Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association.

Heart failure is a common, costly, and debilitating syndrome that is associated with a highly complex drug regimen, a large number of comorbidities, and a large and often disparate number of healthcare providers. All of these factors conspire to increase the risk of heart failure exacerbation by direct myocardial toxicity, drug-drug interactions, or both. This scientific statement is designed to serve as a comprehensive and accessible source of drugs that may cause or exacerbate heart failure to assist healthcare providers in improving the quality of care for these patients.

Key articles and guidelines in the management of hypertension: 2008 update.

Hypertension remains a major risk factor for cardiovascular disease. The optimal choice of pharmacologic and nonpharmacologic treatment regimens is based on a plethora of published literature. This compilation is the initial update to the Key Articles and Guidelines in the Management of Hypertension authored by members of the Cardiology Practice and Research Network of the American College of Clinical Pharmacy, which appeared in Pharmacotherapy in 2004. We present synopses of clinical trials, meta-analyses, clinical practice guidelines, and other pertinent literature published between May 2003 and June 2007.

Prevalence of anemia in clinic patients with heart failure and cost analysis of epoetin treatment.

STUDY OBJECTIVES: To determine the prevalence of anemia in an outpatient heart failure clinic, describe the type of anemia in patients treated there, and evaluate the potential costs associated with epoetin therapy in this cohort. DESIGN: Single-center, retrospective cohort analysis (part 1) and a literature-based economic decision analysis (part 2). DATA SOURCE: Medical records from a multidisciplinary, outpatient, heart failure clinic, and published hospitalization and drug-use data. PATIENTS: We evaluated 170 adults with chronic heart failure who were enrolled in the clinic and for whom at least one complete blood count was recorded between January 1, 2003, and April 15, 2006. MEASUREMENTS AND MAIN RESULTS: In part 1, demographic and clinical data were extracted from electronic medical records. The overall prevalence of anemia was 47.6% or 47.1%, as based on World Health Organization or National Kidney Foundation definitions, respectively. Normocytic anemia was characterized in 75.0% of patients. In part 2, heart failure hospitalization rates and costs, drug acquisition, and drug administration were estimated by using the published literature. In a hypothetical cohort of 100 patients with heart failure and comorbid anemia, the costs associated with outpatient epoetin and intravenous iron therapy exceeded savings in hospitalization costs by $83,070. Results of 1-way sensitivity analyses generally confirmed robustness of the model. CONCLUSION: Anemia is a common comorbidity in patients with chronic heart failure treated in the outpatient clinic. Although the current evidence is insufficient to support the use of epoetin in this population, initial findings indicate that epoetin and intravenous iron therapy may be associated with positive clinical outcomes. From a pharmacoeconomic standpoint, however, a reduction in the cost of heart failure-related hospitalization does not offset the cost of epoetin and intravenous iron therapy.

Efficacy and safety of a furosemide continuous infusion following cardiac surgery.

OBJECTIVE: To review the literature regarding the efficacy and safety of continuous intravenous infusion of loop diuretics following cardiac surgery. DATA SOURCES: Articles were identified through a MEDLINE search (1966-March 2006) using the key words furosemide, bumetanide, torsemide, ethacrynic acid, loop diuretics, continuous infusions, intravenous infusions, surgery, cardiac surgery, cardiovascular surgery, and thoracic surgery. Search results were limited to studies in human subjects published in English. Additional references were identified through review of the bibliographies of the articles cited. STUDY SELECTION AND DATA EXTRACTION: All clinical trials and observational reports identified that evaluated or described the efficacy and/or safety of a continuous infusion of a loop diuretic in adult or pediatric patients who had undergone cardiac surgery were included in this review. DATA SYNTHESIS: Loop diuretics are often used to promote diuresis following cardiac surgery. Studies in patients who have undergone cardiac surgery have demonstrated that a more consistent and sustained diuresis is produced by a continuous infusion of furosemide compared with intermittent bolus doses of furosemide. However, there does not appear to be a significant difference in total urine output or change in serum electrolyte levels when furosemide is administered as a continuous infusion compared with intermittent bolus doses. CONCLUSIONS: A continuous infusion of furosemide is an effective and safe method of diuresis in patients undergoing cardiac surgery.

Adherence to the NASPE guideline for amiodarone monitoring at a medical university.

