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Fixed-dose combination tablets, such as diuretic plus beta-adrenergic blocking drug or ACE inhibitor are more effective than is any monotherapy. Other advantages include simple titration, low toxicity and reduced expense which encourage better compliance required for optimal blood pressure control.

Background: Concern based on the reported short-term adverse effects of antihypertensive agents on plasma lipid and lipoprotein profiles (PLPPs) has complicated the therapy for hypertension., Objective: To compare the long-term (1-year) effects of 6 different antihypertensive drugs and placebo on PLPPs in a multicenter, randomized, double-blind, parallel-group clinical trial in 15 US Veterans Affairs medical centers., Patients and Methods: A total of 1292 ambulatory men, 21 years or older, with diastolic blood pressures (DBPs) ranging from 95 to 109 mm Hg taking placebo were randomized to receive placebo or 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, or prazosin. After drug titration, patients with a DBP of less than 90 mm Hg were followed up for 1 year. Plasma lipids and lipoprotein profiles were determined at baseline, after initial titration, and at 1 year., Results: After 8 weeks on a regimen of hydrochlorothiazide, increases of 3.3 mg/dL (0.09 mmol/L) in total cholesterol and 2.7 mg/dL in apolipoprotein B were significantly different (P< or =.05) from decreases of 9.3 mg/dL in total cholesterol and 5.4 mg/dL in ApoB levels while receiving prazosin but not from placebo. Patients achieving positive DBP control using hydrochlorothiazide (responders) showed no adverse changes in PLPPs, whereas nonresponders exhibited increases in triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. Plasma lipids and lipoprotein profiles did not change significantly among treatment groups after 1 year except for minor decreases in high-density lipoprotein 2 levels using hydrochlorothiazide, clonidine, and atenolol., Conclusions: None of these 6 antihypertensive drugs has any long-term adverse effects on PLPPs and, therefore, may be safely prescribed. Previously reported short-term adverse effects from using hydrochlorothiazide are limited to nonresponders.

A series of studies on various therapeutic aspects of beta-adrenergic-blocking drugs was carried out by the Veterans Administration Cooperative Study Group on Antihypertensive Agents. In one study the diastolic blood pressures of 49% of 132 men with mild to moderate hypertension were controlled (less than 90 mm Hg) with once-daily nadolol. In a similar group, 85% were controlled with nadolol plus bendroflumethiazide, both given once daily. Nadolol alone was as effective as diuretic alone, although in another study comparing propranolol and hydrochlorothiazide, the latter was somewhat more effective. In both trials black patients tended to respond better to the diuretic, whereas white patients responded better to the beta blocker. Although high-renin hypertensive patients tended to respond better to the beta blocker and low-renin patients to the diuretic, the relationships were not close enough to provide a dependable guide to treatment. Sixty percent of patients whose blood pressure was not controlled on the nadolol-containing regimens reached goal blood pressure (less than 90 mm Hg) with the addition of hydralazine, 25 to 100 mg twice daily.

1. The results of the Veterans Administration Co-operative Study have been extended by the subsequent clinical trials, which included patients of both sexes and with less vascular disease. The later studies confirm the effectiveness of treatment in preventing most complications except myocardial infarction and sudden death. Furthermore, the lower diastolic blood pressure in which treatment has been shown to have a significant beneficial effect has been lowered from 105 mmHg as indicated by the Veterans Study to 100 mmHg as shown by the much larger Australian trial. The possibility of reducing the incidence of sudden death and fatal myocardial infarction has been suggested by other recent control trials using beta-adrenoreceptor-blocking drugs, an approach that needs further exploration. 2. A number of interesting and useful new drugs have appeared which include tienilic acid, minoxidil, saralasin and captopril, and in addition recent controlled trials have re-emphasized the effectiveness of the old drug, reserpine, when combined with a diuretic. The art of treatment of hypertension therefore appears to be in a healthy state and we should expect more advances in the future.