clinicaltrials.gov Identifier: NCT00497146.

No abstract

Amiodarone, an iodinated benzofuran derivative, introduced in 1960's as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970's and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent. Because of its minimal negative inotropic activity and very low rate of pro-arrhythmia, it is considered safe in treating arrhythmias in patients with Coronary Artery Disease and Left ventricular systolic dysfunction. Despite these advantages, long term oral therapy with amiodarone is limited by side effect profile involving various organs like thyroid, lung, heart, liver, skin etc. Though the side effects can be decreased significantly by keeping the maintenance dose at 200 to 300 mg/day, patients on amiodarone should be followed closely. Amiodarone interacts with medications such as Warfarin, Digoxin, Macrolides, Floroquinolones etc., which share Cytochrome P450 metabolic pathway. Hence reducing their doses prior to starting amiodarone is recommended. Amiodarone, a category D drug, is contraindicated in pregnant and breast feeding women. This review discusses the pharmacokinetics of amiodarone, its evolving clinical indications, management of toxicity and drug interactions.

Background: In chronic kidney disease (CKD), left ventricular hypertrophy (LVH) is prevalent and is associated with increased cardiovascular morbidity and mortality. Vitamin D receptor (VDR) activation attenuates LVH progression in animal models. Methods: PRIMO is a multinational, randomized, double-blinded trial with oral paricalcitol in subjects with stages 3–4 CKD, mild-to-moderate LVH and an LV ejection fraction >50%. The primary endpoint is change in the left ventricular mass index (LVMI) compared with placebo after 48 weeks of treatment. The main secondary endpoints are changes in diastolic function parameters. In this paper, we report baseline characteristics from this study. Results: LVMI was 33.0 ± 7.5 g/m^2.7 for males and 30.8 ± 7.2 g/m^2.7 for females (p = 0.04). LVMI correlated with systolic blood pressure (r = 0.24), urine albumin creatinine ratio (r = 0.39), troponin T (r = 0.29), high-sensitivity C-reactive protein (r = 0.25) and plasma levels of B-type brain natriuretic peptide (r = 0.22); all p < 0.01. In multiple linear regression, each remained independently associated with LVMI. The early diastolic velocity of the lateral mitral annulus (E’) was 8.1 ± 2.4 cm/s. E’ was inversely correlated with age in univariate (r = –0.14, p = 0.04) and multivariable (p = 0.02) analysis. Conclusion: Among 227 multinational subjects with stages 3–4 CKD, baseline LVMI correlates with baseline blood pressure, urine albumin creatinine ratio and cardiac biomarkers, and baseline diastolic function correlates with age. This research was funded by Abbott Laboratories; ClinicalTrials.gov No. NCT00497146.