A comparison of total hospital costs for percutaneous coronary intervention patients receiving abciximab versus tirofiban.

The purpose of this study was to examine the total hospital costs associated with the receipt of abciximab versus tirofiban for percutaneous coronary intervention (PCI) patients. Hospital billing data for patients with a primary procedure of PCI was examined for the period of July 1998 to June 1999 from HCIA-Sach's Clinical Pathways Database. Data were analyzed for all patient discharges whose records indicated use of abciximab or tirofiban with a PCI. Results are reported for 3,967 patients. Multivariate analysis was used to control for a wide range of factors (GP IIb/IIIa selection, patient demographics, stent use, insurance type, health conditions, admission information, and hospital characteristics) that may influence the cost of hospitalization. A two-stage sample selection model was used to estimate total costs. The first stage of the analysis utilizes a probit regression to determine the factors associated with the likelihood of receiving abciximab versus tirofiban. The second stage of the analysis examines the factors associated with total hospital costs, while controlling for unobserved factors that may be correlated with the patient's likelihood of receiving abciximab. The mean unadjusted cost per hospitalization, including drug costs, was $10,762 (abciximab $10,813 and tirofiban $10,567). After controlling for high-risk indications and selection bias with the two-stage sample selection model, results indicate there was no significant difference in costs associated with the receipt of abciximab versus tirofiban. However, the results also indicate that the two-stage sample selection model may not be needed (lambda was not statistically significant) hence, the cost equation was reestimated using ordinary least-squares methodology (OLS). In the OLS analysis, receipt of abciximab versus tirofiban was associated with a significant reduction in costs ($470 reduction; P = 0.05). This study uses real-world data to examine the total hospital costs for PCI patients who receive abciximab versus tirofiban. Results of the two-stage sample selection model indicate there is no difference in total hospital costs (including drug costs) between abciximab- and tirofiban-treated patients. If the results of the OLS model are considered, a slight decrease in total hospital costs is observed in abciximab recipients. Cost-containment strategies that focus on component costs may not lead to intended overall cost savings.

Impact of abciximab versus eptifibatide on length of hospital stay for PCI patients.

The purpose of this study is to compare the profile of percutaneous coronary intervention (PCI) patients who receive abciximab versus eptifibatide, as well as to compare the effect of abciximab versus eptifibatide on hospital length of stay. Retrospective data were obtained from HCIA's Clinical Pathways Database on 5,446 coronary angioplasty patients who were administered either abciximab or eptifibatide. Estimation was conducted via a two-stage sample selection model. In the first stage, a probit regression was employed to determine which factors were associated with a higher probability of being administered abciximab versus eptifibatide. In the second stage, a negative binomial model was used to estimate the impact of a wide range of factors (selection of GPIIb/IIIa, patient demographics, insurance provider, health conditions, admission information, and hospital characteristics) on total hospital length of stay, as well as on postprocedural length of stay. After controlling for high-risk indications and other sources of selection bias, results indicate that receipt of abciximab was associated with a significantly shorter length of total hospital stay (0.83 fewer days; P < 0.001) than receipt of eptifibatide. Additionally, receipt of abciximab was found to be associated with a significantly shorter postprocedural hospital length of stay (0.48 fewer days; P = 0.002) compared to receipt of eptifibatide. Results of this study indicate that PCI patients who are administered abciximab versus eptifibatide have a significantly shorter length of hospital stay (both total and postprocedural). This finding is important since hospital length of stay reflects the occurrence of complications and has been found to be directly related to the resources consumed during in-patient management of patients. Cathet Cardiovasc Intervent 2001;53:296-303.

Impact of abciximab versus tirofiban on hospital length of stay for PCI patients.

The purpose of this retrospective study was to examine in a naturalistic setting the effect of abciximab versus tirofiban on hospital length of stay for patients undergoing percutaneous coronary intervention (PCI). Retrospective data were obtained from HCIASach's Clinical Pathways Database on 5,560 PCI patients who were administered either abciximab or tirofiban. Multivariate analysis was used to control for a wide range of factors (GPIIb/IIIa selection, patient demographics, insurance provider, health conditions, admission information, and hospital characteristics) that may influence hospital length of stay. Estimation was conducted via a two-stage sample selection model. After controlling for high-risk indications and sources of selection bias, results indicate that receipt of abciximab was associated with significantly shorter lengths of hospital stays compared to tirofiban (1.01 fewer days; p < 0.001). In a subgroup analysis of patients having an acute myocardial infarction (AMI; n = 2,593), receipt of abciximab was also found to be associated with significantly shorter hospital stays compared to tirofiban (0.60 fewer days; p < 0.001). Results of this study indicate that patients who are administered abciximab versus tirofiban have significantly shorter hospital stays. This reduction in length of stay may imply potential cost offsets for PCI patients who receive abciximab.