OBJECTIVE: Amiodarone is an effective antiarrhythmic, but the clinical usefulness of this agent is complicated by its extensive side-effect profile, which necessitates careful patient selection and frequent monitoring. The purpose of this study was to quantify adherence to published recommendations for baseline monitoring when initiating inpatient amiodarone therapy at a university teaching hospital and determine whether appropriate serial monitoring of chronic amiodarone therapy (>or= 6 months) is occurring in the outpatient setting. METHODS: A retrospective review of electronic medical records was conducted for inpatients at the Medical University of South Carolina (MUSC) who received amiodarone between November 1, 2003, and March 31, 2004, and for a subset of outpatients who had received amiodarone therapy for at least 6 months. Their medical records were reviewed for demographic data; reason for, date of initiation of, and duration of amiodarone therapy; and the occurrence of laboratory and diagnostic tests. The amiodarone guideline from the North American Society of Pacing and Electrophysiology (NASPE) was used as the measure of appropriate monitoring for baseline and follow-up chest x-rays (CXRs), liver function tests (LFTs), thyroid function tests (TFTs), and pulmonary function tests (PFTs). RESULTS: Over the 5-month period from November 1, 2003, through March 31, 2004, 277 adult patients received oral amiodarone as inpatients at MUSC. Of these, 45 patients (16%) were initiated on chronic amiodarone therapy during their hospital admission. Baseline assessments of CXRs, LFTs, and TFTs occurred in 82% to 87% of these patients. Baseline assessment of PFTs occurred in 24% of patients, and 55% of these assessments included a diffusion capacity (DLCO). Overall, only 5 (11%) of the 45 patients initiated on amiodarone received all recommended monitoring tests. Twenty patients with available outpatient records in the MUSC system were identified as receiving chronic amiodarone therapy. Baseline assessments of LFTs, TFTs, and CXRs occurred in approximately 75% to 95% of these patients; baseline assessment of PFTs occurred in

Biliary sludge and hyperbilirubinemia associated with ceftriaxone in an adult: case report and review of the literature.

Ceftriaxone is a commonly used third-generation cephalosporin that has antimicrobial activity against many gram-positive and gram-negative organisms. Generally, ceftriaxone is a safe antibiotic; however, symptomatic biliary sludge has been reported in rare instances, most of which have involved children. It is uncommon for ceftriaxone to cause increases in laboratory indexes, such as bilirubin levels. We describe the case of a 53-year-old man who was treated with intravenous ceftriaxone 2 g every 12 hours. After 7 days of therapy, the patient's liver function test results, including total, direct, and indirect bilirubin levels, increased significantly from baseline, and the patient became jaundiced. A right upper quadrant ultrasound examination revealed biliary sludge and cholelithiasis without sonographic evidence of cholecystitis. Ceftriaxone was thought to be the responsible agent, and it was discontinued. The patient's jaundice subsided, and his liver function test results improved, returning to baseline within 14 days. Clinicians need to be aware of the association of ceftriaxone and biliary pseudolithiasis and hyperbilirubinemia, and monitor accordingly.

Experience with an adult alcohol withdrawal syndrome practice guideline in internal medicine patients.

STUDY OBJECTIVE: To standardize treatment of alcohol withdrawal syndrome (AWS) in internal medicine patients using an adult AWS practice guideline with a symptom-triggered management approach. DESIGN: Prospective interventional (pilot group) and retrospective (control group). SETTING: University teaching hospital. PATIENTS: Thirty-two internal medicine patients identified as being at risk for AWS and treated according to the AWS practice guideline who were compared with 49 internal medicine patients managed with nonstandardized approaches. INTERVENTION: Patients in the pilot group were assessed using the AWS type indicator. They received lorazepam, clonidine, or haloperidol, based on AWS type indicator assessment and adult AWS practice guideline criteria. MEASUREMENTS AND MAIN RESULTS: Data collected and analyzed were drugs administered to control AWS symptoms, use of sitters and physical restraints, length of hospital stay, and discharge from hospital receiving tapered drug therapy. Pilot patients received 46.6% less benzodiazepine (p=0.001), 20% more clonidine (p=0.01), and 18.2% more haloperidol (p=0.002) than control patients. No drug therapy was required in 19% of pilot patients compared with 2% of controls (p=0.01). Significantly more control (71.4%) than pilot patients (18.8%) were discharged with tapered benzodiazepine therapy (p

Assessment of hypothyroidism in patients with chronic heart failure.

