Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.

The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.

Candesartan cilexetil: comparison of once-daily versus twice-daily administration for systemic hypertension. Candesartan Cilexetil Study Investigators.

This randomized, double-masked, placebo-controlled, forced-titration, parallel-arm study was designed to compare the blood pressure (BP)-lowering effect of candesartan cilexetil, a potent antagonist of the angiotensin II receptor subtype AT1, administered once daily with that of the same agent administered twice daily at the same total daily dose of 16 mg. After a 4- to 5-week placebo run-in period, 277 patients with a sitting diastolic BP of 95 to 109 mm Hg were randomly allocated to receive placebo (n = 92) or candesartan cilexetil 8 mg once daily for 4 weeks, followed by forced titration to either 16 mg once daily (n = 91) or 8 mg twice daily (n = 94) for 4 weeks. At 8 weeks, mean reductions in trough sitting diastolic BP were similar for the once- and twice-daily treatment groups (9.4 and 10.3 mm Hg, respectively). After 8 weeks of treatment, no statistically significant differences were observed in diastolic or systolic BP, peak or trough BP, or sitting or standing BP between the 2 active-treatment groups. The rates of positive responses (defined as a trough sitting diastolic BP of <90 mm Hg or a decrease in BP of > or =10 mm Hg) were also similar (approximately 60%) in the once- and twice-daily candesartan cilexetil groups. Furthermore, placebo-corrected trough-to-peak ratios for sitting diastolic BP exceeded 75% for both candesartan cilexetil regimens, indicating a persistent 24-hour duration of drug effect. Ambulatory BP monitoring performed in a subset of patients (n = 44) confirmed the consistent 24-hour BP-lowering effect and preservation of diurnal variation with once-daily dosing. No significant between-group differences were observed in the incidence or severity of clinical or laboratory adverse events. The results of this study suggest that identical daily doses of candesartan cilexetil administered once or twice daily have comparable efficacy and tolerability and that no additional clinical benefit is derived from twice-daily administration.

Cytomegalovirus hepatitis mimicking an acute exacerbation of chronic hepatitis B.

We report the case of a 29-year-old woman who had acute cytomegalovirus hepatitis superimposed on previously unrecognized chronic hepatitis B infection. We then review the diagnostic approach to acute hepatitis and positive hepatitis B surface antigen.

Pseudohypertension.

The purpose of this review is to integrate information available regarding pseudohypertension. A MEDLINE search (1966 to December 1993) was conducted using the key words pseudohypertension and Osler's maneuver. All articles containing reference to pseudohypertension were selected and reviewed. Additional articles were obtained from the citations included within these articles. Quantitative information from each reference was reviewed to derive qualitative statements about new perspectives on the pathophysiology and evaluation of pseudohypertension. The prevalence of pseudohypertension is unknown but probably increases with advancing age. Diagnosis requires a high index of suspicion. Demographic information has not been shown to be useful for identifying patients with pseudohypertension. Symptoms of postural hypotension despite antihypertensive therapy, treatment-resistant hypertension, and the absence of end-organ effects in long-standing "hypertension" are clinical features that suggest pseudohypertension. Automatic infrasonic blood pressure measurements may offer more accurate estimates of intra-arterial blood pressure than indirect sphygmomanometry in patients with these clinical features.