Association between abciximab and length of stay in intensive care for patients undergoing percutaneous coronary intervention. A 2-stage econometric model in a naturalistic setting.

OBJECTIVE: To examine the effect of abciximab treatment on intensive care length of stay for patients undergoing percutaneous coronary intervention (PCI). DESIGN AND SETTING: A retrospective study conducted in a naturalistic setting. METHODS: A 2-stage econometric model was used to control for the influence of possible selection bias across categories of patients and for both observable and unobservable factors correlated with each patient's treatment selection and length of stay in intensive care. Multivariate analysis was applied to control for a wide range of factors (patient demographics, insurance provider, health conditions, admission and discharge information, and hospital characteristics) that may influence intensive care length of stay. Retrospective data were obtained from HCIA's Clinical Pathways Database. PARTICIPANTS: Patients (n = 13,364) who were hospitalised in any of 87 hospitals across the US over the period from October 1, 1995 to December 1, 1996. RESULTS: After controlling for high-risk indications and selection bias, results indicated that administration of abciximab was associated with a significantly shorter length of stay in intensive care compared with not administering a GPIIb/IIIa inhibitor (0.45 fewer days; p < or = 0.0001). In a subgroup analysis of patients having an acute myocardial infarction (n = 4793), administration of abciximab was also associated with a significantly shorter intensive care stay (0.27 fewer days; p < 0.0001). CONCLUSION: Results of this study indicate that the administration of abciximab is associated with a reduction in the length of stay in intensive care. This reduction implies potential cost offsets for patients undergoing PCI who receive abciximab.

Caucasian versus African-American differences in orosomucoid: potential implications for therapy.

We conducted a prospective, nonrandomized study in healthy volunteers to determine if racial differences exist in orosomucoid (ORM) and its variants, and to examine quinidine and lidocaine binding to the protein. Total ORM serum concentrations were measured by Laurell-Rocket immunoelectrophoresis. Allele types were determined by isoelectric focusing and immunoblotting. Total and unbound quinidine and lidocaine concentrations were measured with standard fluorescence polarization immunoassays after ultrafiltration. The frequency of the common ORM alleles was similar between 38 Caucasians and 67 African-Americans. Mean total ORM concentration was significantly lower in Caucasians (57.3 +/- 25.4 vs 73.2 +/- 33.9 mg/dl, p=0.01). However, more Caucasians took oral contraceptives, which may have decreased ORM concentrations. Quinidine unbound fraction (UF) was related to ORM phenotype. The highest UF was found with ORM 1-S (p=0.009). There were no significant relationships between ORM phenotype and lidocaine UF. Overall, African-Americans had higher ORM concentrations than Caucasians. Quinidine binding showed significant relationships to specific ORM variants.

Altered protein binding of quinidine in patients with atrial fibrillation and flutter.

STUDY OBJECTIVES: To determine if alpha1-acid glycoprotein (AAG) concentrations are altered in patients with atrial fibrillation and flutter (AFF), and to establish if fluctuations in AAG change the free fraction of quinidine. DESIGN: Prospective, controlled, nonrandomized. SETTING: Tertiary care medical center and outpatient clinics. PATIENTS: Thirty patients with AFF and 16 matched controls. INTERVENTIONS: Serial blood samples were collected from patients with AFF at baseline and for 28 days after cardioversion. The control group received no treatment and a single blood sample was obtained. MEASUREMENTS AND MAIN RESULTS: Concentrations of AAG were measured by Laurell-Rocket immunoelectrophoresis. Quinidine concentrations were determined by fluorescence polarization immunoassay using the Abbott TDx system. Baseline AAG concentrations in patients with AFF (122 +/- 55 mg/dl) were significantly increased compared with the control group (62 +/- 28 mg/dl, p<0.0005). Concentrations of AAG remained elevated after conversion to sinus rhythm and did not significantly change over the study period, regardless of method of cardioversion (p>0.2). In patients with AFF, the free fraction of quinidine at the highest AAG concentration was 8.5 +/- 2.3%. This was significantly reduced compared with the value in the control group (12.5 +/- 3.0%, p<0.05) as well as that in patients with AFF at the lowest AAG concentration (11.0 +/- 2.5%, p<0.05). Overall at the highest AAG concentration, patients with AFF had a relative reduction in the quinidine free fraction by 32% compared with controls. Regression analysis showed an indirect relationship between serum AAG concentration and the unbound fraction of quinidine (r=0.56) CONCLUSIONS: Concentrations of AAG are increased in patients with AFF and remain elevated for at least 28 days after cardioversion. Elevated AAG concentrations significantly reduce the free fraction of quinidine.

