This single-blind, placebo-controlled study evaluated long-term therapy with cibenzoline in 19 patients with chronic ventricular arrhythmias. Antiarrhythmic efficacy, defined as greater than or equal to 75% reduction in single premature ventricular complexes (PVCs), greater than or equal to 90% reduction in paired PVCs, and total abolition of ventricular tachycardia (VT), was established after dose titration in 14 of 19 (74%) patients. Mean frequency of single PVCs was reduced by 65%, mean paired PVC frequency was reduced by 68%, and mean VT event frequency was reduced by 82%. Antiarrhythmic efficacy was maintained during long-term therapy in five of the 14 (36%) short-term responders. Of the nine patients who discontinued cibenzoline during long-term follow-up, five had a loss of arrhythmia control, three failed to redevelop arrhythmias during placebo reintroduction, and one developed an adverse reaction. Three patients (16%) experienced a proarrhythmic effect. Echocardiographic evaluation did not reveal any deleterious effect of cibenzoline on left ventricular function in the group as a whole. In six patients with preexisting left ventricular dysfunction, left ventricular ejection fraction and fractional shortening improved significantly (P less than .05) during cibenzoline therapy. Adverse effects occurred in seven patients (37%) but necessitated drug discontinuation in only one patient (5%). Cibenzoline provides effective short-term therapy for patients with chronic ventricular arrhythmias. Long-term therapy must be assessed periodically to ensure continued efficacy. Drug-related adverse effects occur infrequently. Cibenzoline can be used safely in patients with compensated left ventricular dysfunction.

Adult↗

PubMedDate not supplied

Outcomes and costs of positron emission tomography: comparison of intravenous adenosine and intravenous dipyridamole.

The objective of this study was to compare the cost of intravenous adenosine and intravenous dipyridamole in positron emission tomography (PET) in patients with coronary artery disease. A retrospective, open-label, case-control, cost-effectiveness analysis was performed in the out-patient nuclear medicine department of a university hospital. Thirty-six patients underwent dipyridamole PET, and 72 matched patients underwent adenosine PET. A cost-effectiveness analysis was conducted using a direct cost accounting approach to estimate institutional costs. Key costs evaluated included acquisition cost, administration cost, monitoring cost, cost of management of side effects, and cost of follow-up care. The total cost of adenosine PET and dipyridamole PET was divided by their respective predictive accuracies to provide a total cost adjusted for efficacy. Adenosine increased heart rate and lowered systolic blood pressure to a significantly greater extent than dipyridamole. The number of patients experiencing adverse drug reactions was significantly greater for adenosine (82%) than for dipyridamole (67%), but the frequency of prolonged (> 5 minutes) and late-onset side effects was significantly greater for dipyridamole than for adenosine. The frequency of side effects requiring medical intervention was also significantly greater for dipyridamole (53%) than for adenosine (6%). Although adenosine had a significantly greater acquisition cost than dipyridamole, costs of monitoring, management of side effects, and follow-up care were significantly less for adenosine than for dipyridamole. As a result, the total cost of using dipyridamole is significantly greater ($928.00 per patient) than the total cost of using adenosine ($672.00 per patient). Based on these results, adenosine may be the drug of choice for pharmacologic vasodilation for PET.

Adenosine↗

PubMedDate not supplied

The effects of tocainide on audiological and electrophysiological responses in humans.

This study reports on the systematic audiological evaluation of 18 cardiac patients receiving tocainide, an orally administered cardiac antiarrhythmic agent. The results of an audiological site of lesion test battery were compared with auditory brain stem response (ABR) measures. Of 35 ears tested, 17 (48%) presented ABR findings consistent with retrocochlear pathology. Audiological signs of retrocochlear pathology occurred less frequently and often in patients in whom ABR results suggested normal hearing or cochlear hearing loss. These data demonstrate that an extraneous agent, in this case tocainide, can affect ABR transmission times and that it is important to recognize such possible effects in order to interpret ABR data appropriately.

Audiometry, Evoked Response↗

PubMedDate not supplied

Comparative bioequivalence and efficacy of two sustained-release procainamide formulations in patients with cardiac arrhythmias.

