M. Simunic et al., RAMIPRIL DECREASES CHLORTHALIDONE-INDUCED LOSS OF MAGNESIUM AND POTASSIUM IN HYPERTENSIVE PATIENTS, Journal of clinical pharmacology, 35(12), 1995, pp. 1150-1155
A double-blind clinical trial was conducted to compare the efficacy of
and electrolyte changes caused by ramipril-chlorrhalidone combination
treatment (5 mg +/- 25 mg) and chlorthalidone monotherapy (25 mg dail
y) in patients with hypertension. After a l-week placebo period, 32 pa
tients (mean age, 51 +/- 9 years) with essential hypertension (average
blood pressure of 181.4/104.5 +/- 13.0/6.9 mmHg) were randomly assign
ed to receive combination therapy (group A, n = 17) or monotherapy (gr
oup B, n = 15). After 12 weeks of active treatment, systolic and diast
olic blood pressure decreased by 16.1% and 13%, respectively, for pati
ents taking combined therapy, and by 12.7% and 9.8%, respectively, for
patients taking monotherapy. The difference was significant for betwe
en-group comparisons. There were no changes in serum sodium concentrat
ion, but a significant similar increase in 24-hour urinary sodium excr
etion was seen in both groups. Serum calcium levels increased slightly
and 24-hour urinary calcium excretion decreased significantly in both
groups, probably due to chlorthalidone administration. Serum potassiu
m levels increased slightly in group A (from 4.16 +/- 0.39 mmol/L to 4
.30 +/- 0.42 mmol/L) and decreased slightly in group B (from 4.18 +/-
0.32 mmol/L to 3.99 +/- 0.49 mmol/L). Urinary potassium excretion did
not change significantly in group A, but increased by similar to 15% i
n group B. There runs a decrease in 24-hour urinary magnesium excretio
n (from 4.01 +/- 1.24 mmol/24 hours to 3.50 +/- 0.93 mmol/24 hours) in
group A and an increase (from 3.49 +/- 0.98 mmol/24 hours to 4.35 +/-
1.12 mmol/24 hours) in group B. At the end of the trial these changes
were significant in between-group comparisons. Consistent with the pr
eviously shown amelioration by ramipril of thiazide-induced metabolic
side-effects, ramipril appears to improve magnesium balance during cot
reatment with chlorthalidone.