STUDY OBJECTIVE: To determine whether appropriate thyroid function measurements were being conducted in patients receiving care at a multidisciplinary heart failure clinic. DESIGN: Retrospective chart review. SETTING: University-affiliated outpatient clinic. PATIENTS: One hundred ninety-three patients with heart failure. INTERVENTION: Patients enrolled in the heart failure clinic at the Medical University of South Carolina from January 2000-April 2003 were identified. Their medical records were reviewed for demographics, New York Heart Association (NYHA) functional classification, laboratory data, and date of most recent heart failure clinic appointment. MEASUREMENTS AND MAIN RESULTS: The records of 193 patients (43% women) were reviewed. Overall and subgroup analyses were performed based on patient characteristics such as presence of thyroid-stimulating hormone (TSH) level, interval since last heart failure clinic appointment, presence of thyroid replacement therapy, amiodarone use, NYHA functional class, and attending physician. Of the 193 patients, 77 (40%) had appropriate TSH monitoring, whereas 10 (32%) of 31 patients receiving amiodarone had appropriate monitoring. Forty-four (27%) patients not receiving amiodarone had no record of a TSH level. In 22 patients (11%), hypothyroidism was diagnosed and treated, whereas 16 patients (8%) had an abnormal TSH level but received no therapy. CONCLUSION: Forty percent of the 193 patients at this outpatient heart failure clinic received appropriate TSH monitoring. An opportunity exists for protocol implementation and education of pharmacists, nurse practitioners, and physicians concerning appropriate thyroid function monitoring in the heart failure population.

Cost effectiveness of ibutilide with prophylactic magnesium in the treatment of atrial fibrillation.

BACKGROUND: In the Treatment with Ibutilide and Magnesium Evaluation (TIME) study, a retrospective multicentre cohort trial, prophylactic magnesium was found to improve the antiarrhythmic efficacy of ibutilide as demonstrated by an increase in the rate of successful chemical conversion and reduction in the need for direct current cardioversion (DCC). OBJECTIVE: The primary objective of this piggyback cost-effectiveness analysis of the TIME study was to compare the cost per successful conversion of atrial fibrillation (AF) for ibutilide in the presence and absence of magnesium prophylaxis. A secondary objective was to determine whether specific factors predict costs in the conversion of AF. METHOD: The study was conducted from the US hospital-payer perspective. Direct medical costs (USD, 2002 values) including drugs, intravenous admixture and administration, DCC, electrocardiographs and physicians' fees were obtained directly from the provider. Nonparametric bootstrapping was conducted to calculate confidence intervals for the incremental cost-effectiveness ratios. One-way sensitivity analysis was conducted varying efficacy, and drug, hospital and physician costs. Multivariate analysis was conducted to determine whether specific baseline factors were predictors of total cost. RESULTS: Total costs per patient were lower in the ibutilide plus magnesium group compared with ibutilide alone (USD1075 vs USD1201); however, the difference was not statistically significant (p = 0.116). Patients receiving ibutilide plus magnesium had lower DCC costs compared with those receiving ibutilide alone (USD261 vs USD399; p = 0.036), but higher magnesium-associated costs (USD0.50 vs USD0; p < 0.001). Bootstrapping revealed that the ibutilide plus magnesium strategy would result in lower costs and greater efficacy 93.4% of the time. These results remained robust to changes in both cost and efficacy. No baseline factors were found to be independent predictors of total costs. CONCLUSION: Our data suggest that adding prophylactic magnesium to ibutilide may be cost effective, from a US hospital-payer perspective, for the acute conversion of patients in AF or flutter compared with ibutilide alone.

Impact of prophylactic i.v. magnesium on the efficacy of ibutilide for conversion of atrial fibrillation or flutter.

The impact of prophylactic i.v. magnesium on the efficacy of ibutilide for conversion of atrial fibrillation and flutter to normal sinus rhythm was studied. In this multicenter cohort study, all patients in three large, tertiary care centers who received ibutilide for acute chemical conversion of atrial fibrillation or flutter from August 1996 through December 2001 were identified through pharmacy or billing records. Patients who did not receive magnesium before or during ibutilide therapy served as the control group, while those who received magnesium less than two hours before or during ibutilide administration served as the study group. The rate of administration of direct-current cardioversion (DCC) and the occurrence of ventricular arrhythmia were compared between those who did and did not receive magnesium. The rates of successful cardioversion were also assessed. Categorical data were analyzed using chi-square analysis or Fisher's exact test. Demographic data were analyzed using Student's t test. The medical records of 321 patients were analyzed. Successful chemical cardioversion in the study group was approximately 19% higher than in those who did not receive magnesium (p = 0.040). The use of DCC in the group who received magnesium was reduced by approximately 34% (p = 0.045). The conversion rate of atrial fibrillation or flutter with ibutilide was enhanced by magnesium administration (p = 0.040), and the rate of administration of DCC was reduced (p = 0.045) in patients who received magnesium. There was a nonsignificant reduction in the occurrence of ventricular arrhythmias (p = 0.533). The efficacy of ibutilide was enhanced by concomitant administration with intravenous magnesium.

