O'Neil, Catherine Jane; (1992) Maintenance therapy of heart failure in the elderly patient: Studies on the efficacy and toxicity of two angiotensin converting enzyme inhibitors. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Methodology has been developed to evaluate the efficacy and toxicity of two angiotensin converting enzyme (ACE) inhibitors when either was used as an adjuvant to digoxin and diuretic therapy in the treatment of frail elderly heart failure patients. In an open study of enalapril only 11/17 patients mean (SD) age 83 (5) y tolerated its cautious introduction (1 patient died despite uneventful introduction of enalapril). Compliance (pill counts) was excellent in the 9/10 patients continued in the trial. When the functional ability was assessed in a symptom limited walking test (SWT), there was nearly a three-fold increase in distance walked and a two-fold increase in walking speed within one week of starting enalapril. Although performance was maintained at this level for at least 3 months, the patients actually reported a worsening of some of their symptoms. Furthermore, beyond 3 months 8/10 patients experienced adverse effects which necessitated the withdrawal of enalapril. The benefits of captopril an ACE inhibitor with a shorter plasma half-life were examined in a randomised, placebo-balanced, crossover trial. Twenty-six patients, mean (SD) age 82 (6) were recruited. Adverse effects led to withdrawal of captopril in 6 patients in the pre-trial period. Compliance (monitored "pill box") was excellent in the remaining 20 patients who were entered into the trial. This consisted of 3 treatment periods, a twice daily dosage of captopril established during a titration period, once daily captopril (half the above), and the placebo, each treatment period lasting for 3 weeks. Functional ability was assessed by gait analysis (GA) and SWT. Walking tended to be best on the once daily captopril treatment and worst on placebo. When the effects of serum ACE activity and blood pressure were taken into account in a linear model a statistically significant (P=0.04) treatment effect on SWT distance was revealed. No such effect was observed on oxygen consumption or ventilation volume in a tailored exercise protocol. Plasma atrial natriuretic factor (ANF) reflects the degree of cardiac compromise. An analytical method was developed to measure ANF in human plasma. Pre-exercise levels of ANF were significantly lower on the captopril treatments than on placebo, but still remained four-fold higher in patients than in 11 healthy age-matched subjects. Furthermore, unlike the control group, there was no apparent increase in ANF response to exercise in the patients. On completing the crossover study patients entered an open study on twice daily captopril. A slight deterioration in gait was observed in these patients after 3 months. Captopril appeared to be relatively well tolerated during the trial: only 3/20 patients (1 during the crossover, 2 during the open study), experienced adverse effects which led to the withdrawal of captopril.

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