Colchicine in Patients with Chronic Coronary Disease.

BACKGROUND: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited. METHODS: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke. RESULTS: A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31). CONCLUSIONS: In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Early repolarization is associated with symptoms in patients with type 1 and type 2 long QT syndrome.

BACKGROUND: Early repolarization (ER) is associated with an increased risk for death from cardiac causes. Recent evidence supports ER's role as a modifier and/or predictor of risk in many cardiac conditions. OBJECTIVE: The purpose of this study was to determine the prevalence of ER among genotype-positive patients with long QT syndrome (LQTS) and evaluate its utility in predicting the risk of symptoms. METHODS: ER was defined as QRS slurring and/or notching associated with ≥1-mV QRS-ST junction (J-point) elevation in at least 2 contiguous leads, excluding the anterior precordial leads. The ECG with the most prominent ER was used for analysis. Major ER was defined as ≥ 2-mm J-point elevation. Symptoms of LQTS included cardiac syncope, documented polymorphic ventricular tachycardia (VT), and resuscitated cardiac arrest. RESULTS: One hundred thirteen patients (mean age 41 ± 19 years; 63 female) were reviewed, among whom 414 (mean 3.7 ± 1.5) ECGs were analyzed. Of these, 30 patients (27%) with a history of symptoms. Fifty patients (44%) had ER, and 19 patients (17%) had major ER. Patients with major ER were not different from patients without major ER with respect to age, sex, long QT type, longest QTc recorded, number of patients with QTc >500 ms, or use of beta-blockade. Univariate and independent predictors of symptom status included the presence of major ER, longest QTc recorded >500 ms, and female sex. CONCLUSION: ER ≥2 mm was the strongest independent predictor of symptom status related to LQTS, along with female sex and QTc >500 ms.

Dabigatran versus warfarin anticoagulation before and after catheter ablation for the treatment of atrial fibrillation.

BACKGROUND: Systemic thromboembolism and bleeding remain the two most common and serious complications of catheter ablation of atrial fibrillation. A variety of periprocedure anticoagulation strategies have been proposed to mitigate these risks. Although operators are now routinely administering dabigatran for anticoagulation in this setting, its relative safety and effectiveness compared to warfarin are unknown. METHODS AND RESULTS: A total of 202 patients received dabigatran as part of their periprocedural anticoagulation regimen at the time of initial or redo catheter ablation for symptomatic atrial fibrillation. A comparison group of 202 patients treated with warfarin was randomly selected from patients undergoing atrial fibrillation (AF) ablation during the same time period. AF types were paroxysmal in 223 patients, persistent in 158 patients, and longstanding persistent in 13 patients. Mean age was 60.0 ± 10.5 years, 55 % had a history of hypertension, and mean CHADS-VASc score was 1.7 ± 1.3. "Continuous" warfarin or dabigatran was administered in 80 and 32 % of patients, respectively. Time to first dose of dabigatran post-procedure was 12.2 ± 10.3 h. Two dabigatran and no warfarin-treated patients had systemic thromboembolism (p = NS); five dabigatran and three warfarin-treated patients had bleeding complications (p = NS, combined endpoint p = 0.116). One dabigatran patient had severe pericardial bleeding (3 L blood loss). CONCLUSIONS: In a retrospective pilot trial comparing the risks of systemic thromboembolism or bleeding complications in patients treated with warfarin or dabigatran anticoagulation, the outcomes were similar. A prospective trial is warranted.

Novel anti-arrhythmic medications in the treatment of atrial fibrillation.

Atrial fibrillation (AF) is a prevalent condition particularly amongst the elderly, which contributes to both morbidity and mortality. The burden of disease has lead to significant increases in health care utilization and cost in recent years. Treatment of Atrial fibrillation consists of either a rate or rhythm control strategy. Rhythm control is achieved using medical management and/or catheter ablation. In spite of major strides in catheter ablation, this procedure remains a second line treatment of AF. Anti-arrhythmic medications represent the main treatment modality for the maintenance of sinus rhythm. Amiodarone has been used for decades because of its efficacy and lack of pro-arrhythmia despite numerous extracardiac side effects. Novel agents such as Dronedarone were designed to emulate Amiodarone without the extra-cardiac side effects. Unfortunately recent trials have raised concerns for the safety of this medication in certain patients. Other agents such as Vernakalant and Ranolazine are in development that promise to be more atrial selective in their action, thereby potentially avoiding pro-arrhythmia and heart failure side effects. It remains to be seen however if one or more of these agents achieves the required high efficacy and safety threshold. This review summarizes the main anti-arrhythmic clinical trials, early phase trials involving novel agents and examines the conflicting data relating to Dronedarone.