Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators.

The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.

Evaluating Health-related quality-of-life outcomes in patients with congestive heart failure. A review of recent randomised controlled trials.

Congestive heart failure (CHF) is a chronic disorder characterised by fatigue, shortness of breath and congestion. Treatment is designed to relieve symptoms, halt or delay progression of the disease, prolong life and, ultimately, improve quality of life. The purpose of this paper is to identify recent trends in the assessment of health-related quality-of-life (HR-QOL) outcomes in randomised, controlled trials evaluating treatment effectiveness in patients with CHF. 41 studies using HR-QOL as an explicit outcome and published in English between 1990 and September 1998 were reviewed. Trends in the measurement of HR-QOL and evidence of treatment effectiveness are presented followed by a discussion of the implications for future research. Results suggest that pharmacological and nonpharmacological treatment regimens can have a positive impact on HR-QOL. However, treatment-related improvement in exercise capacity in patients with CHF was not consistently associated with improvement in all domains of HR-QOL. The primary HR-QOL domain affected by treatment appears to be the performance of daily activities, which may or may not be accompanied by enhanced well-being. This suggests that functional status should be considered a primary HR-QOL end-point in clinical intervention trials. Preference-based or utility assessment, ethnic group differences in treatment effectiveness, caregiver burden and cost effectiveness are understudied outcomes in CHF research.

Hypertension and current issues in compliance and patient outcomes.

Economic and human costs associated with untreated or inadequately controlled hypertension and its complications continue to be an issue in the United States despite the availability of numerous antihypertensive agents. Knowledge of hypertension, product profiles, tolerability concerns, convenience of dosing, health-related quality of life effects, and cost of therapy are some of the factors that may influence the compliance of patients to their medication regimens. Recent reports on patient noncompliance have focused on patient-provider relationships, psychosocial barriers, home blood pressure monitoring, and electronic monitoring systems to improve blood pressure control. The use of health-related quality of life assessment in antihypertensive studies and in routine clinical practice provides another opportunity to optimize a patient's regimen for short- and long-term hypertension control in a cost-effective manner.

Effects of candesartan cilexetil on health-related quality of life in black patients with systemic hypertension in the ABC Trial.

Tolerability is an important consideration in evaluating a new antihypertensive agent. This can be assessed informally by conventional patient interviews or more formally with the use of validated health-related quality of life (HRQL) measures assessing the patient's perception of the agent's tolerability. HRQL was a secondary end point of a 12-week, multicenter, double-blind, randomized, placebo-controlled study of the efficacy and tolerability of candesartan cilexetil in black patients with systemic hypertension. HRQL was evaluated using the generic Medical Outcomes Study 36-Item Short Form (SF-36) and population- and condition-specific Vital Signs Quality of Life Questionnaire (VSQLQ). Data were gathered via face-to-face interviews at screening, baseline, and weeks 8 and 12. Of the 304 patients randomized, 268 were evaluable for the HRQL analysis. Clinical results, reported in the companion article, found that candesartan cilexetil initiated at 16 mg once daily and titrated to 32 mg once daily as needed, with the subsequent addition of hydrochlorothiazide 12.5 mg as needed, was effective for lowering diastolic and systolic blood pressure and was well tolerated based on office interviews. Analyses of patients' perceptions of tolerability found that HRQL was maintained during the 12-week study period, with no significant differences between treatment and placebo groups at the end of double-blind treatment. These results indicate that the HRQL of black patients with systemic hypertension is maintained during treatment with candesartan cilexetil.