Comparison of intravenous diltiazem and verapamil for the acute treatment of atrial fibrillation and atrial flutter.

STUDY OBJECTIVES: To compare the efficacy and safety of intravenous diltiazem and verapamil in controlling ventricular rate in patients with atrial fibrillation or flutter, and to evaluate the effects of these agents on left ventricular systolic function. DESIGN: Prospective, randomized, double-blind, crossover study. SETTING: University-affiliated hospital and Veterans Administration hospital. PATIENTS: Seventeen men with atrial fibrillation or flutter with a ventricular rate of 120 beats/minute or higher and a systolic blood pressure of 100 mm Hg or greater. INTERVENTIONS: Patients received up to two intravenous boluses of either diltiazem or verapamil, followed by an 8-hour continuous infusion if a therapeutic response was achieved (phase I). After a washout period, patients who responded were crossed over to receive the other drug in a similar fashion (phase II). MEASUREMENTS AND MAIN RESULTS: At the end of each infusion, the patient's ejection fraction was assessed by gated angiography. Of the 17 men initially randomized, 8 successfully completed both phases I and II. In these patients, baseline mean (+/- SD) ventricular rates before treatment with intravenous diltiazem and verapamil were 138 +/- 15 and 132 +/- 9 beats/minute, respectively (NS). At 2 minutes after the initial bolus dose, the mean ventricular rate decreased to 100 +/- 13 beats/minute in the diltiazem group compared with 114 +/- 17 beats/minute in those receiving verapamil (p < 0.05). Mean ventricular rates of 96 +/- 11 and 97 +/- 9 beats/minute were maintained during the 8-hour continuous infusion of diltiazem and verapamil, respectively (NS). On completion of the bolus dose(s) and during continuous infusions, there were no significant differences in blood pressures between the groups. Mean ejection fractions were 35.6 +/- 13.6% and 35.5 +/- 15.4% in the diltiazem and verapamil groups, respectively (NS). For the 17 patients, the mean maximum percentage decreases in blood pressure were not significantly different between groups. However, three patients developed symptomatic hypotension, all of whom were randomized to receive verapamil initially. CONCLUSION: Intravenous diltiazem and verapamil are comparable in terms of efficacy and effect on systolic function in patients with rapid atrial fibrillation and flutter. However, hypotension may limit therapy with verapamil in some patients.

Evaluation of two forms of sustained release nifedipine using 24 h ambulatory blood pressure monitoring.

Therapeutic interchange between the available forms of sustained release nifedipine (osmotic-pump and coat-core forms of nifedipine) is a matter of controversy. This study was initiated to determine whether there is a difference in clinical outcomes when there is interchange between the two forms of sustained release nifedipine when used for the treatment of hypertension. A total of 43 patients with a history of stage I hypertension who were receiving stable doses of the osmotic-pump form of nifedipine for > 3 months with controlled blood pressures (< 150/90 mm Hg) were enrolled. Patients were then switched to the same dose of the coat-core form of nifedipine and were followed for 3 months. In the 36 patients who completed the study, mean trough serum nifedipine concentrations were significantly higher with the osmotic-pump from (46.5 +/- 35.0 ng/mL) of nifedipine compared with the coat-core form (27.2 +/- 20.4 ng/mL) (P < .05). However, blood pressure control as determined by the indices of 24 h ambulatory blood pressure monitoring, trough blood pressures and load blood pressures were similar between the osmotic-pump and coat-core forms of nifedipine. The coat-core form of nifedipine was discontinued in four patients for possible side effects. In this group of patients with mild hypertension, there were no clinically relevant differences in blood pressure control between the two forms of nifedipine. Some patients on the coat-core form of nifedipine may need to discontinue therapy due to intolerable side effects.

Economic impact of digoxin toxicity.

