This study assessed blood pressure (BP) reductions and response rates following addition of nebivolol to ongoing antihypertensive therapy in patients with uncontrolled stage I-II hypertension despite antihypertensive treatment. Patients with an average sitting diastolic BP (SiDBP) X90 and p109 mm Hg while taking an antihypertensive regimen were included in this double-blind, placebo-controlled, parallel-group study. The primary efficacy end point was reduction from baseline to week 12 in mean trough SiDBP. In total, 669 patients were randomized to once-daily nebivolol 5, 10 or 20 mg or placebo. Addition of nebivolol 5, 10 and 20 mg significantly reduced BP; placebo-subtracted least squares mean reductions in trough SiDBP were À3.3, À3.5 and À4.6 mm Hg, respectively (Po0.001) and À5.7, À3.7 and À6.2 mm Hg in trough sitting systolic BP (SiSBP), respectively (Pp0.015). Adding nebivolol 5-20 mg resulted in significantly more responders (SiDBP o90 or X10 mm Hg reduction; range: 53.0-65.1 vs 41.3% with placebo; Pp0.028) and significantly better control rates (SiSBP/ SiDBP o140/90 mm Hg; range: 41.3-52.7 vs 29.3% with placebo; Pp0.029). Nebivolol was well tolerated; the incidence of adverse events with nebivolol was similar to that with placebo (40.2 vs 38.9%, respectively; P ¼ 0.763). Addition of once-daily nebivolol to ongoing antihypertensive therapy provided significant additional BP reductions and better response rates in patients with uncontrolled hypertension and was well tolerated.

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SUMMARY The antiarrhythmic action of the beta-blocking drug, acebutolol, was evaluated in patients with frequent premature ventricular contractions (PVCs). In the 12 hours following administration of a single 300 mg oral dose, 8 of 10 patients showed a greater than 50% reduction in PVC frequency, and statistical analysis indicated that PVC reduction persisted for 10 hours after the single dose. Analysis of plasma concentrations of acebutolol and an acetyl metabolite indicated that after single oral doses the plasma concentrations of the metabolite exceed those of unchanged acebutolol.A POSITIVE CORRELATION between the presence of frequent premature ventricular contractions (PVCs) and the subsequent incidence of sudden cardiac death has been observed,1' 2 particularly in patients with coronary artery disease.8 3 It is a reasonable though unproven hypothesis that suppression of these ectopic impulses would result in a decrease in the incidence of sudden death in these patients. Testing of this hypothesis has been limited to date primarily by the lack of antiarrhythmic drugs suitable for chronic administration.6 7 Such drugs should be effective, free of toxicity, and have properties that allow administration on a convenient dosage schedule which permits patient compliance. The development of such agents is currently the goal of extensive laboratory and clinical investigation.Acebutolol, (M&B 17803A) (±)-1-(2-acetyl-4-n-butyramido-phenoxy)-2-hydroxy-3-isopropylaminopropane ( fig. 1) is a new, relatively cardioselective beta-adrenergic antagonist. Acebutolol blocks the myocardial beta-receptors by a competitive inhibition and has a weak sympathomimetic action.8 In intravenous studies, it has approximately one-seventh the beta-blocking potency of propranolol.9 In addition, it has the membrane-stabilizing, so-called "quinidine-like" property found in propranolol but not in practolol.'0 In experimental arrhythmia studies, differences from both propranolol and practolol have been noted1' which have potential clinical utility, and preliminary clinical arrhythmia studies are promising.'2 The drug has less effect on the beta-receptors of bronchial smooth muscle than propranolol and has been administered to asthmatics.'8 Acebutolol has also been used successfully in When patients were studied during periods of 300 mg doses every 8 hours, eight of 11 showed a 70% reduction in PVC frequency, and analysis showed that the therapeutic effect was present throughout the 24-hour monitoring period. Acebutolol slowed the heart rate and prolonged the PR interval without affecting the QT interval. Significant clinical or laboratory toxicity was not encountered. In the small group studied, acebutolol was found to be safe and effective for shortterm administration to patients with frequent PVCs and possessed a relatively long duration of antiarrhythmic action.of acebutolol to a group of ambulatory patients with frequent PVCs. Methods Patient PopulationTwelve patients, 11 men and one woman, participated in the study after giving written...

A man with known coronary heart disease underwent treadmill exercise testing to determine his functional capacity. The test was negative for ischemia. Ventricular ectopic activity was noted at rest and in the recovery period. On the same day, while viewing a sporting event at home, the patient died suddenly. An ambulatory electrocardiographic recording documented ventricular fibrillations as the terminal mechanism. Ventricular ectopic activity and heart rate increased in the two hours prior to death, and ischemic ST-segment depression was noted at the time of the terminal arrhythmia. It is postulated that myocardial ischemia and catecholamine response lowered the threshold to ventricular fibrillation, thus facilitating the emergence of the fatal arrhythmia.

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