Related Experiment Videos
Clinical results of the Verapamil inHypertension and Atherosclerosis Study. VHAS Investigators
E A Rosei1, C Dal Palù, G Leonetti
1Cattedra di Semeiotica e Metodologia Medica, University of Brescia, Italy.
Insights
Verapamil and chlorthalidone demonstrated similar effectiveness in lowering blood pressure and similar cardiovascular event rates. However, chlorthalidone was linked to higher rates of hyperuricemia and hypokalemia compared to verapamil.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Hypertension is a major risk factor for cardiovascular disease.
- Long-term management of hypertension requires effective and safe antihypertensive medications.
- Atherosclerosis progression is a key concern in hypertensive patients.
Purpose of the Study:
- To compare the long-term effects of verapamil and chlorthalidone in hypertensive patients.
- To assess impacts on blood pressure, clinical safety, and carotid atherosclerosis.
- To evaluate efficacy and tolerability in a large patient cohort.
Main Methods:
- Prospective randomized study of 1414 hypertensive patients over 2 years.
- Comparison of sustained-release verapamil (240 mg) versus chlorthalidone (25 mg) daily.
- Double-blind for 6 months, then open-label with add-on therapies as needed.
Main Results:
- Both verapamil and chlorthalidone significantly reduced systolic and diastolic blood pressure.
- Similar rates of diastolic blood pressure normalization were achieved (69.3% vs. 66.9%).
- Chlorthalidone showed higher incidences of hyperuricemia (10.8% vs. 3.9%) and hypokalemia (24.6% vs. 4.4%) than verapamil.
Conclusions:
- Verapamil and chlorthalidone exhibit comparable antihypertensive efficacy and cardiovascular safety.
- Chlorthalidone is associated with a greater risk of metabolic disturbances like hyperuricemia and hypokalemia.
- Verapamil may offer a more favorable metabolic profile in hypertensive patients.
Objective:
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.
Design:
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.
Results:
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 < or = 90 mmHg or to < or = 95 mmHg with a > or = 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).
Conclusion:
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.