This investigation evaluated the bioequivalence and efficacy of two sustained-release procainamide products. Ten patients with cardiac arrhythmias were randomized to product A (Procan-SR) or product B (Pronestyl-SR). After nine doses of study medication, plasma procainamide and N-acetylprocainamide concentrations were obtained to determine the area under the concentration versus time curve at steady state (AUCSS), mean plasma concentration (CSSav), the observed peak plasma concentration (CSSmax), the observed trough plasma concentration (CSSmin), and the apparent time to achieve CSSmax (tmax). The products were compared on a milligram-equivalent (adjusted) basis. Following completion of blood sampling, patients were crossed-over to the alternate product. There was no washout between treatments. After nine doses of the alternate test medications, blood sampling was repeated. Differences in AUCSS, CSSav, CSSmax, tmax, and intradose peak/trough ratios were not statistically significant. Within-group variability in AUCSS, CSSav CSSmax, and tmax was greater with product B, but this trend did not reach statistical significance. Antiarrhythmic efficacy was not significantly different between the two treatments. Although the greater bioequivalence, lesser variability, and the greater number of tablet dosage sizes would favor product A, patients stabilized on a particular brand of sustained-release procainamide should not be switched to another product without careful monitoring. One patient in this study developed nonsustained ventricular tachycardia with low procainamide plasma concentrations after being switched from product A to product B.

Acecainide↗

PubMedDate not supplied

A comparison of sublingual nifedipine versus nitroglycerin in the treatment of acute angina pectoris.

The administration of nifedipine by the sublingual rather than the oral route has been suggested to provide a more rapid onset of effect. We compared the safety and efficacy of sl nifedipine to sl nitroglycerin in patients who developed anginal chest pain during diagnostic exercise stress testing. Consecutive patients undergoing diagnostic Bruce treadmill exercise who had not had a recent myocardial infarction or undergone coronary bypass graft surgery and who were not taking nitrates, beta-blockers, digoxin, or calcium antagonists were eligible. Seventy-eight patients meeting the inclusion/exclusion criteria consented to participate. Of these 78, 13 developed chest pain necessitating exercise cessation and were randomized to either nitroglycerin or nifedipine. Nitroglycerin was initially given to seven patients and nifedipine to six patients. Complete pain relief was observed in five of seven (71 percent) nitroglycerin patients at two minutes postdose. At four minutes postdose, the remaining two nitroglycerin patients were essentially pain-free. At two minutes postdose, no patient receiving nifedipine had complete pain resolution, and only one patient (17 percent) had partial (greater than 50 percent) pain relief. At four minutes postdose, four of the nifedipine patients were crossed over to nitroglycerin. At two minutes after the nitroglycerin dose, all four patients had total pain relief. The remaining two nifedipine patients had partial pain relief and were not crossed over to nitroglycerin. Subjective side effects and changes in heart rate and blood pressure were not significantly different between nitroglycerin and nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMedDate not supplied

Gender and racial bias in clinical pharmacology trials.

Explore the source record for details and available documents.

Clinical Trials as Topic↗

PubMedDate not supplied

Cost-minimization analysis of initial antihypertensive therapy in patients with mild-to-moderate essential diastolic hypertension.

In addition to efficacy and safety, the cost of therapy has become an increasingly important factor to consider when selecting drugs to treat patients with mild-to-moderate hypertension. However, acquisition prices alone do not determine the total cost of therapy. To better assess total costs, we conducted a systematic, retrospective, cost-minimization analysis of drugs used to treat 673 patients with newly diagnosed, mild-to-moderate (> 95 to < 110 mmHg) diastolic hypertension between the years 1985 and 1992. Patients included in the study had started antihypertensive monotherapy, and a minimum of one dose titration was required before adding another antihypertensive agent to the regimen. A patient had to have a diastolic blood pressure of < or = 90 mmHg while undergoing therapy to be included in the analysis. Drug classes included diuretics, beta-adrenergic blockers, centrally acting alpha 2-agonists, alpha 1-adrenergic blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Costs, adjusted to 1992 price levels, were analyzed for 32 individual agents for each of the following five cost variables: initial drug acquisition, supplemental drug acquisition, laboratory monitoring, clinic visits, and treatment of side effects. Mean total costs per patient for all five variables by drug class were $895 for beta-blockers, $1043 for diuretics, $1165 for centrally acting alpha 2-agonists, $1243 for ACE inhibitors, $1288 for alpha 1-blockers, and $1425 for calcium channel blockers. However, costs within each class varied considerably. Acquisition cost was often a poor predictor of the total cost of treatment. Therefore, acquisition cost must be considered in conjunction with a number of outcome variables to assess the true cost of antihypertensive therapy.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Conversion from sustained-release to immediate-release calcium entry blockers: outcome in patients with mild-to-moderate hypertension.

