LONG-TERM EVALUATION OF COMBINED ANTIHYPERTENSIVE THERAPY WITH LISINOPRIL AND A THIAZIDE DIURETIC IN PATIENTS WITH ESSENTIAL-HYPERTENSION

For the treatment of hypertension, the combination of an angiotensin-c onverting enzyme (ACE) inhibitor and a thiazide diuretic is supported by multiple lines of evidence, because these drugs have synergistic ac tion and are expected to cancel out each other's adverse side effects. However, the longterm outcome of this combination antihypertensive th erapy is not entirely clear. In the present multicenter open trial, we investigated the long-term efficacy and safety of combined antihypert ensive therapy with an ACE inhibitor, lisinopril, and a thiazide diure tic, trichlormethiazide. A total of 466 patients with essential hypert ension were treated with lisinopril alone (monotherapy group, n = 360) or with a combination of lisinopril with trichlormethiazide (combinat ion therapy group, n = 106) for 1 year. The average blood pressure was effectively lowered to below 150/90 mmHg in both the monotherapy and the combination therapy groups throughout the study period. The averag e maintenance dose of lisinopril was lower when combined with thiazide than when given alone (9.8 vs. 11.5 mg/day, p < 0.001). Dry cough was the major side effect of lisinopril; no severe adverse effects were o bserved. The incidence of cough was not significantly different betwee n the monotherapy group (13.1%) and the combination therapy group (11. 3%). The increase in serum potassium observed in the monotherapy group was reversed by the concurrent use of the thiazide diuretic in the co mbination therapy group. Fasting blood glucose was significantly reduc ed in the monotherapy group; the reduction observed in the combination therapy group was not significant. Thus, the present results provide useful information as to the effectiveness and safety of combined anti hypertensive therapy with lisinopril and a thiazide in comparison with monotherapy with lisinopril.