The costs of digoxin toxicity to the US healthcare system have not been previously reported. Therefore, the 1994 database of US University Health-System Consortium (UHC) was searched for cases of digoxin toxicity using the International Classification of Diseases (9th edition) [ICD-9] codes. In addition, the medical records of 17 patients admitted to the University of Illinois Hospital from September 1994 to July 1995 with a diagnosis of digoxin toxicity were also reviewed. Of the 17 patients, 14 were admitted with a primary diagnosis of digoxin toxicity. Causes of digoxin toxicity were worsening renal function (6 patients), excessive dosage prescribed (4 patients), excessive dosage self-administered (2 patients), multiple prescriptions (2 patients), accidental ingestion (1 patient), drug-drug interaction (1 patient) and unknown (1 patient). Digoxin toxicity could have been prevented in 9 (53%) of the 17 patients. The mean length of stay in the hospital as a result of digoxin toxicity was 3.3 +/- 1.2 days. The mean laboratory cost associated with digoxin toxicity was $US275.54 +/- $US106.57 and the mean hospital bed cost was $US3781.92 +/- $US2572.22. The mean overall cost associated with digoxin toxicity was $US4087.05 +/- $US2659.76. There was a significant correlation between the total cost associated with digoxin toxicity and the serum digoxin concentration on admission (r = 0.73, p < 0.01). From the UHC database, a total of 836 cases of digoxin toxicity in 56 hospitals were identified. This represented the occurrence of digoxin toxicity in 0.07% of all patients admitted to these US academic hospitals. Digoxin toxicity results in considerable costs to the healthcare system. Most cases can be considered readily preventable with proper patient counselling and education.

Clinical characteristics and management of acute stroke in patients with atrial fibrillation admitted to US university hospitals.

UNLABELLED: The optimal evaluation and management of patients with atrial fibrillation who suffer an acute ischemic stroke remains controversial. METHODS: Medical records of 171 consecutive patients with atrial fibrillation and acute stroke at six U.S. university hospitals were reviewed. Data collected included the use of antithrombotic therapy, brain and cardiac imaging, bleeding complications, stroke risk factors, and contraindications to anticoagulation. RESULTS: Mean age was 75.4 years. Cardiovascular risk factors associated with increased stroke risk were present in 87%; 35% had at least one contraindication to anticoagulation. Half of the patients with stroke risk factors and no contraindications to anticoagulation were not receiving any antithrombotic therapy at the time of admission. Of the 22 patients who were treated with warfarin, and had INR values on admission, 16 had levels of < 2.0; only six had INR values between 2.0 and 3.0. Transthoracic echocardiography was performed in 107 patients (63%); intracardiac thrombi were visualized in only 5%. Initial brain imaging revealed hemorrhagic transformation in nine. Heparin was used in 93 patients (54%), usually within 48 hours of stroke onset. Patients who received delayed heparin typically did not have repeat brain imaging prior to starting heparin. One patient had a delayed symptomatic cerebral hemorrhage. Of the survivors, 47% were discharged and treated with warfarin (or warfarin plus aspirin), 28% with ASA, 7% with other antithrombotic therapies, and 18% with no antithrombotic therapy. CONCLUSION: Antithrombotic therapy was underutilized and inadequately monitored in atrial fibrillation patients prior to stroke onset. After hospital admission, a wide range of diagnostic and management strategies, which often did not follow current recommendations, were employed.

Listeria monocytogenes phosphatidylinositol (PI)-specific phospholipase C has low activity on glycosyl-PI-anchored proteins.

The ability of the phosphatidylinositol-specific phospholipase C (PI-PLC) from Listeria monocytogenes to hydrolyze glycosyl phosphatidylinositol (GPI)-anchored membrane proteins was compared with the ability of the PI-PLC from Bacillus thuringiensis to hydrolyze such proteins. The L. monocytogenes enzyme produced no detectable release of acetylcholinesterase from bovine, sheep, and human erythrocytes. The cleavage of the GPI anchors of alkaline phosphatase from rat and rabbit kidney slices was less than 10% of the cleavage seen with the PI-PLC from B. thuringiensis. Activity for release of Fc gamma receptor IIIB (CD16) on human granulocytes was also low. Variations in pH and salt concentration had little effect on the release of GPI-anchored proteins. Our data show that L. monocytogenes PI-PLC has low activity on GPI-anchored proteins.