Faculty Bibliography

Warfarin prevents stroke and prolongs survival in patients with atrial fibrillation and flutter (AF, collectively) but can cause hemorrhage. The time in international normalized ratio (INR) therapeutic range (TTR) mediates stroke reduction and bleeding risk. This study sought to determine the relation between baseline stroke, bleeding risk, and TTR. Using data from The Retrospective Evaluation and Assessment of Therapies in Atrial Fibrillation (TREAT-AF) retrospective cohort study, national Veterans Health Administration records were used to identify patients with newly diagnosed AF from 2003 to 2012 and subsequent initiation of warfarin. Baseline stroke and bleeding risk was determined by calculating CHA₂DS₂-VASc and HAS-BLED scores, respectively. Main outcomes were first-year and long-term TTR and INR monitoring rate. In 167,190 patients, the proportion of patients with TTR (>65%) decreased across increasing strata of CHA₂DS₂-VASc and HAS-BLED. After covariate adjustment, odds of achieving TTR >65% were significantly associated with high CHA₂DS₂-VASc or HAS-BLED score. INR monitoring rate was similar across risk strata. In conclusion, increased baseline stroke and bleeding risk is associated with poor INR control, despite similar rates of INR monitoring. These findings may paradoxically limit warfarin's efficacy and safety in high-risk patients and may explain observed increased bleeding and stroke rates in this cohort.

Almost 800,000 new or recurrent strokes occur every year. Atrial fibrillation, the most common cardiac arrhythmia, is a major risk factor for stroke, accounting for 15-20% of ischemic strokes. Apixaban is a direct inhibitor of Factor Xa that was approved in December 2012 by the US Food and Drug Administration (FDA) for the prevention of stroke in patients with non-valvular atrial fibrillation. It is part of a family of novel oral anticoagulants (NOACs) which has advantage over warfarin of less dosing variability, rapid onset of action and no INR monitoring required. Apixaban showed superiority to warfarin in both primary efficacy and primary safety outcomes by simultaneously showing both significantly lower rates of strokes and systemic embolism and a reduced risk of major clinical bleeding in clinical trials. Warfarin remains the anticoagulant of choice for patients with prosthetic heart valves and significant mitral stenosis. There are currently no head-to-head studies that directly compare the different NOACs with one another, but it is expected that there will be more trials in the future that will explore this comparison. Dabigatran is the only NOAC with an FDA approved reversal agent. However, a reversal agent for apixaban is being developed and was successful in recent clinical trials. This review summarizes the clinical trial data on apixaban for atrial fibrillation, compares apixaban to other NOACs and discusses apixaban use in clinical practice.

Convergent atrial fibrillation ablation involves extensive epicardial as well as endocardial ablation of the left atrium. We examined whether it changes the morphology of the surface P wave. We reviewed electrocardiograms of 29 patients who underwent convergent ablation for atrial fibrillation. In leads V1, II and III, we measured P wave duration, area and amplitude before ablation, and at 1, 3 and 6 months from ablation. After ablation, there were no significant changes in P wave amplitude, area, or duration in leads II and III. There was a significant reduction in the area of the terminal negative deflection of the P wave in V1 from 0.38 mm(2) to 0.13 mm(2) (p = 0.03). There is also an acute increase in the amplitude and duration of the positive component of the P wave in V1 followed by a reduction in both by 6 months. Before ablation, 62.5% of the patients had biphasic P waves in V1. In 6 months, only 39.2% of them had biphasic P waves. Hybrid ablation causes a reduction of the terminal negative deflection of the P wave in V1 as well as temporal changes in the duration and amplitude of the positive component of the P wave in V1. This likely reflects the reduced electrical contribution of the posterior left atrium after ablation as well as anatomical and autonomic remodeling. Recognition of this altered sinus P wave morphology is useful in the diagnosis of atrial arrhythmias in this patient population.

The influence of race on quality of anticoagulation control is not well described. We examined the association between race, international normalized ratio (INR) monitoring intensity, and INR control in warfarin-treated patients with atrial fibrillation (AF). Using data from the Veterans Health Administration (VHA), we performed a retrospective cohort study of 184,161 patients with a new diagnosis of AF/flutter from 2004 to 2012 who received any VHA prescription within 90 days of diagnosis. The primary predictor was race, ascertained from multiple VHA and linked Medicare demographic files. The primary outcome was first-year and long-term time in therapeutic range (TTR) of INR 2.0 to 3.0. Secondary outcomes were INR monitoring intensity and warfarin persistence. Of the 116,021 patients who received warfarin in the cohort, INR monitoring intensity was similar across racial groups. However, TTR was lowest in blacks and highest in whites (first year 0.49 ± 0.23 vs 0.57 ± 0.21, p <0.001; long term 0.52 ± 0.20 vs 0.59 ± 0.18, p <0.001); 64% of whites and 49% of blacks had long-term TTR >55% (p <0.001). After adjusting for site and patient-level covariates, black race was associated with lower first-year and long-term TTRs (4.2% and 4.1% below the conditional mean, relative to whites; p <0.0001 for both). One-year warfarin persistence was slightly lower in blacks compared to whites (58% vs 60%, p <0.0001). In conclusion, in patients with AF anticoagulated with warfarin, differences in INR control are most evident among blacks, underscoring the need to determine if other types of intensive management or warfarin alternatives may be necessary to improve anticoagulation among vulnerable AF populations.