Labetalol therapy in patients with systemic hypertension and angina pectoris: effects of combined alpha and beta adrenoceptor blockade

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The effects of oral labetalol, an alpha-beta adrenoceptor blocker, were evaluated in 10 patients with angina pectoris and hypertension. After 3 weeks of placebo, increasing doses of labetalol (300 to 1,200 mg/day) were given over 4 weeks followed by a rapid drug withdrawal phase. The frequency of anginal attacks and exercise tolerance were measured as were noninvasive indexes of left ventricular function (echocardiography, systolic time intervals), plasma renin activity and platelet function (aggregability). Compared with placebo, during labetalol therapy the frequency of anginal attacks was reduced, exercise time increased (from 351.6 ± 56.2 to 463.2 ± 45.2 seconds, P < 0.005) and exercise work increased (from 3,470 ± 910 to 4,920 ± 1,020 kilopond- meters, p < 0.01). Labetalol (mean dose 1,050 mg/day) reduced resting supine and standing blood pressures and heart rate in all patients: supine systolic pressure from 166.5 ± 6.3 to 142.2 ± 4.9 mm Hg (mean ± Standard error of the mean) (p < 0.01), supine diastolic blood pressure from 102.7 ± 2.6 to 87.7 ± 1.5 mm Hg (p < 0.01), supine heart rate from 80.8 ± 4.6 to 65.6 ± 2.3 beats/ min (p < 0.05), standing systolic blood pressure from 156.8 ± 4.2 to 127.5 ± 5.3 mm Hg (p < 0.01), standing diastolic blood pressure from 101.4 ± 2.3 to 83.9 ± 3.0 mm Hg (P < 0.01) and standing heart rate from 81.5 ± 4.9 to 69.0 ± 2.8 beats/ min (p < 0.01). The increments in systolic blood pressure with exercise were significantly blunted; those for heart rate were not affected. There was a significant reduction in resting heart rate-blood pressure product and an inhibition of heart rate-blood pressure increments with exercise. Compared with placebo, labetalol had no effects on platelet function or on resting noninvasive indexes of left ventricular function. The three patients with elevated plasma renin activity demonstrated a marked reduction after labetalol; the seven patients with normal or low plasma renin activity were not affected by labetalol. No “rebound” effects were seen after withdrawal of labetalol. Combined alpha and beta adrenergic blockade with labetalol is effective for relieving anginal symptoms, improving exercise tolerance and reducing elevated systemic blood pressure.