Carpio, Freddy Del

Introduction: The efficacy and safety of novel oral anticoagulants (NOACs) has not been assessed in subjects with renal impairment. Methods: We performed a meta-analysis of RCTs comparing NOACs with warfarin in patients with atrial fibrillation (AF), in relation to renal function estimated by glomerular filtration rate (GFR): normal (GFR>80 ml/min/1.73m2), mild (50-80 mL/min/1.73m2), and moderate (<50 mL/min/1.73m2) impairment. MEDLINE, Embase, Web of Science and the Cochrane Library were searched to identify articles published up to the third week of January 2015. Data were supplemented with FDA data. Data on stroke or systemic embolism (S/SE) and major bleeding according to renal function were collected and extracted. We estimated the pooled relative risk (RR) of S/SE and major bleeding, for NOACs compared to warfarin. Results: We retrieved four randomized clinical trials (each randomizing dabigatran, rivaroxaban, apixaban, or endoxaban versus warfarin) enrolling a total of 58338 subjects, 29123 randomized to NOACs and 29123 randomized to warfarin; 21132 had normal renal function, 13126 had mild and 11027 had moderate renal impairment. In subjects with moderate renal impairment, compared to warfarin, NOACs reduced the risk of S/SE (RR 0.8; 95% CI 0.68-0.94) and major bleeding (RR 0.80; 95% CI 0.71-0.91). In subjects with mild renal impairment NOACs were associated with a reduced risk of S/SE (RR 0.75; 95% CI 0.66-0.85) and major bleeding (RR 0.87; 95% CI 0.79-0.95). In subjects with normal renal function no difference in the risk of S/SE was observed, while the risk of major bleeding was slightly less for subjects taking NOACs (RR 0.87; 95% CI 0.76-0.99). The test for interaction among groups of renal function was borderline significant for S/SE, but not for major bleeding. Conclusions: The use of NOACs was associated with a reduced risk of S/SE in subjects with mild or moderate renal impairment; while the risk of bleeding was reduced by NOACs compared to warfarin.

Introduction: Clinical predictive value of transient prolonged ventricular conduction and repolarization during right ventricular (RV) pacing have not been studied. Hypothesis: Ventricular conduction and repolarization prolongation during RV pacing predict risk of arrhythmic and mortality events. Methods: Electrophysiology studies in 501 patients with cardiomyopathy (CM) were reviewed. Duration changes of QRS and QT interval during pacing from the RV apex were measured. Subjects were followed up for a mean of 3.2 years for arrhythmic events and total mortality. Results: Participants had a mean age 65 yrs, 80% male, 74% funcional class II or III, and a mean EF of 33.1%. A paced QRS duration > 190 ms was associated with more severe CM and in multi-variable analysis it was associated with a 3.5 times higher risk of ventricular arrhythmias or appropriate defibrillator therapy (HR 3.5, 95% CI 2.3-5.4, p<0.01) and 2.6 times higher risk of total mortality or arrhythmic events (HR 2.6, 95% CI 2.3-3.4, p<0.01) compared to a paced QRS duration <190 ms, independent of baseline EF or baseline QRS duration, and after adjustment for electrophysiology study results, baseline functional class, type of cardiomyopathy and other relevant clinical factors. Similarly a QTc interval during RV pacing > 620 ms was associated with a 2.7 times higher risk of arrhythmic events compared to a QTc interval during RV pacing < 620 ms. Conclusions: Prolongation of ventricular conduction (QRS > 190 ms) and repolarization (QTc > 620 ms) observed during RV pacing in subjects with CM are associated with higher risk of arrhythmic events, defibrillator therapies and all-cause mortality.