Role of microtubules in contractile dysfunction of hypertrophied cardiocytes.

Cardiac hypertrophy in response to systolic pressure overloading frequently results in contractile dysfunction, the cause for which has been unknown. Since, in contrast, the same degree and duration of hypertrophy in response to systolic volume overloading does not result in contractile dysfunction, we postulated that the contractile dysfunction of pressure hypertrophied myocardium might result from a direct effect of stress as opposed to strain loading on an intracellular structure of the hypertrophied cardiocyte. The specific hypothesis tested here is that the microtubule component of the cytoskeleton is such an intracellular structure, which, forming in excess, impedes sarcomere motion. The feline right ventricle was either pressure overloaded by pulmonary artery banding or volume overloaded by atrial septotomy. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. We show here that stress loading increases the microtubule component of the cardiac muscle cell cytoskeleton; this apparently is responsible for the entirety of the cellular contractile dysfunction seen in our model of pressure-hypertrophied myocardium. No such effects were seen in right ventricular cardiocytes from normal or volume-overloaded cats or in left ventricular cardiocytes from any group of cats. Importantly, the linked microtubule and contractile abnormalities are persistent and thus may be found to have significance for the deterioration of initially compensatory cardiac hypertrophy into the congestive heart failure state.

Sotalol: a breakthrough antiarrhythmic?

OBJECTIVE: To review the pharmacology, pharmacokinetic, dosing, adverse effects, and therapeutic uses of sotalol. DATA IDENTIFICATION: Articles were identified with an English-language literature computer search via Knowledge Finder, using the term sotalol, and with an extensive search of bibliographies of identified articles. STUDY SELECTION: Relevant or representative animal studies, human trials, and case reports were selected for evaluation. DATA EXTRACTION: The literature was assessed for quality, methodology, and outcome information. DATA SYNTHESIS: Sotalol is a racemic compound with Class II (beta-blocking properties) and Class III (prolonged action potential) antiarrhythmic activity. It has been suggested that the plasma concentration associated with QTc prolongation (a measure of the Class III action) is much greater than that associated with beta-blockade. Therefore, sotalol is categorized as a Class III antiarrhythmic agent. The 1-isomer is responsible for the beta-blocking activity, whereas both isomers have Class III properties. After oral dosing in fasting patients with normal renal function, sotalol is > 90 percent absorbed, achieves peak serum concentrations in 2-4 h, is excreted unchanged 80-90 percent in the urine, has a volume of distribution of 1-2 L/kg, and has an elimination half-life of about 12 h. Sotalol is effective in patients with life-threatening ventricular arrhythmias that have been refractory to other conventional antiarrhythmic drugs. In general, sotalol appears to be well tolerated, with many of its adverse effects caused by beta-blocking activity. As with other antiarrhythmic agents, the possibility of proarrhythmia (frequently torsade de pointes) exists. CONCLUSIONS: Racemic sotalol is an effective Class III antiarrhythmic agent approved by the Food and Drug Administration for the treatment of documented life-threatening ventricular arrhythmias. Investigations continue with racemic sotalol in the management of supraventricular arrhythmias. Trials with the d-isomer are also ongoing.

Rapid expression of the Na(+)-Ca2+ exchanger in response to cardiac pressure overload.

This report identifies a rapid increase in the expression of cardiac Na(+)-Ca2+ exchanger mRNA in response to an acute pressure overload. This enhanced exchanger expression appeared within 1 h after the onset of right ventricular pressure overload in the cat and was sustained during cardiac overloading for at least 4 h. Maintenance of this right ventricular pressure overload for 48 h evoked an increase in the production of exchanger protein. Because of our previous finding that load imposition on the heart initiates cell growth and our hypothesis that this is in response to the enhanced entry of cellular cations, we then examined the effect of Na+ influx into cultured adult cardiac myocytes, or cardiocytes, in terms of early anabolic responses. Pressure overload of the heart and cardiocyte Na+ influx were found to produce a common, rapid result in terms of both enhanced Na(+)-Ca2+ exchanger expression and accelerated synthesis of general and contractile proteins, the hallmarks of cardiac hypertrophy.