Digoxin in heart failure.

Digoxin is an agent with a long history of use in the management of heart failure; its benefits have just been quantified in recent years. It has long been known that digoxin provides a small amount of inotropic augmentation; however, it is now realized that digoxin also modulates the neurohormonal activation that occurs in heart failure. Although long-term therapy with digoxin does not decrease mortality, it does provide clinical benefit in terms of improved exercise tolerance and decreased hospitalizations across all severities of heart failure. Serum concentrations of digoxin associated with clinical benefits are lower than previously recognized (0.8-1.0 ng/mL). Digoxin toxicity can be easily avoided by maintaining these relatively low serum concentrations, avoiding and aggressively treating hypokalemia, and being mindful of poor renal function and drug interactions that may result in digoxin accumulation.

Cardiovascular drug therapy in women.

Cardiovascular disease has been the leading cause of morbidity and mortality in American women; yet, until recently, there was no mandate to specifically include women in clinical trials of the major cardiovascular drugs. Despite new regulations, there is still a lack of readily available data for the clinician to use when planning drug therapy for women, as many of the drugs in use today were developed and tested prior to the new regulations being in effect. The purpose of this article is to provide advanced practice nurses with the most current information on the use of cardiovascular drugs in women. Information on the unique biological features of women is first presented to provide background material for subsequent sections. This is followed by an explanation of pharmacokinetic processes in women to include information on absorption, distribution, and clearance of drugs. A brief review of the effects of the phases of the menstrual cycle on drug therapy is given and then issues related to the profound physiologic changes in pregnancy and subsequent effects on drug therapy are reviewed. An analysis of the strength of the available evidence on drug therapies in women from the major trials on acute coronary syndromes, heart failure, dyslipidemia, atrial fibrillation, and hypertension is provided. Finally, implications for practice, including recommendations for drug prescription, are summarized.

Parecoxib for parenteral analgesia in postsurgical patients.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy and safety studies, adverse effects, drug interactions, and dosage and administration of parecoxib sodium, a selective cyclooxygenase-2 (COX-2) inhibitor. DATA SOURCES: Information was obtained from MEDLINE searches of the English-language literature (1996-May 2003). Search terms included parecoxib, parecoxib sodium, SC-69124A, and selective cyclooxygenase-2 inhibitor. STUDY SELECTION AND DATA EXTRACTION: We reviewed available literature, which included abstracts, clinical trials, and data on file with the manufacturer. DATA SYNTHESIS: Parecoxib sodium is a novel selective COX-2 inhibitor under development for parenteral administration. It has produced efficacious analgesia following dental, gynecologic, and orthopedic surgery. The adverse effect profile has been compared with that of ketorolac; no statistically significant differences were identified. There are no documented drug interactions when parecoxib is coadministered with midazolam, propofol, or unfractionated heparin. CONCLUSIONS: Parecoxib sodium is in the final stages of Phase III trials and has a favorable safety and efficacy profile. Its place in moderate to severe postsurgical pain management will be further defined when more pharmacoeconomic and postmarketing safety data are available. Theoretical benefits are its lower potential for gastrointestinal adverse effects compared with ketorolac and lower opioid requirements after surgery.

Stability of furosemide in human albumin solution.

OBJECTIVE: To determine the chemical stability of furosemide in human albumin solution over a 28-day period and to assess admixtures for microbiologic contamination. METHODS: Samples were prepared by mixing furosemide injectable solution and 25% human albumin solution in a 1:1 molar ratio. Six bulk containers were prepared and stored in the dark: 3 under refrigeration (approximately 4 degrees C) and 3 at room temperature (approximately 25 degrees C). Study samples were withdrawn from each bulk solution immediately after preparation and at predetermined intervals over the subsequent 28 days. Containers were observed for color change and precipitation against a light and dark background at each sampling interval. Total furosemide concentration was determined using HPLC. Additional vials were prepared and assessed for microbiologic growth at time points corresponding with chemical stability results. RESULTS: A mean of 94.5%+/-1.33% of the initial furosemide concentration remained after 48 hours at room temperature. Under refrigeration, 100.6%+/-1.02% of the initial concentration remained at 14 days. Beyond these respective time points, <90% of the initial furosemide concentration remained. No bacterial or fungal growth was observed. CONCLUSIONS: When combined with 25% human albumin solution and stored under darkness, furosemide is chemically stable and free of microbiologic contamination for 48 hours at room temperature and 14 days under refrigeration.