Short- and long-term efficacy of a calcium-antagonistic agent (nifedipine) combined with methyldopa in the treatment of severe hypertension.

Abstract

Nifedipine induces a potent vasodilating and antihypertensive effect in man through a Ca-antagonistic action. The drug was tested alone and in combination with methyldopa in 23 subjects with uncomplicated primary severe hypertension (diastolic pressure > 120 mm Hg) in a short- and long-term therapeutic trial. Hourly pressure readings during the short-term period showed that the antihypertensive response to nifedipine (10 mg orally) is maximal within 40 min and lasts for 8-12 h. When nifedipine is administered every 6 h the tendency of blood pressure to rise after each dose is repressed by the next dose, so that pressure remains significantly reduced throughout the 24 h; when methyldopa is combined (250 mg 4 times daily) blood pressure is further reduced toward normal, without significant fluctuations during the day. After 10 days of drug combination, the antihypertensive response was mediated through reduction of peripheral vascular resistance associated with increase in cardiac output. Renal function was unchanged or improved and Na retention and plasma volume expansion were not promoted. In 6 patients with very severe hypertension (diastolic pressure > 140 mm Hg) complicated by cardiac failure a dosing regimen every 4 h of the 2 compounds promptly relieved dyspnea and lung congestion and, within 2-3 days, stabilized blood pressure to an average of 150/98 mm Hg. Persistence of the antihypertensive efficacy of this drug combination in a dosing regimen every 6 h and its beneficial effects on heart size, ECG and fundi were documented in 22 subjects (4 of whom belonged to the decompensated group) who completed a 12 mo. follow-up. A tendency in 7 cases to ankle pitting or edema was the major side effect of nifedipine; the cause of this effect remains obscure.