Concomitant amiodarone and the implantable cardioverter-defibrillator: is there a place?

OBJECTIVE: To discuss the controversy surrounding concomitant therapy with amiodarone and the implantable cardioverter-defibrillator (ICD). DATA SOURCES: A MEDLINE search identified English-language literature sources, including nonhuman studies. STUDY SELECTION: Studies included those that specifically addressed the use of amiodarone plus the ICD as well as reviews of the ICD. DATA EXTRACTION: Studies were evaluated for design, type of defibrillation electrode or defibrillator, method of defibrillation, amiodarone loading and maintenance dosages, duration of amiodarone therapy, and study endpoints. DATA SYNTHESIS: Because the ICD functions by delivering energy to depolarize a mass of myocardium, concomitant use of antiarrhythmic agents that elevate the defibrillation threshold (DFT) beyond an ICD's energy capability may adversely effect patient outcome. Amiodarone has been shown to both increase and decrease the DFT. Trials examining the use of amiodarone plus the ICD have not provided strong evidence that amiodarone will decrease the number of ICD discharges or favorably affect the mortality rate. Amiodarone is also expensive and toxic. Although the cost of the ICD is relatively high, continuing improvements in battery life will decrease long-term costs. CONCLUSIONS: Controlled trials are required to substantiate the improved survival rate with the ICD and to determine the role of antiarrhythmic agents in conjunction with the device. At present, there are no data to support the combination of amiodarone and an ICD in terms of improved quality or duration of life.

Impact of food on the pharmacokinetics and electrocardiographic effects of sustained release verapamil in normal subjects.

To evaluate the impact of food on the pharmacokinetics and electrocardiographic effects of sustained release (SR) verapamil tablets, 9 healthy men each received 3 single doses of verapamil in a randomized, crossover manner: 10 mg of intravenous verapamil, 240 mg SR verapamil on an empty stomach, and 240 mg SR verapamil with a standardized meal. PR intervals and racemic verapamil serum concentrations were measured serially over 30 hours after administration. The time to peak concentration was longer (7.5 +/- 3.0 vs 4.4 +/- 2.3 hours), resulting in a lower peak verapamil serum concentration (118 +/- 43 vs 175 +/- 50 ng/ml) when SR verapamil was administered with food (p < 0.05). Food tended to decrease the bioavailability of SR verapamil (34 +/- 12 vs 49 +/- 14%), although this difference did not reach statistical significance (p = 0.065). Precipitous or exaggerated release of verapamil from the SR tablet was not observed in any subject during the fasting state. Prolongation of the PR interval paralleled these alterations in serum concentration. The maximal change in the PR interval was greater (21 +/- 8 vs 14 +/- 5%; p < 0.05) when SR verapamil was given in the fasting state. Although an exaggerated verapamil release or effect was not observed, food significantly altered the absorption and electrocardiographic effects of a single dose of SR verapamil. Manipulation of the administration condition may be helpful in achieving desired outcomes.

Evaluation and treatment of ventricular arrhythmias: an update.

An overall approach to evaluating and treating ventricular arrhythmias based on objective monitoring criteria is described. A clinically useful system classifies patients based on whether their ventricular arrhythmias are benign, potentially lethal, or lethal. Some clinicians believe that antiarrhythmic drug therapy improves survival in patients with potentially lethal arrhythmias. However, disappointing results from the Cardiac Arrhythmia Suppression Trial have led to a greater awareness of the potential adverse effects of antiarrhythmics. Various risk factors for arrhythmia-related death have been identified, such as the presence of frequent and complex ventricular ectopy, abnormal signal-averaged electrocardiography (SAECG) tracings, and poor left ventricular ejection fraction (LVEF). Antiarrhythmic drugs remain the primary mode of therapy for patients with recurrent symptomatic tachycardias. Antiarrhythmic drug efficacy has been evaluated by methods including symptom assessment, continuous ambulatory electrocardiographic monitoring (Holter monitoring), exercise testing, and invasive electrophysiologic testing. There may be an extremely wide range of effective serum concentrations for the class IA agents. Individual target concentrations of antiarrhythmic agents may be determined for individual patients and should assist the clinician in optimizing long-term antiarrhythmic drug therapy. The risk-to-benefit ratio of treatment should be weighed before antiarrhythmic drug therapy is begun, and careful, objective monitoring of drug efficacy should be performed. When pharmacologic treatment of ventricular arrhythmias is considered, treatment algorithms that incorporate LVEF measurements, Holter monitor recordings, and SAECG may aid the clinician.

