1150 #{149} J ClIn Pharmacol 1995;35:1150-1155 Ramipril Decreases Chiorthalidone- Induced Loss of Magnesium and Potassium in Hypertensive Patients Miroslav Simuni, MD, Zvonko Rum boldt, MD, PhD, FCP, Dragan Ljutid MD, PhD, and Sanda Sarde1ic, MD A double-blind clinical trial was conducted to compare the efficacy of and electrolyte changes caused by ramipril-chlorthalidone combination treatment (5 mg + 25 mg) and chlOrthalidone monotherapy (25 mg daily) in patients with hypertension. After a 4-week placebo period, 32 patients (mean age, 51 ± 9 years) with essential hypertension (average blood pressure of 181.4/104.5 ± 13.0/6.9 mmHg) were randomly assigned to receive com- bination therapy (group A, n = 17) or nlonotherapy (group B, n = 15). After 12 weeks of active treatment, systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively, for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for patients taking monotherapy. The difference was significant for between-group com- parisons. There were no changes in serum sodium concentration, but a significant similar increase in 24-hour urinary sodium excretion 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 potassium levels increased slightly in group A (from 4.16 ± 0.39 mmol/L to 4.30 ± 0.42 mmol/L) and de- creased 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 ‘-15% in group B. There was a decrease in 24-hour urinary magnesium excretion (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 previously shown amelioration by ramipril of thiazide-induced metabolic side-effects, ramipril ap- pears to improve magnesium balance during cotreatment with chlorthalidone. C linical studies carried out over the last decade have led to a greater understanding of the role of electrolytes in the pathogenesis of essential hyper- tension. Moreover, the importance of electrolyte ab- normalities induced by antihypertensive treatment also is better understood. The focus of these studies has been mainly sodium and potassium, calcium to a lesser extent, and magnesium only recently.1 It is already well established that high sodium in- take is associated with high blood pressure, and that administration of diuretic agents leads to natriuresis, which is the principal mode of action of these From the Department of Medicine, Clinical Hospital Split, Croatia. Ad- dress for reprints: Zvonko Rumboldt, MD, PhD, FCP, Department of Medicine, Clinical Hospital Split, Spini#{243}eva 1, 58 000 Split, Croatia. agents.2 Potassium intake correlates negatively with the magnitude of blood pressure, and hypokalemia presents one of the unfavorable effects of diuretic therapy. In contrast, large studies have not shown good correlation between calcium intake and blood pressure.3 The debate about the importance of magnesium depletion during antihypertensive treatment still ex- ists. Magnesium is an essential cofactor in more than 300 enzymatic systems. Under normal circum- stances the kidney is the prime regulator of magne- sium balance; approximately 60% of filtered Mg is reabsorbed in the thick ascending portion of Henle’s loop.4 Consequently, loop diuretics induce marked urinary loss of magnesium, whereas thiazides pro- voke a lesser but still significant loss of magnesium. Thiazide diuretics are now considered an appropri-