We evaluated 110 patients with mild-to-moderate hypertension (diastolic blood pressure 95 to 110 mmHg) whose blood pressure was initially controlled on monotherapy with once-daily sustained-release calcium entry blockers; these patients were then switched to their respective immediate-release formulations TID. The study group consisted of 35 patients on diltiazem controlled delivery (CD) switched to immediate-release diltiazem, 41 patients on nifedipine gastrointestinal therapeutic system (GITS) switched to immediate-release nifedipine, and 34 patients on verapamil sustained-release (SR) switched to immediate-release verapamil. Outcome evaluation included a pair-wise comparison of the following during treatment with both formulations: blood pressure control, need for additional hypertensive agents, side effects, compliance, and cost of therapy. Blood pressure was controlled in 94% of patients switched from diltiazem CD to immediate-release diltiazem; 6% of patients required additional antihypertensive agents. Side effects and compliance were not significantly different between groups. Blood pressure was controlled in 78% of patients switched from nifedipine GITS to immediate-release nifedipine; 22% of patients required additional antihypertensive agents. Side effects, compliance, and cost of therapy were significantly different between groups. Side effects increased from 32% on nifedipine GITS to 58% on immediate-release nifedipine; and compliance decreased from 93% on nifedipine GITS to 76% on immediate-release nifedipine (P < 0.05). Blood pressure was controlled in 91% of patients switched from verapamil SR to verapamil immediate release; 9% of patients required additional antihypertensive agents. Side effects and compliance were not significantly different between groups, but immediate-release verapamil was significantly less expensive than verapamil SR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Safety of different dosages of intravenous adenosine used in conjunction with diagnostic myocardial imaging techniques.

STUDY OBJECTIVE: To determine the safety of three different dosage regimens of intravenous adenosine. DESIGN: Open-label, observational safety evaluation. SETTING: University hospital-based department of nuclear medicine. PATIENTS: Cohort of 854 patients referred for myocardial perfusion imaging to evaluate their coronary artery disease and who were judged unable to perform physical exercise. INTERVENTIONS: Subjects underwent myocardial perfusion imaging in conjunction with one of three intravenous dosage regimens: 1 = fixed dosage 140 micrograms/kg/minute for 6 minutes; 2 = dosage titration to a maximum of 140 micrograms/kg/minute; and 3 = dosage titration to a maximum of 200 micrograms/kg/minute. In regimens 2 and 3, maximum tolerated dosages were continued for a minimum of 3 minutes prior to radioisotope injection. MEASUREMENTS AND MAIN RESULTS: Adenosine-induced hemodynamic, electrocardiographic, and biochemical changes were measured. Adverse effects of the different adenosine dosages were compared. Noncardiac side effects such as flushing, dyspnea, neck tightness, and lightheadedness occurred at a significantly higher rate during regimens 2 and 3 than regimen 1. Chest pain and first- and second-degree atrioventricular block were also more frequent during regimens 2 and 3. However, the frequency of other side effects such as complete heart block, hypotension, and ST segment depression did not differ among the regimens. High-dose adenosine was associated with a significant increase in serum uric acid, a significant decrease in blood glucose, and a significant increase in serum triglyceride levels. Mean changes in hemodynamics and electrocardiographic intervals were also not different among the groups except for a greater increase in PR interval in regimens 2 and 3 than regimen 1. Discontinuation of adenosine was infrequent (< 1%) and did not differ among the regimens. CONCLUSIONS: Adenosine-assisted myocardial perfusion imaging procedures are relatively safe for evaluating coronary artery disease. Despite 82% of patients reporting at least one side effect, only 10 (< 1%) had to discontinue adenosine. No patient suffered any residual sequelae from the adverse effects. The fixed-dose regimen is associated with fewer subjective side effects and is better tolerated than titration regimens. Appropriate safety precautions should nonetheless be taken during adenosine infusions.

Adenosine↗

PubMedDate not supplied

The comparative safety and diagnostic accuracy of adenosine myocardial perfusion imaging in women versus men.

