VALSARTAN, A NEW ANGIOTENSIN-II ANTAGONIST FOR THE TREATMENT OF ESSENTIAL-HYPERTENSION - EFFICACY, TOLERABILITY AND SAFETY COMPARED TO AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, LISINOPRIL

Objective: To compare the efficacy, safety and tolerability of valsart an to an angiotensin-converting enzyme (ACE) inhibitor, lisinopril, an d placebo in patients with mild-to-moderate essential hypertension. De sign: A total of 734 men and women were randomised in this multicentre , double-blind, optional titration, parallel group trial. Volunteers r eceived valsartan 80 mg (n = 364), lisinopril 10 mg (n = 187) or place bo (n = 183) daily for 4 weeks, with subsequent titration of dose depe nding on response to treatment (valsartan 80 mg titrated to valsartan 160 mg once daily or valsartan 80 mg twice daily, lisinopril 10 mg tit rated to lisonopril 20 mg once daily). Patients were assessed at 4, 8 and 12 weeks. Main outcome measures: The primary Variable was change f rom baseline in mean sitting diastolic blood pressure (SDBP). Other ef ficacy variables included sitting systolic blood pressure (SSBP) and p ercentage of 'successful' responders (SDBP <90 mmHg or greater than or equal to 10 mm Hg reduction from baseline). Results: All active treat ment groups were shown to demonstrate significant reductions in SDBP c ompared to placebo at endpoint of therapy (least mean square reduction from baseline: valsartan 80/160 mg: -5.25 mm Hg (CI -7.17, -3.34, P< 0.001); valsartan 80/80 mg twice daily: -5.63 mm Hg (Cl -7.51, -3.75, P < 0.001); lisinopril 10/20 mg: -6.93 mmHg, (CI -8.81, -5.05, P< 0.00 1). There were no statistically significant differences between the ac tive treatment groups at endpoint of therapy. In patients requiring ti tration to a higher dose (placebo n = 142, valsartan 80/80 twice daily n = 124, valsartan 80/160 n = 114, lisinopril 10/20 n = 120), there w ere no significant treatment differences between valsartan 160 mg give n as a single daily dose or as 80 mg twice daily (P = 0.658). Both val sartan and lisinopril produced similarly high percentages of 'successf ul' responders at endpoint of therapy. A somewhat higher frequency of drug related cough was observed in lisinopril treated patients (8%) co mpared to valsartan (1.1%) or placebo (0.5%). Conclusions: Valsartan 8 0 mg daily, with titration to 160 mg daily as required, provides simil ar antihypertensive efficacy to lisinopril 10 mg daily with titration to 20 mg daily. Valsartan provides a new antihypertensive agent with c omparable efficacy to lisinopril and appears to be associated with a r educed incidence of cough.