Effects of intravenous dofetilide in patients with frequent premature ventricular contractions: a clinical trial.

Background: Although suppression of premature ventricular contractions (PVCs) is not a predictor of mortality over the long term, the extent of PVC suppression is an important characteristic of any antiarrhythmic drug.

Hypothesis: This study was undertaken to determine whether intravenous (i.v.

Does Chinese ethnicity affect the pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors?

Information from clinical and pharmacokinetic studies of angiotensin-converting enzyme inhibitors (ACEIs) has come from subjects who are mostly male and Caucasian, but the use of ACEIs extends to populations worldwide. Significant differences between Chinese in general and male Caucasians have been demonstrated in the pharmacokinetics/dynamics of other drug classes that could have implications for the use of ACEIs in the Chinese population. These include: significant Chinese/Caucasian genetic variation in the renin-angiotensin system based on an insertion/deletion (O/D) polymorphism of the ACE gene; the genetic determination of plasma ACE activity in the Chinese population; and genetic factors involving the disease substrate which may also influence the response to treatment.

Anomalies in the dosing of diltiazem.

From early research, investigators understood that the dose of diltiazem required for the treatment of hypertension (commonly 360 mg/day) was greater than that required for the treatment of angina (commonly 240 mg/day). Nonetheless, studies of recent prescribing practices show that the 240 and 180 mg capsule strengths constitute more than 70% of the diltiazem prescriptions for hypertension. Physicians became accustomed to the lower antianginal doses of diltiazem for 7 years before a hypertension indication was approved.

Neurohormonal activation in the treatment of congestive heart failure: basis for new treatments?

Traditionally, the pathophysiology of heart failure was viewed as a derangement in hemodynamic factors. Impairment in cardiac function resulted in decreased cardiac output and end-organ hypoperfusion triggering compensatory increases in heart rate, blood pressure and cardiac contractility. While initially beneficial, these mechanisms placed additional stress on the failing heart.

Effect of morning versus evening dosing of diltiazem on myocardial ischemia detected by ambulatory electrocardiographic monitoring in chronic stable angina pectoris. Dilacor XR Ambulatory Ischemia Study Group.

Myocardial ischemia occurs frequently during daily life and has a circadian pattern similar to that reported for myocardial infarction and sudden death. Because of the increased risk of myocardial ischemia in the morning hours, it has been suggested that the administration of anti-ischemic medication before bedtime may be more effective than the traditional morning dosing. This randomized, double-blind, placebo-controlled, crossover study evaluated the effects of 480-mg/day diltiazem (given either in the A.

The clinical significance of neurohormonal activation.

Progressive heart disease after the onset of left ventricular dysfunction has typically been attributed to hemodynamic factors. As left ventricular function declines, decreased cardiac output and tissue hypoperfusion lead to compensatory increases in afterload, preload, and heart rate. The purpose of these compensatory responses is to increase cardiac output and maintain tissue perfusion; however, they may also create hemodynamic stress for the failing heart.

Arbutamine vs. exercise stress testing in patients with coronary artery disease: evaluation by echocardiography and electrocardiography.

Arbutamine is a new beta-adrenergic agonist with potent chronotropic and inotropic properties developed to pharmacologically induce stress. A prospective trial was conducted in five centers with a total enrolment of 45 patients with angiographically documented coronary artery disease. The primary purpose of the trial was to compare the efficacy of arbutamine with symptom-limited exercise in provoking clinical (angina), electrocardiographic (> or = 0.

The X-Ray CCDs Developed for the Joint European X-Ray Telescope.

The charge coupled devices (CCDs) developed for the Joint European X-ray Telescope (JET-X) are described in detail. A history of the development program and device performance is given. We present results from a comprehensive study to characterize the x-ray response of the flight model focal plane detectors.

Stress testing with closed-loop arbutamine as an alternative to exercise. The International Arbutamine Study Group.

Objectives: This study compared exercise and pharmacologic stress testing using arbutamine delivered by a closed-loop device for the detection of coronary artery disease.

Background: Arbutamine, an agent designed to simulate exercise, has been developed in conjunction with a closed-loop delivery device that modulates the rate of administration on the basis of physiologic feedback.

Methods: Two hundred ten patients (180 men, 30 women) with symptoms and angiographic evidence of coronary artery disease were studied.

Conversion from immediate-release to extended-release diltiazem in angina pectoris.

This multicenter, open-label, single crossover study examined 195 patients taking an immediate-release diltiazem tablet as chronic stable angina therapy to determine if apparently logical methods of converting them to an extended-release, once-daily formulation were effective. Patients were converted from the immediate-release (Phase I) to an extended-release (Phase II) formulation of diltiazem on a mg-for-mg basis or, when a similar dose was not available, to the next higher 120 mg dose. Weekly angina occurrences and nitroglycerin use, exercise testing at the end of each phase, and ambulatory electrocardiographic monitoring (AEM) during the week prior to the exercise study were evaluated.

A randomized, controlled trial comparing diltiazem, hydrochlorothiazide, and their combination in the therapy of essential hypertension.

Study Objectives: To compare the efficacy of combination therapy with sustained-release diltiazem and hydrochlorothiazide (DTZ SR-HCTZ) with that of monotherapy with DTZ SR, HCTZ, or placebo in the treatment of essential hypertension; and to determine whether the addition of a diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects.