Adenosine in the episodic treatment of paroxysmal supraventricular tachycardia.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of adenosine in the treatment of episodes of paroxysmal supraventricular trachycardia (PSVT) are reviewed. Adenosine is an endogenous adenine nucleoside that markedly decreases heart rate and prolongs atrioventricular (AV)-nodal conduction. Adenosine is rapidly cleared from plasma by the cellular elements of the blood and by vascular endothelial cells and subjected to enzymatic metabolism. The drug has a half-life of 0.6 to 10 seconds. In noncomparative clinical trials, adenosine terminated 85% to 100% of induced or spontaneous episodes of PSVT involving the AV node in the reentrant circuit. In patients with arrhythmias that do not involve the AV node in the reentrant circuit, adenosine produces AV block and does not restore sinus rhythm. Prospective, randomized trials comparing adenosine with verapamil in adults have not yet been performed. The adverse effects of adenosine include flushing, dyspnea, headache, cough, chest pain, sinus bradycardia, atrial fibrillation, ventricular arrhythmias, and various degrees of AV block. Because of the short half-life of adenosine, these effects are transient and well tolerated. The initial dose of adenosine in treating acute PSVT is 6 mg given by rapid i.v. bolus injection, followed in one to two minutes by up to two additional 12-mg boluses if necessary. Adenosine has been found to be effective in terminating PSVT and thus offers an alternative to verapamil. Prospective, randomized trials comparing adenosine with verapamil are needed to definitively establish adenosine's role in the therapy of PSVT.

Propafenone: a novel type Ic antiarrhythmic agent.

Propafenone is an investigational type Ic anti-arrhythmic agent that markedly slows conduction velocity in all cardiac tissues. Propafenone also possesses weak beta- and calcium-channel blocking properties. The bioavailability of propafenone is dose-dependent. Hepatic metabolism of this agent is polymorphic and appears to correlate with the ability of the liver to oxidize debrisoquin sulfate. Propafenone is effective in suppressing spontaneous ventricular ectopy; however, the drug may be less effective in patients with sustained ventricular tachycardia or ventricular fibrillation when evaluated using programmed stimulation. Propafenone is also useful in the treatment of supraventricular tachycardias including atrioventricular (AV) nodal reentrant tachycardia, AV reentrant tachycardia associated with the Wolff-Parkinson-White syndrome, and atrial fibrillation. Adverse reactions seen with propafenone affect the gastrointestinal, central nervous, and cardiovascular systems. Comparative studies with currently available type Ic agents are needed to better define propafenone's place in therapy.

Proarrhythmia: a paradoxic response to antiarrhythmic agents.

Antiarrhythmic drugs may effectively terminate and prevent symptomatic tachycardias, but they may also provoke life-threatening rhythm disturbances. The electrophysiologic mechanisms responsible for proarrhythmia can be extrapolated from the existing models of reentry and abnormal automaticity. Although all antiarrhythmic drugs may cause proarrhythmia with seemingly similar frequency, the profile of the disturbance with each class of agents appears somewhat distinct. All agents may cause an increased frequency of premature beats or new or worsened ventricular tachycardia, but the classic form of proarrhythmia due to type la agents is torsades de pointes. Recent information has provided clues to the underlying mechanism of drug-induced torsades de pointes and has provided a clinical picture of patients with this adverse effect. Types lb and lc agents only rarely precipitate torsades de pointes. The latter, however, may cause a rapid, sustained, monomorphic ventricular tachycardia in certain high-risk patients that can be resistant to resuscitation efforts. Amiodarone may cause a broad variety of arrhythmias that are complicated by their extended duration and difficulty in distinguishing proarrhythmia from simple inefficacy. Proarrhythmia is a relatively common, paradoxic side effect that necessitates the clinician to make careful risk-benefit decisions in choosing antiarrhythmic drug therapy.