Sex and age related antihypertensive effects of amlodipine - ACCT

Description:

The ACCT trial was a prospective, open-label multicenter trial designed to assess the safety and efficacy of once daily dose of amlodipine and whether there are age, sex or racial differences in response to amlodipine in patients with essential hypertension.

Hypothesis:

Amlodipine is safe and effective in the treatment of mild-moderate hypertension among diverse patient populations.

Study Design

Study Design:

Patients Enrolled: 1084
Mean Patient Age: mean age 55.5 years
Female: 35

Patient Populations:

Men and women age ≥21 years with mild to moderate hypertension, with two diastolic BP measurements between 95 to 110 mmHg at two separate occasions in consecutive weeks during the placebo phase.

Exclusions:

Women of childbearing age, lactating or pregnant women; secondary hypertension, cerebrovascular accident, myocardial infarction or transient ischemic attack during the preceding six months; angina requiring use if nitrates, b-blockers or calcium-channel blockers, EF<40% or NYHA >class II, second or third degree heart block, arrhythmias; major hematologic, renal (creatinine >2mg/dl), hepatic, metabolic, gastrointestinal or cardiac dysfunction; history of non-compliance with medications; patients requiring continued therapy with other agents used for hypertension; use of the study medication within a month of entering the study; known sensitivity to dihydropyridines calcium-channel blockers; body weight >40% from the ideal body weight.

Primary Endpoints:

Decrease in systolic and diastolic BP.

Secondary Endpoints:

Sex, age and racial difference in the blood pressure response to amlodipine.

Drug/Procedures Used:

The study consisted of four phases: 1) a two-week placebo run-in phase (phase I) during which all antihypertensive medication was discontinued, 2) a four-week titration/efficacy phase during which a once daily of 5mg to 10 mg amlodipine was administered (phase II), 3) a 12-week maintenance phase during which patients were maintained on their final phase-II dose (phase III) and 4) an optional long-term follow-up phase (phase IV).

Concomitant Medications:

Physicians were free to use whatever additional therapy was considered necessary for other medical comorbidities.

Principal Findings:

A total of 1084 patients completed the study and were included in the efficacy analysis. Among the 1084 evaluable patients, 65% were men and 35% were women, 79% were white and 21% were black, 75% were <65 years and 25% were >65 years. The mean doses of the study medication at the end of maintenance phase were 8.6±2.3 mg/day for men and 8.1±2.4 mg/day for women (p<0.01), 8.4±2.3 mg/day for whites and 8.6±2.3 for blacks, 8.6±2.3 mg/day for patients <65 years old and 8.1±2.4 for patients >65 years old (p<0.01). The percentage of patients achieving goal blood pressure response with amlodipine therapy was greater in women (91.4%) than in men (83%)(p<0.001) and in those aged >65 years (91.5%, n=382) than in those <65 years(84.3%, n=702)(p<0.01). Changes in blood pressure from baseline were significantly greater in women than in men (p<0.0001) and were still statistically different according to sex when data were adjusted for weight, age, baseline BP and dose (mg/kg). Changes in systolic blood pressure from baseline were significantly greater in blacks than in whites (p<0.01) but not in diastolic BP. These changes were not observed after adjustment for baseline differences. Furthermore, changes in systolic BP were greater in patients >65 years than in patients <65 years (p<0.001) but these differences were not noted after adjustment for baseline characteristics. Edema was the most frequent side effect, occurred in 24% of patients and more frequently in women.

Interpretation:

Among patients with mild to moderate hypertension, amlodipine was effective in decreasing blood pressure in a heterogeneous patient population. Furthermore, it was observed that the response rates and absolute decrease in blood pressure was greater in women than in men.

References:

Cloner RA, Sowrens RJ, DiBona JF, Gaffney M, Wein M. Sex and age related antihypertensive effects of amlodipine. AJC 1996;77:713-722.

Clinical Topics: Prevention, Hypertension

Keywords: European Continental Ancestry Group, Edema, Blood Pressure, Amlodipine, African Continental Ancestry Group, Hypertension, Calcium Channel Blockers


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