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Biomedical subjects

Daniel E Hilleman

Publications and source records attributed to Daniel E Hilleman.

At least 19 recordsLinked to original sources

Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients.

OBJECTIVE: To perform an analysis of healthcare resource utilization with intensive insulin therapy, which has recently been shown to reduce morbidity and mortality rates of mechanically ventilated critically ill patients in a surgical intensive care unit. DESIGN: A post hoc cost analysis. SETTING: Surgical intensive care unit. PATIENTS: Patients were 1548 mechanically ventilated patients admitted to a surgical intensive care unit. INTERVENTIONS: A post hoc cost analysis was conducted based on data collected prospectively as part of a large randomized controlled trial. The analysis performed was a healthcare resource utilization analysis in which the cost of hospitalization in the intensive care unit was determined based on length of stay and the frequency of crucial cost-generating morbid events occurring in the intensive and conventional insulin treatment groups. Sensitivity analyses were performed to evaluate the robustness of the findings. Discounting of costs was not performed as treatment was limited to the intensive care stay and follow-up was not continued beyond hospitalization. MEASUREMENTS AND MAIN RESULTS: In the intensive treatment group, total treatment cost was 109,838 Euros (144 Euros per patient). In the conventional treatment group, total treatment cost was 56,359 Euros (72 Euros per patient). The excess cost of intensive insulin therapy was 72 Euros per patient. The total hospitalization cost in the intensive treatment group was 6,067,237 Euros (7931 Euros per patient) compared with 8,275,394 Euros (10,569 Euros per patient) in the conventional treatment group. The excess cost of intensive care unit hospitalization in the conventional vs. intensive treatment group was 2638 Euros per patient. These intensive care unit benefits were not offset by additional costs for care on regular wards. CONCLUSIONS: Intensive insulin therapy, which reduces morbidity and mortality rates of mechanically ventilated patients admitted to a surgical intensive care unit, is associated with substantial cost savings compared with conventional insulin therapy.

Belgium↗

Pharmacoeconomic considerations with statin therapy.

Statins have been shown to reduce morbidity and mortality in patients with and without coronary heart disease, and in patients with elevated and normal or average cholesterol levels. Economic evaluations of these mortality trials have demonstrated statins to be cost-effective. As these trials were placebo comparisons, their results are now of limited use in guiding the drug therapy selection process. The more relevant questions today are focused on ways of optimising statin therapy. More recent studies have found that more intensive statin therapy, using high doses of these agents that produce substantially greater reductions in low-density lipoprotein cholesterol, are associated with greater benefit than less intensive statin therapy. These trials suggest that statins with greater efficacy in reducing low-density lipoprotein cholesterol, would be preferred over less effective statins. So far, economic analyses of these comparative studies have not been published. These economic studies are needed to support formulary and drug therapy selection decisions regarding statins.

Adult↗

Randomized, double-blind, crossover comparison of amlodipine and valsartan in african-americans with hypertension using 24-hour ambulatory blood pressure monitoring.

STUDY OBJECTIVE: To compare the efficacy of amlodipine and valsartan in African-American patients with hypertension using ambulatory blood pressure monitoring (ABPM). DESIGN: Prospective, randomized, double-blind, crossover comparison study. SETTING: University-affiliated cardiac center clinic. PATIENTS: Twenty African-Americans (12 men, 8 women), with a history of uncomplicated hypertension (blood pressure > 140/90 mm Hg). INTERVENTION: Patients were randomized to receive amlodipine 5 or 10 mg/day or valsartan 80 or 160 mg/day for 8-10 weeks, depending on response. Dosages were titrated to achieve a blood pressure of 140/90 mm Hg or below. For patients whose blood pressures were not controlled, hydrochlorothiazide 12.5 mg/day was added to their regimens. Patients then underwent 24-hour ABPM. After an intervening washout period during which baseline blood pressure was reestablished, patients received the other treatment. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD baseline blood pressure before the two ABPM periods were 155 +/- 12/100 +/- 8 mm Hg and 156 +/- 11/101 +/- 9 mm Hg, respectively. Fifteen (75%) patients achieved goal blood pressure with amlodipine and 14 (70%) with valsartan (p=0.62). Final daily dosages were as follows: amlodipine 5 mg in nine patients, 10 mg in five patients, and 10 mg plus hydrochlorothiazide in six patients; valsartan 80 mg in nine patients, 160 mg in four patients, and 160 mg plus hydrochlorothiazide in seven patients. Ambulatory blood pressure monitoring was not completed in three patients due to adverse effects: headache and dizziness (one patient each, amlodipine and valsartan) and hyperkalemia (one patient, valsartan). Four patients (20%) in each treatment group had drug-related adverse effects. Results of ABPM including averages for 24-hour, daytime, nighttime, first 4 hours, and last 8 hours, and trough:peak ratios were not significantly different between the amlodipine- and valsartan-based treatments. CONCLUSION: Based on both clinic blood pressure measurements and ABPM data, amlodipine and valsartan produced similar reductions in blood pressure in African-American patients with uncomplicated hypertension.

