Effects of reduction in drugs or dosage after long-term control of systemic hypertension.

The possibility of discontinuing--compared to reducing--antihypertensive drug treatment was investigated in 606 male hypertensive patients with entry diastolic blood pressure (BP) in the range of 90 to 114 mm Hg. Diastolic BP was controlled at less than 90 mm Hg with 1 of 4 regimens: low dose hydrochlorothiazide (HCTZ), 25 mg twice daily; high dose HCTZ, 50 mg twice daily; or high dose HCTZ plus a low or high dose of a step II drug (propranolol, clonidine or reserpine). After 6 months of treatment that controlled BP, dosages were reduced in two-thirds of the patients. In those patients receiving low dose HCTZ and randomized to dose reduction, antihypertensive drugs were completely discontinued. Although approximately half of these patients remained normotensive for the first 6 months, a significantly greater proportion had elevation of BP compared to the control group, which continued to receive treatment (p less than 0.0001). In the high dose HCTZ drug group, the proportion of patients remaining normotensive did not differ among those stepped down to low dose HCTZ and the fully treated control group. While not achieving significance the trend was similar with the step II regimens. Although some patients remained normotensive after discontinuation of step II drugs, a greater proportion returned to elevated BP than when step II dosage was unchanged. Therefore, while stopping therapy may be effective in some patients, a decreased dosage is significantly more effective as a method for maintaining an antihypertensive effect. Decreasing drug dosages offers the dual benefit of minimizing side effects and reducing drug costs.

Reducing costs and improving compliance.

The cost-effectiveness of antihypertensive therapy is defined as the costs of treatment less the savings from the prevention of stroke and myocardial infarction, relative to the therapeutic effectiveness of treatment. Since antihypertensive therapy actually increases the dollar cost of medical care, the use of more expensive agents needs to be justified in terms of better blood pressure control, improved quality of life, and reduced cardiovascular morbidity and mortality. Data from the clinical trials have not shown the more expensive agents such as angiotensin-converting enzyme inhibitors and calcium channel blockers to be superior to the less expensive agents such as diuretic drugs in reducing blood pressure or cardiovascular morbidity and mortality. Poor compliance may reduce both the effectiveness and cost-effectiveness of treatment. Physicians must play an active role in prompting compliance by assuring the patient's ability to incorporate the prescribed dosage regimen into daily routine, by actively monitoring compliance, by modifying the regimen appropriately to remove the cause of noncompliance, and by switching medication if it is ineffective or if adverse effects occur.

Single and combined therapy for systemic hypertension with propranolol, hydralazine and hydrochlorothiazide: hemodynamic and neuroendocrine mechanisms of action.

The antihypertensive mechanisms of single and combined therapy with a beta-adrenergic antagonist (propranolol) and a vasodilator (hydralazine) were investigated in 9 patients with moderately severe hypertension, who were receiving maintenance diuretic (hydrochlorothiazide) treatment. Hemodynamic and neuroendocrine responses were determined at rest and during lower body negative pressure, and dynamic and static exercise stress after the chronic administration of propranolol and hydralazine, given alone or in combination. All 3 drug regimens, each administered for at least 10 weeks, reduced blood pressure (p less than 0.05) compared with diuretic-only therapy in patients at rest, in both the supine and standing position, and during lower body negative pressure and dynamic exercise. There was a significant additive antihypertensive effect when propranolol and hydralazine were combined. Only combination therapy effectively lowered pressure during static exercise. The regimens produced divergent effects on the supine cardiac output: a decrease with propranolol (p less than 0.05), no change with combination therapy and an increase with hydralazine (p less than 0.05). Both hydralazine and combination therapy significantly reduced supine total peripheral resistance (p less than 0.05), whereas propranolol produced no change. All 3 drug treatments significantly reduced total peripheral resistance during upright rest and dynamic exercise (p less than 0.05), without changing cardiac output or maximal exercise capacity. During exercise, cardiac output was maintained in patients treated with propranolol and in those treated with combined therapy by increases in stroke volume (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)