The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients.
After a 3-week placebo run-in period, 1414 hypertensive patients [692 men and 722 women, aged 53.2 ± 7 years, blood pressure 168.9 ± 10.5/ 102.2 ± 5.0 mmHg (means ± SD)] were assigned randomly to be administered either 240 mg sustained- release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25–50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study.
After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P < 0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to ≤ 90 mmHg or to ≤ 95 mmHg with a ≥ 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P < 0.01) and in the total cholesterol : high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P < 0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K < 3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P < 0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS).
Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.
1Cattedra di Semeiotica e Metodologia Medica, University of Brescia
2Istituto di Medicina Clinica, University of Padova
3Cattedra di Semeiotica e Metodologia Medica, University of Milan and the Istituto Scientifico San Luca, IRCCS Centro Auxologico Italiano, Milan
4Istituto di Malattie Cardiovascolari, University of Bologna
5Centro di Fisiologia Clinica e Ipertensione, Istituto di Clinica Medica, University of Milan and the IRCCS Ospedale Maggiore, Milan, Italy.
6Requests for reprints to Professor Alberto Zanchetti, Centro di Fisiologia Clinica e Ipertensione Ospedale Maggiore, Via F. Sforza, 35, 20122 Milano, Italy.
Received 26 May 1997 Revised 14 July 1997 Accepted 25 July 1997