Adult↗

Reteplase: a review of its use in the management of thrombotic occlusive disorders.

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based) rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.

Arterial Occlusive Diseases↗

Antiplatelet drug resistance: not ready for prime time.

Antiplatelet drug therapy reduces vascular events in a wide range of patients. Although antiplatelet drug resistance is becoming well documented, a universal definition has not been established. This lack and the lack of standardized measures of platelet function make estimation of the prevalence of antiplatelet drug resistance difficult. Mounting evidence suggests that antiplatelet drug resistance is associated with adverse clinical outcomes, which have been assessed in patients with coronary artery disease, myocardial infarction, cerebrovascular disease, and peripheral vascular disease. Patients with antiplatelet drug resistance have significantly more vascular events than patients without such resistance. However, there are no guidelines for the treatment of antiplatelet drug resistance. Although point-of-care platelet-function testing makes screening for resistance feasible, routine screening should not be standard practice until data regarding the management of antiplatelet drug resistance are available.

Blood Platelets↗

Pharmacological management of atrial fibrillation following cardiac surgery.

Atrial fibrillation (AF) is the most common complication following coronary artery bypass graft surgery (CABG). Post-CABG AF occurs most commonly on the second postoperative day and declines in incidence thereafter. A number of risk factors have been found to be associated with a higher frequency of post-CABG AF. These risk factors include advanced age, a prior history of AF, hypertension, and heart failure. Postoperative complications--including low cardiac output, use of an intra-aortic balloon pump, pneumonia, and prolonged mechanical ventilation--are also associated with higher rates of post-CABG AF. Post-CABG AF increases the risk of stroke, and the length and cost of hospitalization. Prophylactic administration of conventional beta-adrenoceptor antagonists (beta-blockers) or sotalol produces a consistent and significant reduction in the incidence of post-CABG AF; however, results with prophylactic amiodarone or magnesium are less consistent. Termination of post-CABG AF, once it occurs, can be accomplished with a number of antiarrhythmic agents. Ibutilide has been the most widely studied agent for this indication. Sotalol is not indicated for cardioversion of AF and has not been studied in the post-CABG setting. Electrical cardioversion and biatrial pacing have also been used to terminate post-CABG AF. Ventricular rate is best controlled with beta-blockers and calcium channel antagonists. Esmolol has a rapid onset of action and is easily titrated to effect. Digoxin can control the ventricular rate, but has a slow onset of action. There are limited data available to guide decisions regarding the optimal management of post-CABG AF.

Adrenergic beta-Antagonists↗

New treatment options in COPD.

OBJECTIVE: To review the role of long-acting bronchodilators in the treatment of chronic obstructive pulmonary disease (COPD), including the importance of treatment adherence. SUMMARY: Overall, clinical trials show that compared with placebo and ipratropium, tiotropium significantly improves spirometric measures, increases quality-of-life scores, and is associated with fewer exacerbations. In addition, compared with salmeterol, tiotropium is associated with greater improvements in spirometric measures and clinically meaningful increases in quality-of-life measures. In comparison with either fluticasone or salmeterol alone, the fluticasone/salmeterol combination is associated with statistically greater improvement in spirometric and dyspnea measures; however, the combination is not associated with fewer exacerbations than either fluticasone or salmeterol used by itself. CONCLUSIONS: The 2003 update to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommends regular treatment with long-acting bronchodilators for maintenance COPD therapy because of superior effectiveness and convenience compared with short-acting bronchodilators. The results from trials presented in this article demonstrate that inhaled tiotropium is effective in treating COPD and might be considered as a first-line agent for maintenance therapy in view of its outcomes data. The convenience of once-daily administration would probably contribute to patient adherence and thus to the overall efficacy of this agent.

Bronchodilator Agents↗

Low high-density lipoprotein cholesterol is associated with impaired endothelial function in Asian Indians.

