title: [Efficacy and safety of long-term application of spironolactone in patients with moderate and severe chronic heart failure receiving optimal therapy].
abstract: Aim of the investigation was the study of influence of spironolactone (25 - 75 mg/day) on clinico-functional status, parameters of left ventricular (LV) remodeling, as well as safety of its long term application in patients with chronic heart failure (CHF) receiving optimal therapy. Forty nine patients were included in the study - 44 men (89,8%) and 5 women (10,2%) in the age from 28 to 75 years with II-IV NYHA functional class (FC) CHF, LV ejection fraction (EF) 35%, plasma levels of creatinine 150 mmol/L and potassium 5 mmol/L. Main causes of development of CHF were dilated cardiomyopathy, ischemic heart disease (large focal postinfarction cardiosclerosis) and decompensated hypertensive heart [25/20/4 (51%/40,8%/8,2%), respectively]. As a result of randomization procedure 2 groups of observation were formed: group 1 - 19 patients receiving spironolactone in a 24 hour dose 25 - 75 mg, group 2 - control group - 30 patients without therapy with spironolactone. Inhibitors of angiotensin converting enzyme (ACE) took 100%, b-adrenoblockers - 63,2% of patients. Control examination was conducted before randomization, in 6 and 12 months of follow up. During period of observation no changes of FC were noted in control group. In the group of treatment with spironolactone after 6 months in 6 patients FC lowered ( =0,028). By the end of follow up the given effect lost its significance, but 5 (38,5%) patients by termination of the study had FC II of CHF, what was accompanied with moderate increase of distance walked during 6-minute walk test from 354 to 378 m. In patients in the group of spironolactone treatment already after 6 months of treatment there occurred decrease of LV volumes, what by the end of period of observation for LV end diastolic volume (EDV) amounted - 76 ( - 118; - 7), and for LV end systolic volume (ESV) - 53 ml ( - 96; - 7) ml ( =0,008) at absolute increment of LVEF by 3 (0; 12)% ( =0,05). In control group in 12 months decrease of LVEDV was less pronounced and LV ESV did not change. Finally after 12 months of observation the groups became to differ by change of LVEF ( =0,035) and LVESV ( =0,02). Changes of LV volumes were followed by lowering of median concentration of atrial natriuretic peptide (ANP) in plasma by - 51,9 ( - 87; - 43,9) mg/ml. At the same time in control group gradual rise of concentration of the given peptide was observed from initial 107,3 to 168,5 mg/ml at the moment of study termination. Changes of BP level, creatinine concentration in patients in the study were not fixed in any of treatment groups. Development of moderate hyperkaliemia amounted 21.0%, gynecomastia or pain in the region of mammary glands were fixed in 26,3% of patients in 12 months of treatment. Addition of spironolactone in a dose of 75 mg/day to optimal therapy, including ACE inhibitor and b-adrenoblocker is accompanied with improvement of clinical state and FC of patients with moderate and severe CHF. Long term therapy with spironolactone blocks processes of desadaptive LV remodeling and improves LV contractile function, what is reflected in lowering of ANP concentration in plasma of patients with CHF. Application of spironolactone in combination with ACE inhibitor and b-adrenoblocker bisoprolol does not lead to lowering of BP level and worsening of renal function, but is accompanied with development of hyperkaliemia in patients with CHF. Gynecomastia appears to be main reason limiting long term use of spironolactone in patients with CHF in a dose of 75 mg/day.
authors.affiliation: Cardiology Research Complex, ul. Tretiya Cherepkovskaya 15a, 121552 Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Skvortsov
authors.forename: V Yu
authors.initials: VY
authors.lastname: Mareev
authors.forename: S M
authors.initials: SM
authors.lastname: Chelmakina
authors.forename: N A
authors.initials: NA
authors.lastname: Baklanova
authors.forename: Iu N
authors.initials: IuN
authors.lastname: Belenkov
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D012720:Severity of Illness Index; D013148:Spironolactone / Q000008:administration & dosage*; D013318:Stroke Volume / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone