Overview of Clinical Safety and Efficacy of Tertatolol

Abstract

Tertalolol is a noncardioselective beta-blocker, devoid of intrinsic sympathomimetic activity. Its renal vasodilating properties have been demonstrated both in animals and in man. The beta-blocking activity of tertatolol was assessed on the reduction of heart rate at submaximal exercise. The oral dose of 5 mg was optimal, leading to a significant reduction of diastolic blood pressure throughout 24 h. The efficacy was confirmed in mid- and long-term studies. In mid-term, randomized controlled studies, versus beta-blockers, the antihypertensive efficacy of tertatolol 5 mg was comparable to that of acebutolol 400 mg but of earlier onset, and comparable to that of atenolol 100 mg. Its efficacy was confirmed in 3 long-term studies. In the first study, tertatolol 5 mg alone or combined with a diuretic and, if necessary, dihydralazine, controlled 93.6% of patients (supine DBP < 90 mm Hg). 72.7% of patients were controlled with tertatolol alone, 16.4% with tertatolol plus diuretic, and 4.5% with tertatolol plus diuretic and dihydralazine. In a second study, 88.5% of patients were controlled, 56.3% with tertatolol alone and 32.2% with tertatolol plus diuretic. In the third study, 88.8% of patients were controlled after 1 year treatment, 66.1% with tertatolol alone and 22.7% with tertatolol plus diuretic. The overall clinical safety was excellent: only 6.6% of the 2,706 patients treated for 1 year withdrew from the study because of side effects. In patients followed for 1 year, side effects were rare, transient and mostly of mild severity.Biochemical surveillance did not show any adverse metabolic effects of tertatolol. Conversely, in two long-term studies, creatinine and cholesterol levels decreased significantly. When administered to normo- and hyperli-pidemic hypertensive patients, tertatolol induced a moderate increase in triglyceride levels without any change in HDL-cholesterol levels or in the total cholesterol/HDL-cholesterol ratio. Tertatolol was also studied in hypertensive patients with risk factors. In patients with left ventricular hypertrophy, tertatolol 5 mg significantly improved the left ventricular anatomy and function by reducing the left ventricular mass index and the early-to-late ratio of the diastolic peak flow velocity across the mitral valve. In patients with chronic renal failure, a 3-month treatment with tertatolol 5 mg significantly increased the glomerular filtration rate and the effective renal plasma flow. Meanwhile, renal vascular resistance decreased and the filtration fraction remained unchanged.