This study was designed to assess the relationship between plasma lipid levels and endothelial function in Asian Indians without cardiovascular risk factors living in the United States. While traditional risk factors do not account for the increased incidence of coronary heart disease (CHD) in Asian Indians, low high-density lipoprotein (HDL) cholesterol, elevated triglycerides, elevated lipoprotein (a), and insulin resistance are consistently found in Asian Indians with CHD. Endothelial function was measured in 86 healthy Asian Indians (mean age 33 years) free of cardiac risk factors with LDL levels<160 mg/dL. Subjects were divided into two groups on the basis of HDL levels (low HDL<40 mg/dL and normal HDL-40 mg/dL). Endothelial function during reactive hyperemia was significantly impaired in Asian Indians in the low HDL group. After covariate adjustment, NTG-induced brachial vasodilation was not different between patients in the two HDL groups. These data indicate that low HDL is associated with endothelial dysfunction in this population.

Adult↗

Amiodarone versus sotalol for the treatment of atrial fibrillation after open heart surgery: the Reduction in Postoperative Cardiovascular Arrhythmic Events (REDUCE) trial.

OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study compared the efficacy and safety of amiodarone and sotalol in the prevention of atrial fibrillation (AF) following open heart surgery. BACKGROUND: The incidence of supraventricular arrhythmias following open heart surgery ranges from 20% to 40%, with AF being the most common. Both amiodarone and sotalol have been shown to be effective in reducing postoperative arrhythmias, but no direct comparison of these agents has been conducted. METHODS: A total of 160 patients were randomized, of whom 134 underwent coronary artery bypass graft surgery (CABG) alone, 17 underwent CABG and concomitant aortic valve replacement surgery (AVR), 9 underwent AVR only, and 1 patient's surgery was canceled. Patients with signs or symptoms of congestive heart failure (CHF), ejection fraction < or =30%, estimated creatinine clearance <30 mL/min, or serum creatinine > or =2.5 mg/dL were excluded. Patients were randomized to receive either sotalol 80 mg 2 times per day (n = 76) or intravenous amiodarone 15 mg/kg over 24 hours followed by oral amiodarone 200 mg 3 times per day (n = 83). Study drug was started at the time of surgery and continued for 7 days or until discharge, whichever came first. RESULTS: AF occurred in 17% of patients randomized to amiodarone and 25% of the patients randomized to sotalol (P =.21). However, the duration of AF was significantly shorter in amiodarone-treated patients (169 +/- 224 min) compared to sotalol treated patients (487 +/- 505 min; P =.04). In a subgroup analysis, the incidence of AF in patients undergoing AVR or CABG with AVR was significantly less with amiodarone (1/15, 7%) compared to sotalol (9/11, 82%) (P <.001). Blood pressure was lower immediately after surgery with amiodarone but comparable to sotalol at 24 hours. Of the hemodynamic indices measured, only stroke volume was significantly lower in patients randomized to sotalol at 24 hours (P =.035). CONCLUSIONS: Amiodarone and sotalol share similar efficacy and safety in reducing postoperative AF. Hemodynamic effects were similar between both drugs at 24 hours, with the exception that stroke volume was lower in sotalol-treated patients. In patients undergoing more complex surgery, postoperative AF occurred more frequently with sotalol than with amiodarone.

Aged↗

Comparison of conservative and aggressive smoking cessation treatment strategies following coronary artery bypass graft surgery.

PURPOSE: Patients who continue to smoke following coronary artery bypass graft surgery (CABG) have substantially poorer outcomes than patients able to stop smoking after CABG. This study evaluated the effectiveness of two smoking cessation treatment strategies in patients undergoing CABG. METHODS: Two smoking cessation treatment strategies were compared in smokers who underwent CABG. In the conservative treatment strategy, smokers undergoing CABG were followed up prospectively at monthly intervals. Patients who started smoking again at any time in the year following CABG were asked to enroll in an 8-week smoking cessation program. In the aggressive treatment strategy, smokers undergoing CABG were asked to enroll in an 8-week smoking cessation program starting immediately after hospital discharge. The structure and makeup of the smoking cessation program used in the conservative and aggressive treatment strategies were identical. The primary study outcome was smoking status assessed by self-report and confirmed by expired carbon monoxide at 1.5 months, 3 months, 6 months, and 12 months after surgery. RESULTS: Nineteen patients were enrolled in the conservative treatment strategy, with 2 patients unavailable for follow-up prior to the first follow-up visit. Of the remaining 17 patients, 14 patients (82%) resumed smoking at an average of 10.3 weeks after CABG. Eleven of these 14 patients (79%) agreed to participate in the smoking cessation program. Based on evaluable patients, 10 of the 17 patients (59%) in the conservative strategy group were not smoking at the 12-month follow-up. Twenty patients were enrolled in the aggressive treatment strategy. All patients agreed to participate in the smoking cessation program. All patients were available for follow-up. At the 12-month follow-up, 17 of 29 patients (85%) in this treatment strategy were not smoking. Point prevalence and continuous abstinence cessation rates were significantly greater in the aggressive treatment strategy compared to the conservative treatment strategy at all follow-up intervals after CABG. CONCLUSION: Based on our findings in a small number of patients, an aggressive smoking cessation intervention is associated with a superior smoking cessation rate compared to a conservative treatment strategy in smokers undergoing CABG. A larger study will be needed to confirm that an early aggressive smoking cessation intervention should be provided to all smokers undergoing CABG.

Aged↗

Nebulized opioids use in COPD.

OBJECTIVE: To evaluate the role of nebulized opioids in COPD. METHODS: A MEDLINE search was completed to obtain pertinent clinical literature. Key search terms included the following: nebulizer, opioids, COPD, dyspnea, morphine, and hydromorphone. RESULTS: Currently, the evidence in the literature is lacking regarding placebo-controlled studies to support nebulized morphine for the relief of dyspnea in patients with COPD. The studies reviewed varied considerably in the dose, opioid used, administration schedule, and methodology. One study found improved exercise capacity in 11 patients not reproducible in a larger sample, and another study found benefit in 54 terminal patients. All other studies found no benefit. CONCLUSIONS: The recently published Global Initiative for Lung Disease guidelines have specifically stated that opioids are contraindicated in COPD management due to the potential respiratory depression and worsening hypercapnia. Nebulized opioids should be discouraged, as current data do not support their use.

Administration, Inhalation↗

Angiotensin-converting enzyme inhibitors and stroke risk: benefit beyond blood pressure reduction?

Hypertension, a leading cause of morbidity and mortality, accounts for 25-49% of all strokes. Randomized placebo-controlled trials primarily with diuretics and beta-blockers administered in patients with hypertension have demonstrated a 38% reduction in primary stroke. Placebo-controlled trials with angiotensin-converting enzyme (ACE) inhibitors have not been conducted in patients with hypertension. However, in a meta-analysis of four placebo-controlled trials of ACE inhibitors in patients with coronary heart disease and/or diabetes mellitus, the overall risk of primary stroke was significantly reduced. Results of the Heart Outcomes Prevention Evaluation trial, which produced a substantial reduction in stroke with an apparently small reduction in blood pressure, suggest that the benefit of ACE inhibitors may be related to their effects on the renin-angiotensin-aldosterone system more than on blood pressure reduction. In active-control comparisons in patients with hypertension, ACE inhibitors have demonstrated reductions in primary stroke risk similar to reductions with diuretics, beta-blockers, and calcium channel blockers. The data suggest that for primary prevention of stroke antihypertensive therapy should be individualized in patients. Relatively few data are available concerning the benefit of antihypertensive therapy in the secondary prevention of stroke. In patients who had experienced a stroke or transient ischemic attack, therapy with a diuretic or a combination of a diuretic plus an ACE inhibitor could be recommended based on available outcome studies conducted in this patient population. It is premature to conclude that the benefit of ACE inhibitor therapy in primary or secondary prevention of stroke is an effect independent of blood pressure reduction. Hypertension detection, treatment, and control in patients still must be the principal focus of clinicians for both primary and secondary prevention of stroke.

Aged↗

Cost of a pharmacist-directed intervention to increase treatment of hypercholesterolemia.

