CLINICAL-RESULTS OF THE VERAPAMIL IN HYPERTENSION AND ATHEROSCLEROSISSTUDY

Objective The Verapamil in Hypertension and Atherosclerosis Study (VHA S) is a prospective randomized study the objective of which was to com pare the long-term effects of verapamil and chlorthalidone on the bloo d pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patient s. Design After a 3-week placebo run-in period, 1414 hypertensive pati ents [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 d esign was double blind for the first 6 months and open thereafter. 25- 50 mg/day captopril were added to the treatment of non-responding pati ents; subsequently, patients not responding to combined therapy were s witched 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 thr oughout the study. Results After 2 years the systolic and diastolic bl ood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthali done, both by analysis of variance, P < 0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 2 6.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalizat ion of the diastolic blood pressure (to less than or equal to 90 mmHg or to less than or equal to 95 mmHg with a greater than or equal to 10 % decrease) was achieved for 69.3% of the verapamil and 66.9% of the c hlorthalidone group. A decrease in heart rate (by 5.8%) occurred in me mbers of the verapamil group only. A decrease in total serum cholester ol (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%) a nd 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). Ad verse 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 to tal 315 dropped out (153 from the verapamil and 162 from the chlorthal idone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS ). Conclusion Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlor thalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.