Amlodipine versus chlorthalidone versus placebo in the treatment of stage I isolated systolic hypertension

Abstract

The study was to compare the effects of amlodipine (calcium channel antagonist), chlorthalidone (diuretic), and placebo in adults more than 50 years of age with stage 1 isolated systolic hypertension (ISH). After a 4-week placebo run-in phase, 150 patients were randomly assigned in a double-blind fashion to treatment with 5 mg of amlodipine (n = 48), 15 mg of chlorthalidone (n = 50), or placebo (n = 52). Patients who failed to meet the systolic blood pressure (BP) reduction goal by week 4 had their dose increased to 10 mg of amlodipine or 30 mg of chlorthalidone, and maintained at this increased dose for 12 weeks. Results showed a mean reduction (mean +/- SD) in sitting systolic BP from baseline to the last treatment visit of -14.6+/-12.2 mm Hg (95% confidence interval [CI] -18.2, -11.0), -14.0+/-13.46 mm Hg (95% CI -17.8, -10.2), and -3.4+/-11.83 mm Hg (95% CI -6.7, -0.1) for the amlodipine, chlorthalidone, and the placebo treatment groups, respectively. Both active treatments showed significantly greater reductions than the placebo group (P < or = .001), but were not significantly different from each other. Sixty-seven percent of the amlodipine, 69% of the chlorthalidone, and 25% of the placebo-treated patients reached the protocol defined systolic BP goal (P = .001). Both active treatment groups showed a trend of better systolic BP response in older patients (> or =65 years). Secondary efficacy measures including pulse pressure, standing systolic, diastolic, and the 24-h ambulatory BP were also statistically significantly improved for both active treatments at the end of treatment, except for chlorthalidone in standing diastolic BP. Adverse events that occurred during the study were as expected and were well tolerated. The results of this study support the efficacy and safety of amlodipine and chlorthalidone for the treatment of stage 1 ISH during 20 weeks of treatment.

Treatment of Hypertension in Older Patients: An Updated Look at the Role of Calcium Antagonists

“…In another recent study of the treatment of stage 1 ISH, 54 the efficacy and tolerability of amlodipine (5 mg) were compared with those of chlorthalidone (15 mg) and placebo in 150 older adults (mean age, 66 years). The dosage of study drug could be doubled after 4 weeks of treatment if the goal SBP (<140 mm Hg) was not reached; patients were then maintained at their designated increased dose for an additional 12 weeks.…”

All Thiazide‐Like Diuretics Are Not Chlorthalidone: Putting the ACCOMPLISH Study Into Perspective

“…Chlorthalidone more closely resembles amlodipine in its comparative pharmacokinetic profile, pharmacodynamic profile, and antihypertensive efficacy, with a half-life of 45 to 60 hours when used chronically. 22 This is believed to be due to significant partitioning into red blood cells and an ability to backleak into plasma and prevent the late period of antidiuresis (the ''braking'' effect). 23 Chlorthalidone and hydrochlorothiazide differ in potency; 14 this has direct implications on both dosing equivalence and kaluresis.…”

Stress Management Versus Lifestyle Modification on Systolic Hypertension and Medication Elimination: A Randomized Trial

“…Pharmacologic studies of stage 1 SH indicate that patients treated with placebo have reductions ranging from 2.0 30 to 3.4 31 mm Hg in SBP over 8 weeks. Studies of aerobic exercise versus normal sedentary activity report a modest (ϳ4 mm Hg) reduction in SBP, 32 and in the DASH trial 24 of conventional versus fruit/vegetable diets, patients achieved an average of 0.6 mm Hg and 3.8 mm Hg reduction in DBP and SBP reduction, respectively.…”