STUDY OBJECTIVE: To evaluate the cost of a pharmacist-directed intervention that prompts physicians to treat hypercholesterolemia more aggressively in patients with coronary heart disease (CHD). METHODS: Health care resource use and CHD outcomes were evaluated for 612 patients with CHD followed for 2 years after an index hospitalization for an ischemic event. After discharge, the physicians of 309 patients who had been admitted from January 1--March 31, 1999, were contacted by telephone and mail concerning lipid profiles and statin therapy. These patients were the intervention group. Controls were 303 patients admitted from October 1--December 31, 1998; their physicians were not contacted. Costs of the physician-prompting intervention, clinic visits, laboratory tests, statin drugs, and CHD outcomes were compared between these two patient groups. RESULTS: The number of clinic visits, laboratory tests, and statins prescribed was significantly greater for the intervention group versus the controls. A significantly higher percentage of patients in the intervention group (55%) than in the control group (18%) achieved their National Cholesterol Education Program target low-density lipoprotein cholesterol level and had significantly better CHD outcomes. The cost of the physician-prompting intervention (pharmacist salaries, postage, telephone calls) was $102,941. For patients in the intervention and control groups, respectively, the cost of statin therapy was $352,365 and $200,087, the cost of clinic visits and laboratory tests $48,097 and $27,367, and the cost of coronary heart disease outcomes, such as myocardial infarction, coronary artery bypass graft, percutaneous transluminal and coronary angioplasty, $1,073,495 and $1,741,220. The total cost was $1,576,898 and $1,968,674, respectively, for patients in the intervention and control groups. Net savings was $1394/patient over the 2-year period. CONCLUSION: A relatively simple physician-prompting intervention involving patients with CHD significantly improved the use of lipid testing and statin therapy. Improved use of statins was associated with better CHD outcomes. As a result, the physician-prompting intervention was associated with cost savings. This intervention should be implemented for patients with CHD discharged after hospitalization for an ischemic event.

Case-Control Studies↗

Impact of nesiritide on health care resource utilization and complications in patients with decompensated heart failure.

STUDY OBJECTIVE: To determine the impact of nesiritide on health care resource utilization and complications in patients hospitalized with decompensated heart failure. DESIGN: Retrospective case-control study. SETTING: United States hospitals. PATIENTS: Two hundred sixteen patients hospitalized for decompensated heart failure. MEASUREMENTS AND MAIN RESULTS: One hundred eight patients who received a nesiritide infusion for a minimum of 12 hours during the first 48 hours after hospital admission were matched with 108 patients not receiving nesiritide. Health care resource utilization, consisting of hospital length of stay (LOS), rate of rehospitalization within 90 days, concomitant drugs administered, and laboratory and diagnostic tests, was determined for each hospital admission. Rates of adverse events also were recorded. Patients receiving nesiritide had a significantly shorter LOS in a critical care unit (p=0.03). General medical ward or step-down unit LOS was not different between the treatment groups. A favorable trend toward a lower rate of rehospitalization over the 90-day follow-up period was observed with nesiritide (p=0.07). The number of patients who developed life-threatening ventricular arrhythmias and hypotension was similar for both treatment groups. However, in patients receiving nesiritide, significantly less atrial fibrillation (p=0.03) and renal dysfunction (p=0.04) occurred compared with patients not receiving nesiritide. CONCLUSION: Nesiritide therapy is associated with significant reductions in both health care resource utilization and complications in patients with decompensated heart failure.

Aged↗

Fingernail clubbing and chromonychia associated with the use of angiotensin II receptor blockers.

Fingernail clubbing and discoloration frequently indicate serious pulmonary, cardiovascular, and gastrointestinal pathologies. A 76-year-old Caucasian man developed clubbing of the fingernails and discoloration of both the fingernails and toenails after 27 days of treatment with the angiotensin II receptor blocker (ARB) losartan 50 mg/day. Even though this therapy was switched to valsartan, the nail changes persisted for another 6 months. The patient's therapy then was changed to captopril, and the changes gradually subsided over 17 months. An extensive literature search revealed no reports of this effect in association with ARBs. However, one manufacturer had received spontaneous reports. Despite careful consideration of other possible causes of the patient's symptoms, the temporal association with the start and discontinuation of ARB therapy suggests a possible drug-related adverse event.

Aged↗

Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography.

BACKGROUND: Contrast-induced nephropathy (CIN) after coronary angiography is associated with increased morbidity and mortality rates. Preliminary studies with N-acetylcysteine (NAC) have found conflicting results in the prevention of CIN in patients undergoing coronary angiography. This study was designed to evaluate the efficacy and safety of NAC in the prevention of CIN in patients undergoing coronary angiography. METHODS: This study was prospective, randomized, double-blind, and placebo-controlled. Patients referred for elective coronary angiography with a baseline creatinine clearance level <50 mL/min and serum creatinine >1.2 mg/dL were randomly assigned to 1500 mg NAC or placebo, starting the evening before angiography and given every 12 hours for 4 doses. The primary study end point was the development of CIN, which was defined as an increase of >0.5 mg/dL or an increase of > or =25% in serum creatinine over baseline within 48 hours of angiography. Secondary end points included changes in serum creatinine and blood urea nitrogen, requirement of dialysis, side effects of study medication, hospital length of stay, and hospital charges. RESULTS: CIN occurred in 8.2% (4/49) of patients taking NAC and 6.4% (3/47) of patients taking placebo. Changes in BUN and serum creatinine from baseline were not significantly different in the two treatment groups. Baseline BUN and volume of contrast were the only independent predictors of CIN. More patients with diabetes had development of CIN (5/43; 12%) compared with nondiabetic patients (2/52; 4%), but the difference was not significant (P =.15). The incidence of CIN in diabetic patients was not different in the two treatment groups. No patient with development of CIN required dialysis. Side effects (mostly gastrointestinal) occurred in 16% of patients taking NAC and in none of the patients taking placebo. Length of stay and hospital charges were not different between the treatment groups. CONCLUSIONS: In patients with reduced renal function undergoing elective coronary angiography, NAC does not reduce the risk of CIN.

Acetylcysteine↗

Esmolol versus diltiazem in atrial fibrillation following coronary artery bypass graft surgery.

PURPOSE: Atrial fibrillation (AF) is the most common arrhythmic complication following coronary artery bypass graft surgery (CABG). The efficacy and safety of esmolol and diltiazem were compared in patients with post-CABG AF. METHODS: This study was a retrospective medical record review of consecutive patients with post-CABG AF > or =15 min in duration with a ventricular rate > or =110 b.p.m. who received either i.v. esmolol (n = 59) or i.v. diltiazem (n = 48) with or without concomitant digoxin therapy at a single university-affiliated teaching hospital. Treatment success was defined as either cardioversion to sinus rhythm or a reduction in the ventricular rate to < or =90 b.p.m. at 24 h after the start of therapy. Time to treatment success and the occurrence of adverse effects were considered secondary outcomes. RESULTS: A total of 107 patients with post-CABG AF were treated with i.v. esmolol (n = 59) or i.v. diltiazem (n = 48). The mean maximum dose of esmolol and diltiazem were 115 +/- 38 microg/kg/min and 11.2 +/- 3.5 mg/h, respectively. The average duration of the esmolol and diltiazem infusions were 19.3 +/- 8.5 h and 20.1 +/- 11.3 h, respectively. Based on the combined efficacy endpoint of cardioversion or ventricular rate control, esmolol was significantly more effective than diltiazem (90% vs 77%; p = 0.038). Time to treatment success was significantly better for esmolol than diltiazem at all time points (1, 2, 4, 6, 12, and 24 h post-treatment). The overall incidence of adverse effects was 44% with esmolol and 60% with diltiazem (p = 0.04). Rates of drug discontinuance for adverse effects were significantly less for esmolol (20%) compared with diltiazem (38%) (p = 0.04). CONCLUSIONS: Esmolol is significantly more effective than diltiazem in the management of post-CABG AF. More patients converted to sinus rhythm with esmolol as compared to diltiazem. Esmolol was associated with fewer adverse effects than diltiazem, including adverse effects leading to drug discontinuance. Due to study design limitations (retrospective data collection), an adequately powered randomised, controlled trial is needed to confirm these preliminary findings.

Adrenergic beta-Antagonists↗

Pharmacologic treatment of chronic obstructive pulmonary disease: past, present, and future.

Pharmacologic treatment of chronic obstructive pulmonary disease (COPD) has evolved considerably during the past several decades. Initial treatment of the disease was accomplished primarily through antibiotics, mucolytic agents, and nonselective sympathomimetic agents. Up-to-date treatment guidelines stratified according to strength of evidence are published in the National Heart, Lung, and Blood Institute-World Health Organization workshop report on the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Current drug therapy for stable COPD focuses primarily on bronchodilation through inhaled beta2-agonists and anticholinergic agents, immunization, and elimination of smoking as a risk factor. Although many pharmacologic agents are available to treat COPD, no drug has demonstrated effectiveness in halting progression of the disease. Rather, the goal of drug therapy at this time is to maintain control of symptoms and prevent COPD exacerbations. Compared with asthma, research into treatment for COPD has been minimal. However, a long-acting anticholinergic agent, tiotropium, has received approval status by the United States Food and Drug Administration. The drug has been shown to improve spirometric parameters, quality of life, and utilization of health care resources. In addition, several new targets for the treatment of COPD are being studied, and a few agents, including some that theoretically may slow functional decline in patients with COPD, are in development.

Adrenal Cortex Hormones↗