A COMPARISON OF THE CHRONIC EFFECTS OF ORAL XAMOTEROL AND ENALAPRIL ON BLOOD-PRESSURE AND RENAL-FUNCTION IN MILD TO MODERATE HEART-FAILURE

1 We compared the effects, after 3 weeks oral therapy, of xamoterol 200 mg twice daily and enalapril 2.5, 5 or 10 mg twice daily on home and clinic blood pressure, glomerular filtration rate (GFR) and renal plasma flow, stroke and minute distances, linear resistance and on plasma renin activity in 19 patients with mild to moderate heart failure in a single-blind randomised crossover study. 2 Enalapril reduced mean home blood pressure by 17/7 mm Hg compared with xamoterol (P < 0.0001) and by 19/7 mm Hg compared with placebo. Compared with placebo xamoterol had no effect. Enalapril reduced predose blood pressure, compared with xamoterol, on average by 15/5 mm Hg (P = 0.02 systolic, 0.09 diastolic) and by 20/7 mm Hg compared with placebo. At 4 h post-dose the mean differences were: xamoterol-enalapril 13/10 mm Hg (P = 0.01 systolic, 0.0007 diastolic) and placebo-enalapril 23/9 mm Hg. 3 Stroke and minute distances were marginally less 4 h following xamoterol than following enalapril: mean (s.e. mean) values were 9.4 (0.7) vs 10.4 (0.8) cm (P = 0.23) and 699 (51.7) vs 767 (62.1) cm (P = 0.04) respectively. Linear resistance was reduced by enalapril, from the placebo value of 13.2 (1.2) to 11.0 (0.9) mm Hg m-1 and marginally increased by xamoterol, to 14.2 (1.2) mm Hg m-1, the difference between active treatments being statistically significant (P = 0.03). 4 Renal plasma flow, GFR and filtration fraction were not influenced by enalapril or xamoterol therapy. There were no significant correlations between glomerular filtration rate and either blood pressure or stroke distance. Neither xamoterol nor enalapril had any significant effect on these relationships. The changes in GFR seen in individual patients were not determined by age, baseline left ventricular ejection fraction, baseline renal function or diastolic blood pressure. There were weak, but statistically significant, negative correlations between baseline systolic blood pressure and enalapril- (but not xamoterol-) related change in GFR and between baseline 24 h urinary sodium excretion and xamoterol- (but not enalapril-) related change in GFR. 5 After 3 weeks enalapril increased pre-dose plasma renin activity (PRA) from 5.8 (placebo) to 13.4 ng AI ml-1 min-1 and 4 h post-dose PRA from 6.5 to 25.6 ng AI ml-1 min-1 (P < 0.01 in both cases). Xamoterol had no substantial effect on PRA. 6 One patient died during post-enalapril placebo washout. Symptoms probably or possibly related to drug therapy were more frequent with enalapril than with xamoterol. 7 Xamoterol 200 mg twice daily does not share the daytime hypotensive effect of enalapril. The effect of enalapril on blood pressure is mediated through a fall in vascular resistance, with no reduction in cardiac output, and is not reflected in altered renal haemodynamics. Xamoterol does not appear to compromise renal function in these patients.