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

Abstract

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).