Metoprolol and propranolol in the treatment of essential hypertension - a long-term comparative study.

After a two-week run-in period on placebo, fifty-two patients with benign essential hypertension (WHO classes I or II) were treated with individually titrated doses of metoprolol or propranolol for 36 weeks. If blood pressure was not satisfactorily controlled by beta-blockers, a saluretic diuretic and, if necessary, hydralazine were added. Five patients on metoprolol and four on propranolol received such additional therapy. Fifty patients completed the trial. The final mean daily doses of metoprolol and propranolol were 327 mg and 282 mg, respectively. As the beta1-adrenoceptor-blocker potency of the drugs is 4:5 (i.e. 50 mg metoprolol corresponds to 40 mg propranolol in reducing exercise-induced tachycardia) the relative dose of metoprolol seemed to be slightly lower than that of propranolol. Compared to the values during the placebo period, heart rate, systolic and diastolic blood pressure in both the supine and standing position were significantly reduced in both groups after 12, 24 and 36 weeks' treatment with active drug. At the end of the treatment period, the mean reductions in supine blood pressure were 26/15 and 16/9 mm Hg in the metoprolol and propranolol groups, respectively. The reductions in supine diastolic and standing systolic blood pressures were significantly greater in the metoprolol than the propranolol group at this time.

Pafenolol in hypertension: a double-blind randomized trial of a new beta 1-selective adrenoceptor blocker.

The antihypertensive effect of pafenolol, a new beta 1-selective adrenoceptor blocker without intrinsic sympathomimetic activity and three times more selective than metoprolol, was evaluated. Twenty-three patients with essential hypertension, mean age 49 years (range 21-62), were randomized after a 4-week placebo run-in period (double-blind) to 4 weeks of either placebo, pafenolol 50 mg or 100 mg once daily. A submaximal exercise test was performed before and at the end of the treatment period. Pafenolol 50 mg and 100 mg significantly reduced recumbent and standing blood pressure compared with baseline with a mean reduction of 17/14 and 10/12 mm Hg on pafenolol 50 mg and 15/10 and 14/10 mm Hg on pafenolol 100 mg, respectively. Heart rate, both at rest and during exercise, was significantly reduced (p less than 0.05) on pafenolol 100 mg compared with placebo. The reduction in exercise heart rate (percent) was dose dependent and significantly correlated to the log plasma concentration of pafenolol (r = 0.60; p less than 0.05). It can be concluded that pafenolol had a clinically relevant antihypertensive effect when given once daily. No difference between 50 and 100 mg could be demonstrated, thus suggesting that 50 mg may be the preferred dose for antihypertensive treatment.

Short-term effects of felodipine, a new dihydropyridine, in hypertension.

Felodipine, a dihydropyridine, is a new vasodilating calcium antagonist which lowers blood pressure (BP) by selective action on vascular smooth muscle, especially in the resistance vessels. The effects on BP, heart rate (HR) and tolerance of different single oral doses of felodipine were studied in two series of hypertensive patients. When felodipine was given as single drug to 14 previously untreated hypertensives in a single-blind manner, BP was rapidly reduced by about 15% while HR increased by 25%. Felodipine given in a double-blind manner to eight patients on chronic beta-adrenoceptor blockade reduced BP by some 15-20% compared to placebo, while HR did not change. There was a significant correlation between the pre-treatment mean arterial BP (MAP) and the maximal relative change in MAP, i.e. the higher the initial BP the greater the reduction after felodipine. A significant correlation was also found between the plasma concentration of felodipine and the relative change in MAP. Felodipine was generally well tolerated. When given alone felodipine caused the side effects expected from a pure vasodilator, i.e. headache, flushing and palpitations. When given together with a beta-adrenoceptor blocker, the side effects were much less apparent.