Effect of omega-three polyunsaturated fatty acids on inflammation, oxidative stress, and recurrence of atrial fibrillation.

The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin [IL]-6, IL-8, IL-10, tissue necrosis factor alpha, monocyte chemoattractant protein-1, and vascular endothelial growth factor), N-terminal-pro-brain-type natriuretic peptide, and oxidative stress (urinary F2-isoprostanes). AF recurred in 74 patients (58.7%) randomized to n-3 PUFAs and in 30 patients (46.9%) who received placebo; time to recurrence of AF did not differ significantly in the 2 groups (hazard ratio 1.20; 95% confidence interval 0.76 to 1.90, adjusted p = 0.438). Compared with placebo, n-3 PUFAs did not result in clinically meaningful changes in concentrations of inflammatory markers, N-terminal-pro-brain-type natriuretic peptide or F2-isoprostanes. In conclusion, in patients with paroxysmal or persistent AF, treatment with n-3 PUFAs 4 g/day did not reduce the recurrence of AF, nor was it associated with clinically important effects on concentrations of markers of inflammation and oxidative stress. (Clinical trial registration number, NCT 00552084.).

Role of orally available antagonists of factor Xa in the treatment and prevention of thromboembolic disease: focus on rivaroxaban.

Interpatient variability in the safety and efficacy of oral anticoagulation with warfarin presents several challenges to clinicians, thus underscoring the emergent need for new orally available anticoagulants with predictable pharmacokinetic and pharmacodynamic profiles and ability to target circulating clotting factors. Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome. At doses used in phase 2 and 3 clinical trials, rivaroxaban and apixaban demonstrated a predictable onset of effect, maximal plasma concentration, and half-life that was unaffected by age, renal, or hepatic disease. In clinical trials for the treatment and prevention of venous thromboembolism, rivaroxaban and apixaban produced equivalent or superior reductions in the development or progression of venous thromboembolism compared with either low molecular weight heparin or warfarin. Trials comparing the efficacy of rivaroxaban or apixaban to standard therapy for stroke prophylaxis in patients with atrial fibrillation are in process. Rivaroxaban, the sentinel compound in this class, is already approved in the European Union and Canada. It is likely to be approved for use in the United States in 2010.

A case report of atrial fibrillation potentially induced by hydroxycut: a multicomponent dietary weight loss supplement devoid of sympathomimetic amines.

Multicomponent dietary weight loss supplements comprise the single largest segment of herbal preparations available to the public. As a result of limited de novo regulatory oversight, supplement-related adverse events are underreported secondary to the lack of adequate pharmacodynamic, pharmacokinetic, and clinical data. Here we report the case of an obese 63-year-old caucasian female with a 2-day history of symptomatic paroxysmal atrial fibrillation (AF) with rapid ventricular response following a 2-week course of therapy with hydroxycut, a multicomponent dietary weight loss supplement devoid of sympathomimetic amines. Upon presentation, the patient received 2 doses of intravenous diltiazem, was loaded with intravenous digoxin, and spontaneously converted to normal sinus rhythm 36 hours following her last dose of the product. Epigallocatechin (EGCG), a principal ingredient in the hydroxycut preparation is the suspected causative component. EGCG blocks the atrial-specific KCNA5 potassium channel. Loss of KCNA5 function has been reported in patients with familial lone AF. Thus, causal relationship between hydroxycut and AF in this patient is probable. Given the serious risks associated with AF, patients at risk of developing AF should avoid dietary supplements containing EGCG until more information on the adverse effects of EGCG is known.

Hemodynamic impact of an ephedra-free multicomponent weight-loss supplement.

PURPOSE: The effect of Metabolife Ephedra-Free on blood pressure (BP) and hemodynamics was studied. METHODS: Healthy volunteers were randomly assigned to take a single dose of Metabolife Ephedra-Free or matching placebo and then crossed over to the opposite treatment after a seven-day washout period. BP was measured at baseline and one, three, and five hours after administration. Cardiac index, systemic vascular resistance index (SVRI), and total thoracic fluid content were determined in a subgroup of subjects. RESULTS: Twenty patients (mean +/- S.D. age, 24.8 +/- 1.9 years) completed the study. No significant differences in systolic or diastolic BP were found between the Metabolife Ephedra-Free and placebo groups. In the subgroup (n = 8), SVRI was higher (but not significantly so) in the Metabolife Ephedra-Free group than in the placebo group at one hour (2162.5 +/- 421.1 versus 1934.6 +/- 344.2 dyn x sec x cm(-5) x m(2)); the difference was significant at five hours (1981.6 +/- 293.3 versus 1765.1 +/- 340.3 dyn x sec x cm(-5) x m(2)). CONCLUSION: Single doses of Metabolife Ephedra-Free did not affect BP in healthy young volunteers. SVRI did not exceed the normal range but was elevated at five hours compared with SVRI in placebo recipients.

