Clinical Results of the Verapamil in Hypertension and Atherosclerosis Study - VHAS
This was a multicenter, randomized, double-blind parallel-group trial designed to compare the efficacy and safety of prolonged treatment with slow-release verapamil versus chlorthalidone among patients with essential hypertension.
Treatment of essential hypertension with slow-release verapamil would result in more effective control of blood pressure than with chlorthalidone.
Patients Screened: 7,839
Patients Enrolled: 1,414
Mean Follow Up: Two years
Mean Patient Age: 40-65 years
Systolic blood pressure ≥160 mm Hg, diastolic blood pressure ≥95, and age 40-65 years
Secondary hypertension, cerebrovascular event or acute coronary syndrome within six months, severe peripheral artery disease, heart rate <50 bpm, sick sinus syndrome, heart failure, serum creatinine >1.7 mg/dl, hepatic insufficiency, hyperuricemia, hypokalemia, type I diabetes mellitus or uncontrolled type II diabetes mellitus, or use of any other antihypertensive agent
Decrease in blood pressure (diastolic blood pressure ≤90 mm Hg or ≤95 mm Hg with a reduction of at least 10% from baseline values)
Cardiovascular events (myocardial infarction, stroke, transient ischemic attack, angina, chronic heart failure, claudication, revascularization procedures, and cardiovascular deaths)
Subjects were administered 240 mg slow-release verapamil or 25 mg chlorthalidone once a day for two years. After one month on study treatment, captopril was added in escalating doses if needed to reach blood pressure goals. After six months, treatment allocation was unblinded, but study medications were continued for a total of 24 months. Subjects were classified as nonresponders if blood pressure goals were not reached on the study drug and captopril. These patients were withdrawn from randomized treatment and were treated at their physicians' discretion, but were included in follow-up data on an intention-to-treat basis.
Captopril (23% in the verapamil group and 26% in the chlorthalidone group)
1,414 patients were enrolled in the study. Baseline characteristics of both study groups were similar: Mean systolic and diastolic blood pressures were 169 mm Hg and 102 mm Hg, and mean duration of hypertension was five years.
A total of 1,099 patients completed the two-year treatment period. The primary cause of study discontinuation was poor compliance.
On intention-to-treat analysis, treatment with both verapamil and chlorthalidone was associated with a significant decrease in blood pressure (-27.6/17 mm Hg with verapamil and -28.6/16.6 mm Hg with chlorthalidone, p<0.01 for both groups vs. baseline). There was no significant difference between the two groups.
Forty-four percent of patients treated with verapamil and 38.8% treated with chlorthalidone remained on monotherapy at 24 months (p<0.05); 11.6% of patients in the verapamil group and 12.2% of patients in the chlorthalidone group (p=NS) were classified as nonresponders and were shifted to therapy at their physicians' discretion. The total number of cardiovascular events was similar in each group (6% fatal and nonfatal events in each group).
Both medications were well tolerated, and adverse events led to discontinuation of study medication in 18 patients in each group. Treatment with verapamil was associated with a significant decrease in total cholesterol (-6.7 mg/dl, p<0.01 vs. baseline and vs. chlorthalidone group). Incidence of mild hypokalemia and hyperuricemia was associated with treatment with chlorthalidone.
Among patients with essential hypertension, treatment with sustained-release verapamil or chlorthalidone was associated with similar antihypertensive efficacy, tolerability, and cardiovascular event rates. Significantly more patients assigned to verapamil therapy remained on antihypertensive monotherapy through two-year follow-up.
Rosei EA, Dal Palu C, Leonetti G, Magnani B, Pessina A, Zanchetti A. Clinical results of the Verapamil in Hypertension and Atherosclerosis Study. VHAS Investigators. J Hypertens 1997;15:1337-44.
Keywords: Cholesterol, Hyperuricemia, Follow-Up Studies, Chlorthalidone, Hypokalemia, Verapamil, Blood Pressure Determination, Captopril, Hypertension, Systole, Calcium Channel Blockers
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