Comparative studies: enalapril versus hydrochlorothiazide as first-step therapy for the treatment of primary...

Thirty-nine patients were entered into a 12-week, randomized, double-blind, parallel protocol to assess the safety and efficacy of enalapril (MK-421, 10 to 20 mg bid), hydrochlorothiazide (HCTZ, 25 to 50 mg bid), or combined drug therapy (MK-421 + HCTZ) for the treatment of primary hypertension. Specifically monitored were the effects of each drug program on BP and pulse, serum chemistries, body fluid composition and weight, renal function, and the renin-angiotensin-aldosterone axis. Results indicate that MK-421, HCTZ, and combined therapy were equally effective in lowering BP; none of the therapies significantly altered glomerular filtration rate or effective renal plasma flow. Patients on MK-421 experienced no change in volume, an increase in plasma potassium, no change in fractional sodium or potassium excretion, and a decreased urine osmolality associated with an enhanced free-water clearance. Plasma renin activity was increased, plasma angiotensin II was decreased, and plasma aldosterone was unchanged. In contrast, patients on HCTZ developed volume contraction, hypokalemia associated with an increase in fractional sodium and potassium excretion, and an increased urine osmolality associated with a decreased free-water clearance. Plasma renin activity was increased, however, plasma angiotensin II and plasma aldosterone were unchanged. Patients on combined therapy with MK-421 + HCTZ demonstrated qualitatively similar changes in serum chemistries, body fluid volumes, and renal function compared with patients receiving HCTZ alone, whereas changes in the renin-angiotensin-aldosterone system in these patients were qualitatively similar, but more marked, compared with those occurring in patients receiving MK-421 alone. We conclude that MK-421 is an effective first-step antihypertensive agent that does not produce adverse metabolic, volume, or renal effects.