Use of losartan in the treatment of hypertensive patients with a history of cough induced by angiotensin-converting enzyme inhibitors.

The objective of this study was to determine the incidence of dry cough in hypertensive patients with a history of angiotensin-converting enzyme (ACE) inhibitor-induced cough after treatment with losartan (an angiotensin II-receptor antagonist), lisinopril (an ACE inhibitor), or placebo. One hundred patients from 16 outpatient treatment centers in the United States were included in this double-masked, randomized, parallel-group, active- and placebo-controlled study, with stratification according to sex. After a challenge phase with lisinopril and a placebo washout phase, patients were randomly allocated to receive losartan 50 mg once daily, lisinopril 20 mg once daily, or placebo for a maximum of 8 weeks. The primary efficacy end point of the study was the presence or absence of dry cough during the double-masked period, as rated by the patient at each visit using a validated symptom assessment questionnaire. A secondary end point was the frequency of dry cough, as measured at each visit using a visual analogue scale (VAS). The incidence of dry cough was significantly higher in the lisinopril group than in the losartan and placebo groups (87.5% vs 36.7% and 31.4%, respectively) at the end of the double-masked treatment period; there was no statistically significant difference between the losartan and placebo groups. Mean VAS scores showed that patients treated with lisinopril rated themselves as having a significantly higher frequency of cough than did patients treated with losartan or placebo (4.0 vs 1.2 and 1.5, respectively). Again, the difference between the losartan and placebo groups was not statistically significant. All treatments were otherwise well tolerated, and no serious clinical or laboratory adverse events were reported during the double-masked phase of the study. These results demonstrate that the incidence, severity, and frequency of dry cough in patients with a history of ACE inhibitor-induced dry cough are significantly lower in those treated with losartan than in those treated with lisinopril and are similar to the incidence, severity, and frequency of dry cough in those receiving placebo.

Effects of losartan on a background of hydrochlorothiazide in patients with hypertension.

The purpose of this multicenter trial was to compare the antihypertensive efficacy and safety of losartan potassium (losartan), a selective angiotensin II receptor antagonist, when added to hydrochlorothiazide in hypertensive patients whose blood pressure was not adequately controlled by 25 mg hydrochlorothiazide monotherapy. After a 4-week monotherapy period of 25 mg hydrochlorothiazide, 304 patients with trough (22 to 26 hours postdose) sitting diastolic pressure between 93 and 120 mm Hg were maintained on 25 mg hydrochlorothiazide and randomized double-blind into treatment arms consisting of either 25, 50, or 100 mg losartan or placebo once daily for 12 weeks. The reductions in sitting diastolic pressure for patients treated with 25, 50, or 100 mg losartan concomitantly administered with 25 mg hydrochlorothiazide were significantly greater (P < or = .05) than the reductions observed in the 25 mg hydrochlorothiazide plus placebo group beginning 1 week after randomization. The antihypertensive response in all groups was greater at week 3 than week 1, with some additional decrease in blood pressure in some groups at later times. Sitting systolic pressures were also significantly reduced in each group over time. Standing blood pressures at week 12 were similar to sitting blood pressures. A dose-response relationship to losartan was observed in this patient population. The percentages of the total drug-related clinical adverse experiences as assessed by the investigator were generally similar in the 25, 50, and 100 mg losartan plus 25 mg hydrochlorothiazide groups (10.3%, 24.4%, and 20.0%, respectively) compared with the placebo plus 25 mg hydrochlorothiazide group (24.7%).(ABSTRACT TRUNCATED AT 250 WORDS)