Electrocardiographic effects of an Ephedra-Free, multicomponent weight-loss supplement in healthy volunteers.

STUDY OBJECTIVE: Metabolife 356, an ephedra-containing weight-loss product, substantially increases the corrected QT (QTc) interval. Metabolife Ephedra Free, a similar supplement, contains caffeine and extracts of green tea, garcinia cambogia, and yerba mate. Its electrocardiographic (ECG) effects are not known. Therefore, we sought to determine the effect of this supplement on the QTc interval. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: University of Connecticut, Storrs Campus. SUBJECTS: Twenty healthy volunteers. Intervention. A single capsule containing half the normal recommended dose of Metabolife Ephedra Free or matching placebo was administered in crossover fashion, with a 7-day washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Baseline and three postdose ECG measurements were obtained, and QTc intervals were measured over a 5-hour study period. No significant differences in the QTc interval or other ECG variables were observed between the Metabolife Ephedra Free and placebo groups. CONCLUSION: At half the recommended single dose, Metabolife Ephedra Free does not affect the QTc interval or other ECG variables over 5 hours. Dose-response studies and studies of longer duration should be conducted.

Inappropriate implantable cardioverter defibrillator discharge following consumption of a dietary weight loss supplement.

This report describes the clinical course of a 40-year-old female who experienced repetitive ICD firing after consuming Metabolife 356, a multicomponent dietary weight loss supplement. Following the initiation of Metabolife 356, the patient experienced four shocks over a 3 day period with two 30 J shocks being delivered sequentially. Interrogation of the device revealed atrial tachycardia with 1:1 AV conduction at a rate of 240 beats/min. Metabolife 356 was discontinued and the dosage of sotalol was increased to 120 mg twice daily without recurrence of ICD discharge.

Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial.

CONTEXT: Metabolife 356, a multicomponent dietary supplement containing ephedra and caffeine (DSEC) in addition to several other components, is the top-selling dietary weight loss supplement. Given its common use, anecdotal reports of cardiovascular and cerebrovascular adverse events, and paucity of safety data, further research with this DSEC was warranted. OBJECTIVE: To determine the impact of the DSEC on corrected QT (QTc) interval duration and systolic blood pressure (SBP). DESIGN: Randomized, double-blind, placebo-controlled, crossover study conducted from January to May 2003. SETTING AND PARTICIPANTS: Fifteen healthy volunteers (mean [SD] age, 26.7 [2.52] years; weight, 72.7 [14.93] kg), 6 (40%) of whom were women, recruited from the University of Connecticut, Storrs campus. INTERVENTION: A single dose of the DSEC (containing 19 ingredients including ephedra [12 mg] and caffeine [40 mg]) or matching placebo were administered in a crossover fashion with a 7-day washout period between treatments. MAIN OUTCOME MEASURES: Maximal QTc interval and SBP assessed at 1, 3, and 5 hours after dosing for the DSEC relative to placebo. RESULTS: Individuals receiving the DSEC had a longer maximal QTc interval (mean [SD], 419.4 [11.8] vs 396.1 [15.7] milliseconds; P<.001) and higher SBP (mean [SD], 123.5 [10.98] vs 118.93 [9.62] mm Hg; P =.009) compared with placebo. Participants who received the DSEC were more likely to experience a QTc interval increase of at least 30 milliseconds vs placebo (8 individuals [53.3%] vs 1 individual [6.7%]; relative risk, 2.67 [95% confidence interval, 1.40-5.10]). There were no significant sex-related differences. CONCLUSIONS: The ephedra- and caffeine-containing dietary supplement Metabolife 356 increased the mean maximal QTc interval and SBP. Since the actual ingredient or ingredients in Metabolife 356 responsible for these findings are not known, patients should be instructed to avoid this and similar dietary supplements until more information is known about their safety.