Design: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial with a 6-week treatment phase.

Setting: Private and university-based clinics.

Amlodipine once a day in stable angina: double-blind crossover comparison with placebo.

Although calcium antagonists form a mainstay of therapy in patients with angina pectoris, the currently available agents have significant limitations. Nifedipine, diltiazem, and verapamil are all high-clearance agents with significant hepatic extraction and rapid clearance, leading to limited and short-lived bioavailability necessitating frequent daily administration. In contrast, amlodipine, a dihydropyridine calcium antagonist, has a long half-life of 35-50 h (compared with 3 to 4 h elimination half-life of diltiazem, verapamil, and nifedipine).

Metabolic consequences of treating hypertension.

Reduction of morbidity and mortality has been the aim of drug treatment for hypertension since its beginning in the 1950s. Its efficacy has been tested in many trials. An outstanding result of these trials has been their clear success in preventing stroke and stroke-related deaths and in decreasing the incidence of congestive heart failure (CHF) and renal disease.

Antihypertensive monotherapy with tablet (prompt-release) diltiazem: multicenter controlled trials.

The tablet formulation of diltiazem has been available for the treatment of angina pectoris but has not been comprehensively evaluated in hypertension. This study's aim was to evaluate the efficacy, dose-response characteristics, and duration of action of tablet (prompt-release) diltiazem in mild to moderate hypertension. Three placebo-controlled trials were designed.

Efficacy of encainide in supraventricular arrhythmias.

This review summarizes the data from all the studies conducted in the United States and Europe that have evaluated the efficacy of encainide in patients with a variety of supraventricular arrhythmias. Using clinical criteria of efficacy, encainide was found to be effective or partially effective in 77% of patients evaluated by electrophysiologic means. Similar levels of efficacy were observed in patients with AV as well as AV nodal reentry arrhythmias.

Effects of encainide on the function of implanted pacemakers.

The effect of encainide on chronic pacing thresholds was evaluated in 10 patients, age 64-89, who were exposed to weekly increased encainide dosing (25 mg TID, 50 mg TID, 75 mg TID). Median pacing threshold (mujoules) increased modestly at each period compared to placebo and returned rapidly to baseline after discontinuation. (table; see text) No patient experienced a pacing-related clinical event.

Sustained-release diltiazem: duration of antihypertensive effect.

The antihypertensive activity of a sustained-release preparation of diltiazem (given each 12 hours) was assessed in 96 patients with supine diastolic blood pressure (BP) between 95 and 110 mm Hg in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial comparing optimally titrated doses of diltiazem and placebo. The aim was to assess the onset of action as well as the extent and variability of BP control of this formulation during the 12-hour interval. Diltiazem was titrated from 120 mg bid to 180 mg bid as necessary to lower BP.

Treatment of ectopic atrial arrhythmias and premature atrial complexes in adults with encainide.

Few studies of the antiarrhythmic effects of encainide have included patients with primary atrial tachycardias and premature atrial contractions (PACs). In this review, 11 patients with primary atrial tachycardia and 10 patients with symptomatic PACs were abstracted from all studies known to have been performed. These patients had been shown to be highly resistant to prior antiarrhythmic treatments.

Metabolic effects of antihypertensive therapy with a calcium antagonist.

The effect of diuretics to increase serum glucose, low-density lipoprotein cholesterol and triglycerides, as well as the adverse changes in triglycerides and high-density lipoprotein cholesterol produced by nonselective beta blockers, have been largely ignored in the treatment of hypertension. However, a number of trials have shown that reductions in serum lipids can alter cardiovascular mortality. Calcium antagonists have become major drugs in the treatment of hypertension, and some data suggest that calcium antagonists may increase serum glucose levels.

Metabolic changes with antihypertensive therapy of the salt-sensitive patient.

Recent evidence suggests that metabolic changes that occur with antihypertensive agents may influence cardiovascular risk. Diuretic therapy is particularly appropriate for the salt-sensitive hypertensive patient. However, diuretic-induced electrolyte abnormalities may lead to ventricular arrhythmias, even in patients with uncomplicated essential hypertension.

Efficacy of a new calcium antagonist PN 200-110 (isradipine) in angina pectoris.

Angina pectoris is one of the major syndromes against which to test the therapeutic effectiveness of any new calcium antagonist. An interim analysis of the efficacy and safety of a new dihydropyridine calcium antagonist (PN 200-110 [isradipine]) in patients with confirmed coronary artery disease is reported. The study was carried out in 3 centers; 50 patients of an anticipated 96 have completed the double-blind comparative phases in 3 separate studies.

Treatment of supraventricular arrhythmias with encainide.

Encainide has been used to treat 230 patients with supraventricular arrhythmias, including patients with reentry supraventricular tachycardia of the atrioventricular reentry (Wolff-Parkinson-White syndrome) and the atrioventricular nodal reentry types associated with atrial fibrillation, paroxysmal supraventricular tachycardia or both, as well as incessant supraventricular tachycardia. The available data are summarized in this review. The short- and long-term response to encainide for preventing recurrence or lessening symptoms was excellent in most cases.