EFFECTS OF ENALAPRIL ON CLINICAL, NONINVASIVE HEMODYNAMIC AND NEUROENDOCRINE INDEXES IN ELDERLY PATIENTS (AGED GREATER-THAN-75 YEARS) WITH HEART-FAILURE

Background The prevalence of heart failure increases markedly with age . Although angiotensin converting enzyme (ACE) inhibitors have been sh own to be very effective treatment for heart failure in younger patien ts, there have been no substantial controlled studies in elderly patie nts. Age and differences in the aetiology of heart failure may alter n euroendocrine activation in health and heart failure. The neuroendocri ne response to ACE inhibition has not previously been described in ver y elderly patients with heart failure. Objective To determine the effe cts of a 6-week course of enalapril at a target dose of 16 mg once dai ly on the plasma concentrations of active renin, angiotensin II, aldos terone, atrial natriuretic peptide and noradrenaline in a group of eld erly patients with heart failure and left ventricular systolic dysfunc tion. Patients and study design Twelve patients greater than 75 years old (mean age 82 years) with heart failure, treated with diuretics and with echocardiographic evidence of left ventricular systolic dysfunct ion, were enrolled. Patients were assessed clinically by a corridor wa lking test, echocardiography and radionuclide ventriculography after a 4-week placebo run-in period to ensure stability and after 6 weeks' t reatment with enalapril. Venous blood samples were extracted for the m easurement of haematocrit, urea and electrolytes, and neuroendocrine i ndices. Results Ten patients completed the study. Seven patients recei ved in mg daily enalapril but three could tolerate only 5 mg daily bec ause of hypotension or dizziness. Despite a rise in radionuclide eject ion fraction and a marked fall in atrial natriuretic factor, no signif icant improvement in symptoms or corridor walking distance was noted. Reductions in angiotensin II and aldosterone were similar in magnitude to those observed with younger patients, but the rise in renin, due t o release from the negative feedback effect of angiotensin II, appeare d blunted. Plasma noradrenaline concentrations were elevated markedly at baseline, compared with Values reported in younger patients with he art failure, but did not fall during treatment with enalapril. Conclus ions The response of the renin-angiotensin-aldosterone system to enala pril in elderly patients with heart failure seems similar to that repo rted in younger subjects. Plasma atrial natriuretic peptide falls in r esponse to ACE inhibition. Insofar as both the clinical and the progno stic benefits of ACE inhibition have been related to reductions in neu roendocrine activity, this implies that similar benefits might be obta ined by elderly patients with heart failure. However, plasma concentra tions of noradrenaline, which also may be of prognostic value in heart failure, were elevated markedly and did not fall after 6 weeks of tre atment with enalapril. The small study size may have prevented the det ection of clinical benefit, but this was not the primary objective of the study.