Improvement in exercise tolerance and symptoms of congestive heart failure during treatment with candesartan cilexetil. Symptom, Tolerability, Response to Exercise Trial of Candesartan Cilexetil in Heart Failure (STRETCH) Investigators.

BACKGROUND: The renin-angiotensin system plays an important part in the pathogenesis of congestive heart failure (CHF). This study evaluated the effect of an angiotensin II type 1 receptor antagonist on exercise tolerance and symptoms of CHF. METHODS AND RESULTS: In this multicenter, double-blind, parallel-group study, 844 patients with CHF were randomized to 12 weeks' treatment with placebo (n=211) or candesartan cilexetil 4 mg (n=208), 8 mg (n=212), or 16 mg (n=213) after a 4-week placebo run-in period. Changes in exercise time, Dyspnea Fatigue Index score, NYHA functional class, and cardiothoracic ratio were determined. Candesartan cilexetil produced a dose-related improvement in exercise time. For the intention-to-treat population, the increase produced by candesartan cilexetil 16 mg was significantly greater than that produced by placebo (47.2 versus 30.8 seconds, P=0.0463). All doses of candesartan cilexetil significantly improved the Dyspnea Fatigue Index score relative to placebo. NYHA class improved more frequently in the candesartan cilexetil groups; the differences relative to placebo were not significant. The decrease in cardiothoracic ratio with candesartan 4 to 16 mg was small but statistically significant compared with placebo (all P<0.05). In all candesartan cilexetil groups, plasma renin activity and angiotensin II levels increased from baseline and aldosterone levels decreased in the 8- and 16-mg treatment groups. Candesartan cilexetil was well tolerated at all doses. CONCLUSIONS: In summary, treatment with candesartan cilexetil demonstrated significant improvements in exercise tolerance, cardiothoracic ratio, and symptoms and signs of CHF and was well tolerated.

Prokinetic drug treatment (cisapride) is as effective as H2-blocking agent (ranitidine) in the treatment of gastric ulcer.

A double-blind, randomized, parallel-group multicenter study was conducted in 120 patients with gastric ulcer to compare cisapride, 10 mg t.i.d., and ranitidine, 150 mg b.i.d., administered over 8 weeks. No significant differences between the results of the two treatments were found in terms of ulcer healing or symptomatic relief. Endoscopy showed that the incidence of medium-sized or large ulcers was reduced from 85% at the start to 11% and 4%, respectively, after 4 and 8 weeks in the ranitidine group, and from 98% to 15% and 4%, respectively, in the cisapride group. By week 8, the ulcer was healed in 89% of the ranitidine patients, and in 86% of the cisapride patients. Moderate to severe diurnal epigastric pain--the predominant symptom--was reported by about 80% of the patients in week 8, and by less than 15% from week 4 on. The response to nocturnal epigastric pain, epigastric pressure, sensation of fullness and other symptoms was similar. Except for gastrointestinal symptoms in the cisapride patients--nearly always indicative of enhanced bowel contractions--the occurrence of adverse effects was similar in the two groups. The improvement in gastrointestinal motility under cisapride, would appear to be as effective as suppression of acid secretion in the treatment of gastric ulcer disease.

A double-blind comparative study of doxazosin and nitrendipine in patients with mild-to-moderate essential hypertension.

The antihypertensive efficacy and safety of doxazosin, a selective alpha 1-inhibitor, were compared with nitrendipine. Seventy-two hypertensive patients were entered into the 18-week, double-blind parallel group study, which involved three phases: a 4-week baseline period, a 10-week period in which patients received 1 to 8 mg of doxazosin or 10 and 20 mg of nitrendipine once daily, and a 4-week maintenance period. For all patients, the mean final daily doses were 2.5 mg for doxazosin and 13.9 mg for nitrendipine. In efficacy evaluable patients the percentages of therapy successes (standing diastolic blood pressure less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction or greater than or equal to 10 mm Hg decrease) were comparable for doxazosin (94%) and nitrendipine (91%), as was the proportion in whom blood pressure was "normalized" (standing diastolic blood pressure less than or equal to 90 mm Hg), 91% and 85, respectively. Blood pressures (diastolic and systolic in supine and standing positions) were significantly reduced (p less than 0.05) at all visits in both treatment groups. Ten patients (28%) in each treatment group experienced at least one adverse event. No clinically significant laboratory changes were apparent in either the doxazosin or nitrendipine groups, and no trends were observed with regard to organ systems or correlations with dose or duration of treatments. The investigators' global assessment of efficacy was rated excellent or good for all doxazosin-treated patients and excellent or good for 32 and fair for four in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS)