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.

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.

Comparison of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease.

STUDY OBJECTIVE: To compare the lipid-lowering effects of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease. DESIGN: Open label, fixed-dosage, retrospective-prospective, one-way crossover from gemfibrozil to fenofibrate. SETTING: University-affiliated outpatient clinics. PATIENTS: Eighty patients with coronary heart disease with a baseline low-density lipoprotein cholesterol (LDL) level above 130 mg/dl or a triglyceride level of 200 mg/dl or higher who had been receiving gemfibrozil 600 mg twice/day. Thirty-nine (49%) patients had received concomitant therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) for a minimum of 9 months. INTERVENTION: All patients received gemfibrozil 600 mg twice/day for at least 3 months before being switched to fenofibrate 201 mg/day. Patients receiving concomitant statin therapy before crossover continued the statin at the same dosage after crossover. Before crossover, a fasting lipid profile was determined and patients were queried about the side effects of lipid-lowering therapy. A repeat fasting lipid profile was obtained 12 weeks after the crossover. MEASUREMENTS AND MAIN RESULTS: Patients were stratified into those receiving versus those not receiving concomitant statin therapy. In both of these groups, fenofibrate was associated with significantly greater reductions in total cholesterol, LDL, and triglycerides than gemfibrozil (all p < 0.001). In addition, fenofibrate was associated with a significantly greater increase in high-density lipoprotein cholesterol (HDL) than gemfibrozil (p < 0.001). No patients reported new-onset adverse effects after the crossover. CONCLUSIONS: Compared with gemfibrozil, fenofibrate produced significantly greater reductions in total cholesterol, LDL, and triglycerides and significantly greater increases in HDL. These changes were evident in patients receiving and not receiving concomitant statin therapy.

Constipation, polyuria, polydipsia, and edema associated with orlistat.

OBJECTIVE: To report the occurrence of a novel group of adverse effects associated with initiation and rechallenge of orlistat. CASE SUMMARY: A 42-year-old white woman developed symptoms of constipation, polyuria, polydipsia, and increased lower-leg edema after 2 weeks of treatment with orlistat 120 mg 3 times daily. The drug was discontinued for 4 days and the symptoms resolved. On reinstitution of the orlistat treatment, the symptoms reappeared within 2 days. Thereafter, the medication was permanently discontinued. DISCUSSION: Common gastrointestinal adverse reactions associated with orlistat use include fecal urgency and abdominal pain and discomfort. Pedal edema has also been reported to occur, although less frequently. No reports were discovered documenting the occurrence of constipation, polydipsia, and polyuria associated with the use of orlistat. Despite careful consideration of other possible causes of these symptoms, the temporal association between initiation, discontinuation, and rechallenge of orlistat and the patient's symptoms suggest a medication-related adverse event. Based on the Naranjo probability scale, the likelihood that orlistat was the cause of this cluster of adverse effects is possible. CONCLUSIONS: It is important for the healthcare provider to be aware of these adverse effects to promptly evaluate and differentiate between possible causes of similar reactions.

ACE inhibitor-induced bronchial reactivity in patients with respiratory dysfunction.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are often associated with an increased incidence of cough and bronchial responsiveness that may cause further deterioration of patients with impaired pulmonary function. OBJECTIVE: To review the available literature on the incidence of cough and bronchial responsiveness associated with ACE-inhibitor therapy in patients with asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). DATA SOURCES: Literature was accessed through MEDLINE (1985-September 2001). Key search terms included cough, bronchospasm, asthma, congestive heart failure, chronic obstructive pulmonary disease, ACE inhibitors, and angiotensin II receptor blockers. DATA SYNTHESIS: The literature reports several cases of increased bronchial responsiveness associated with ACE inhibitors. Larger, controlled studies evaluating the increased risk in patients with pulmonary dysfunction are limited. Data from these trials are summarized in this article. CONCLUSIONS: The literature shows that patients with primary airway disease such as asthma and COPD are not at an increased risk of developing cough or bronchoconstriction as a result of ACE-inhibitor therapy. Despite the ability of ACE inhibitors to improve exercise tolerance, perfusion, and gas transfer, patients with CHF may be at higher risk of developing cough than the general population. Whether this cough is attributed to ACE inhibition or increased left-ventricular dysfunction remains uncertain. If increased bronchial responsiveness does occur, angiotensin II receptor antagonists are another reasonable option.

Amiodarone vs. sotalol as prophylaxis against atrial fibrillation/flutter after heart surgery: a meta-analysis.

BACKGROUND: The incidence of supraventricular arrhythmias remains high following open-heart surgery. The most common of these arrhythmias are atrial fibrillation and flutter (AFF), for which treatment is not well defined. Recent studies have focused on prophylactically treating patients in an attempt to reduce postoperative AFF. Several studies have shown that sotalol and amiodarone are both effective in reducing AFF following heart surgery. However, no studies have been done comparing both drugs. METHODS: A meta-analysis was done to compare the efficacy of sotalol and amiodarone after bypass graft surgery. Randomized controlled trials were included if patients were clearly monitored, and the incidence of AFF was noted. Ten studies were included in the final analysis. RESULTS: Both amiodarone and sotalol were more effective than placebo treatment in reducing the incidence of postoperative AFF. However, when the data were pooled, no differences were noted between amiodarone and sotalol for efficacy (sotalol, - 21.5%; 95% confidence interval [CI], - 28.3 to - 14.6; amiodarone, - 14.1%; CI, - 20.1 to - 8.1), length of stay (sotalol, - 0.13 d; CI, - 0.33 to 0.07 d; amiodarone, - 0.18; CI, - 0.38 to 0.02 d), or adverse drug reactions causing drug termination (sotalol, 9.7%; CI, 0.086 to 19.3; amiodarone, 1.95%; CI, - 0.48 to 4.38). CONCLUSIONS: This data would suggest that either drug could be used in a prophylactic regimen to reduce the incidence of AFF following heart surgery.