2.5 mg), eplerenone/spironolactone (<12.5 mg), torasemide (<5.0 mg), rosuvastatin (<10.0 mg), but with high doses of atorvastatin (>10.0 mg).

Author Biography

V. А. Lysenko, Zaporizhzhia State Medical University, Ukraine

MD, PhD student of the Department of Propaedeutics of Internal Medicine, Radiation Diagnostics and Therapy


Abebe, T. B., Gebreyohannes, E. A., Tefera, Y. G., Bhagavathula, A. S., Erku, D. A., Belachew, S. A., Gebresillassie, B. M., & Abegaz, T. M. (2018). The prognosis of heart failure patients: Does sodium level play a significant role?. PloS one, 13(11), e0207242.

Kosmas, C. E., Silverio, D., Sourlas, A., Montan, P. D., & Guzman, E. (2018). Role of spironolactone in the treatment of heart failure with preserved ejection fraction. Annals of translational medicine, 6(23), 461.

Ferreira, J. P., Mentz, R. J., Pizard, A., Pitt, B., & Zannad, F. (2017). Tailoring mineralocorticoid receptor antagonist therapy in heart failure patients: are we moving towards a personalized approach?. European journal of heart failure, 19(8), 974-986.

Voronkov, L. H., Amosova, K. M., Dziak, H. V., Zharinov, O. Y., Kovalenko, V. M., Korkushko, O. V., Nesukai, O. H., Parkhomenko, O. M., Rudyk, Yu. S., & Sychov, O. S. (2017). Rekomendatsii Asotsiatsii kardiolohiv Ukrainy z diahnostyky ta likuvannia khronichnoi sertsevoi nedostatnosti (2017) [Recommendation of Association of Cardiologists of Ukraine for the treatment of chronic heart failure in adults (2017)]. Kyiv. [in Ukranian].

Khan, M. S., Fonarow, G. C., Ahmed, A., Greene, S. J., Vaduganathan, M., Khan, H., Marti, C., Gheorghiade, M., & Butler, J. (2017). Dose of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Outcomes in Heart Failure: A Meta-Analysis. Circulation. Heart failure, 10(8), e003956.

Ferreira, J. P., Rossello, X., Eschalier, R., McMurray, J., Pocock, S., Girerd, N., Rossignol, P., Pitt, B., & Zannad, F. (2019). MRAs in Elderly HF Patients: Individual Patient-Data Meta-Analysis of RALES, EMPHASIS-HF, and TOPCAT. JACC. Heart failure, 7(12), 1012-1021.

Fudim, M., Kelly, J. P., Brophy, T. J., DeVore, A. D., Hammill, B. G., Peterson, E. D., Pitt, B., Yancy, C., Fonarow, G. C., & Hernandez, A. F. (2020). Trends in Treatment for Patients Hospitalized with Heart Failure with Preserved Ejection Fraction Before and After Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT). The American journal of cardiology, 125(11), 1655-1660.

Murphy, S. P., Ibrahim, N. E., & Januzzi, J. L., Jr (2020). Heart Failure With Reduced Ejection Fraction: A Review. JAMA, 324(5), 488-504.

Edelmann, F., Wachter, R., Schmidt, A. G., Kraigher-Krainer, E., Colantonio, C., Kamke, W., Duvinage, A., Stahrenberg, R., Durstewitz, K., Löffler, M., Düngen, H. D., Tschöpe, C., Herrmann-Lingen, C., Halle, M., Hasenfuss, G., Gelbrich, G., Pieske, B., & Aldo-DHF Investigators (2013). Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA, 309(8), 781-791.

Chen, Y., Wang, H., Lu, Y., Huang, X., Liao, Y., & Bin, J. (2015). Effects of mineralocorticoid receptor antagonists in patients with preserved ejection fraction: a meta-analysis of randomized clinical trials. BMC medicine, 13, 10.

Tsuda, K., Kataoka, Y., Ogata, S., Nishimura, K., Nishikawa, R., Doi, T., Nakashima, T., Hosoda, H., Honda, S., Kawakami, S., Fujino, M., Nakao, K., Yoneda, S., Nishihira, K., Otsuka, F., Tahara, Y., Asaumi, Y., Hoshiga, M., Noguchi, T., & Yasuda, S. (2020). Diminished response to statins predicts the occurrence of heart failure after acute myocardial infarction. Cardiovascular diagnosis and therapy, 10(4), 705-716.

Takano, H., Mizuma, H., Kuwabara, Y., Sato, Y., Shindo, S., Kotooka, N., Fujimatsu, D., Kobayashi, Y., Inoue, T., Node, K., Komuro, I., & PEARL Study Investigators (2013). Effects of pitavastatin in Japanese patients with chronic heart failure: the Pitavastatin Heart Failure Study (PEARL Study). Circulation journal, 77(4), 917-925.

Erbs, S., Beck, E. B., Linke, A., Adams, V., Gielen, S., Kränkel, N., Möbius-Winkler, S., Höllriegel, R., Thiele, H., Hambrecht, R., & Schuler, G. (2011). High-dose rosuvastatin in chronic heart failure promotes vasculogenesis, corrects endothelial function, and improves cardiac remodeling--results from a randomized, double-blind, and placebo-controlled study. International journal of cardiology, 146(1), 56-63.

Ashton, E., Windebank, E., Skiba, M., Reid, C., Schneider, H., Rosenfeldt, F., Tonkin, A., & Krum, H. (2011). Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study. International journal of cardiology, 146(3), 404-407.

Qu, H., Meng, Y. Y., Chai, H., Liang, F., Zhang, J. Y., Gao, Z. Y., & Shi, D. Z. (2018). The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials. European journal of medical research, 23(1), 57.




How to Cite

Lysenko VА. Are there benefits of low doses of ACE inhibitors, MRAs, diuretics and statins in the treatment of heart failure?. CIPM [Internet]. 2021Jun.1 [cited 2023Dec.3];14(2):226-31. Available from:



Original research