STUDY OBJECTIVE: To determine if the diagnostic accuracy and safety of intravenous adenosine myocardial perfusion imaging is significantly different in men compared with women. DESIGN: Prospective, comparative, open-label clinical trial. SETTING: Nuclear medicine laboratory in a university-affiliated hospital. PATIENTS: Consecutive patients who were referred for evaluation of known or suspected coronary artery disease. Patients were judged not to be able to exercise adequately. INTERVENTIONS: Coronary angiography was conducted within 6 weeks of an adenosine thallium-201 myocardial perfusion imaging study. MEASUREMENTS AND MAIN RESULTS: Diagnostic accuracy is shown in the table. [table: see text] Overall, side effects from adenosine were not different between men and women. The frequencies of ST depression and chest pain were significantly greater in women than men, although their etiologies are unknown. The frequency of severe side effects such as heart block and hypotension was not different between men and women. CONCLUSIONS: The diagnostic accuracy and safety of adenosine thallium-201 myocardial perfusion imaging are generally similar in women and men.

Adenosine↗

PubMedDate not supplied

Double-blind, randomized, placebo-controlled evaluation of atropine to prevent vasovagal reaction during removal of femoral arterial sheaths.

STUDY OBJECTIVE: To evaluate the efficacy and safety of atropine in preventing vasovagal reactions (VVRs) during removal of femoral arterial sheaths after diagnostic left heart catheterization. DESIGN: Prospective, double-blind, randomized, placebo-controlled study. SETTING: University-affiliated, 450-bed teaching hospital. PATIENTS: One hundred sixty-five patients undergoing left heart catheterization. INTERVENTIONS: Eighty-eight patients were assigned to receive atropine 0.5 mg intravenously and 77 received placebo 5 minutes before sheath removal. MEASUREMENTS AND MAIN RESULTS: The frequency of VVRs was significantly reduced in the atropine group compared with the placebo group, 2.3% and 10.4%, respectively (overall relative risk in the atropine group 0.22, 95% CI 0.12-0.41, p=0.03). Significant decreases in systolic (35.2 +/- 5.8 mm Hg, p<0.001) and diastolic blood pressures (12.6 +/- 12.6 mm Hg, p=0.002) occurred in the 10 patients with VVRs compared with those without VVR. No cardiac arrhythmias occurred after atropine administration. Dry mouth was the only side effect reported with atropine (8/88, 9%). CONCLUSION: Atropine significantly reduced the frequency of VVRs associated with removal of femoral arterial sheaths after diagnostic left heart catheterization. The drug should be studied in a larger series of patients to assess its ability to decrease the morbidity and costs associated with VVR.

Atropine↗

PubMedDate not supplied

Effect of oral H2-receptor antagonists on left ventricular systolic function and exercise capacity in patients with chronic stable heart failure.

STUDY OBJECTIVE: To evaluate the effect of cimetidine, famotidine, ranitidine, and placebo on left ventricular systolic function, aerobic metabolic performance, and exercise capacity in patients with chronic, stable heart failure. DESIGN: Double-blind, randomized, placebo-controlled, four-way crossover study. SETTING: Outpatient, university-affiliated cardiology clinic. PATIENTS: Twelve men with stable New York Heart Association class II or III heart failure secondary to ischemic heart disease or hypertension. INTERVENTIONS: Patients received in random sequence cimetidine 400 mg twice/day, famotidine 40 mg/day, ranitidine 150 mg twice/day, and placebo. Each treatment was administered for 7 days, and the periods were separated by a 1-week washout. MEASUREMENTS AND MAIN RESULTS: Before and after each treatment, patients underwent a bicycle stress echocardiogram with aerobic metabolic assessment. Left ventricular function was evaluated by calculating ejection phase indexes from Doppler echocardiographic measurements. All 12 patients successfully completed the study. No patient reported any adverse effect attributed to study drugs. None of the treatments was associated with significant changes in any measure of left ventricular systolic function, aerobic metabolic performance, or exercise capacity, nor were placebo-subtracted differences for the agents significantly different for any of the three measures. CONCLUSION: The three H2-receptor antagonists administered for 7 days at clinical dosages have no significant effect on left ventricular systolic function, aerobic metabolic performance, or exercise capacity in men with class II or III stable heart failure.

Administration, Oral↗