Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment. RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (-29.8% vs. 3.6%, P<0.001) and non-HDL-C (-10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups. CONCLUSION: The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Supraventricular tachyarrhythmias in patients with a persistent left superior vena cava.

Aims: A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly. This venous anomaly can impact the evaluation and treatment of supraventricular tachyarrhythmia (SVA). The aim of this study was to assess the proportion and characteristics of PLSVC in adult SVA patients. Methods and results: From July 2002 to July 2012, clinical and procedural data from databases of 10 cardiac electrophysiology laboratories in the Yeungnam region of the Republic of Korea were reviewed. Of 6662 adult SVA patients who underwent an EP study or catheter ablation of SVA during the 10-year study period, 18 patients had PLSVC (mean age 47.6 ± 14.8 years, 10 men). The proportion of PLSVC in adult SVA patients was 0.27% (18/6662). SVA type and procedural outcomes of radiofrequency (RF) catheter ablation in these patients were investigated and the results were as follows: successful slow pathway modification in six of seven patients with atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation of accessory pathway in three of four patients with atrioventricular reentrant tachycardia, and successful ablation of atrial tachycardia (cavotricuspid isthmus-dependent in two, septal macroreentry in one, focal from the PLSVC in one) in three of four patients. In one patient with junctional tachycardia, catheter ablation failed. In two patients with atrial fibrillation, catheter ablation was successful. Conclusion: Among adult SVA patients who underwent an EP study or RF catheter ablation during the 10-year study period, 0.27% had PLSVC. The most common type of SVA was AVNRT. The success rate of catheter ablation was 82% in SVA patients with PLSVC. There were no procedure-related complications.

Attenuation of acetylcholine activated potassium current (I KACh) by simvastatin, not pravastatin in mouse atrial cardiomyocyte: possible atrial fibrillation preventing effects of statin.

Statins, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, are associated with the prevention of atrial fibrillation (AF) by pleiotropic effects. Recent clinical trial studies have demonstrated conflicting results on anti-arrhythmia between lipophilic and hydrophilic statins. However, the underlying mechanisms responsible for anti-arrhythmogenic effects of statins are largely unexplored. In this study, we evaluated the different roles of lipophilic and hydrophilic statins (simvastatin and pravastatin, respectively) in acetylcholine (100 µM)-activated K+ current (IKACh, recorded by nystatin-perforated whole cell patch clamp technique) which are important for AF initiation and maintenance in mouse atrial cardiomyocytes. Our results showed that simvastatin (1-10 µM) inhibited both peak and quasi-steady-state IKACh in a dose-dependent manner. In contrast, pravastatin (10 µM) had no effect on IKACh. Supplementation of substrates for the synthesis of cholesterol (mevalonate, geranylgeranyl pyrophosphate or farnesyl pyrophosphate) did not reverse the effect of simvastatin on IKACh, suggesting a cholesterol-independent effect on IKACh. Furthermore, supplementation of phosphatidylinositol 4,5-bisphosphate, extracellular perfusion of phospholipase C inhibitor or a protein kinase C (PKC) inhibitor had no effect on the inhibitory activity of simvastatin on IKACh. Simvastatin also inhibits adenosine activated IKACh, however, simvastatin does not inhibit IKACh after activated by intracellular loading of GTP gamma S. Importantly, shortening of the action potential duration by acetylcholine was restored by simvastatin but not by pravastatin. Together, these findings demonstrate that lipophilic statins but not hydrophilic statins attenuate IKACh in atrial cardiomyocytes via a mechanism that is independent of cholesterol synthesis or PKC pathway, but may be via the blockade of acetylcholine binding site. Our results may provide important background information for the use of statins in patients with AF.