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.

Synergistic effects of hydralazine and alpha- or beta-adrenergic blockers: the role of plasma renin activity.

Intravenous hydralazine, 0.15, 0.30 or 0.60 mg/kg, was administered to 11 supine hypertensives on two occasions: once after pretreatment with intravenous propranolol, 0.1 mg/kg, and once after pretreatment with intravenous placebo. The average fall in mean arterial pressure for each dosage of hydralazine was no different with or without propranolol, even though propranolol inhibited rises in plasma renin activity and pulse due to hydralazine. However, in each of four patients who had high supine baseline plasma renin activity, propranolol enhanced the fall in blood pressure caused by hydralazine. A second group of patients was given an infusion of 0.01 or 0.02 mg/kg per minute phentolamine, which did not change baseline blood pressure. Subsequent administration of intravenous hydralazine, 0.15 mg/kg, resulted in a fall in blood pressure which was larger than previously observed with intravenous hydralazine alone, regardless of supine baseline plasma renin activity. These data are consistent with the hypothesis that reflex catecholamine release interferes with the hypotensive effect of intravenous hydralazine. Pretreating with propranolol weakens homeostatic defenses against hydralazine such as rises in pulse rate and plasma renin activity. However, propranolol appears to enhance the alpha-adrenergic effect of released catecholamines, and the antihypertensive response to hydralazine is unaltered. In patients with high supine plasma renin activity, propranolol potentiates the fall in blood pressure induced by hydralazine, perhaps because the hypertension in such patients is renin dependent.