Predictors and prognostic implications of incident heart failure following the first diagnosis of atrial fibrillation in patients with structurally normal hearts: the Belgrade Atrial Fibrillation Study.

AIM: Atrial fibrillation (AF) commonly co-exists with heart failure (HF). The risk factors for and prognostic implications of incident HF development in patients with first-diagnosed AF and structurally normal hearts are poorly defined. In a cohort of patients with first-diagnosed AF and structurally normal hearts on baseline echocardiography, we investigated baseline risk factors for the development of incident HF and tested the hypothesis that incident HF was an independent predictor of adverse outcomes during a mean 10-year follow-up period. METHODS AND RESULTS: This was a registry-based, observational cohort study of 842 patients initially diagnosed between 1992 and 2007 (mean age 51.6 ± 12.4 years), whereby 83 (9.9%) developed HF. The linearized rate of incident HF was 0.97% [95% confidence interval (CI) 0.78-1.19%] per 100 patient-years. Baseline history of hypertension, diabetes mellitus, dilated left atrium, and low-normal LVEF (50-54%) were multivariable predictors of subsequent HF (all P < 0.05). HF development was significantly associated with increased number of hospitalizations, AF progression, any stroke/peripheral thrombo-embolism, ischaemic stroke, cardiovascular death, and all-cause mortality (all P < 0.001). Kaplan-Meier 10-year estimates of survival free of the composite endpoint of AF progression, thrombo-embolism, and mortality were significantly worse for AF patients with incident HF compared with those without HF (68.8%; 95% CI 64.7-72.9 vs. 25.9% 95% CI 15.7-36.1, P < 0.001). CONCLUSION: Underlying co-morbidities or subtle alterations such as mild left atrial dilatation or low-normal LVEF in the absence of overt underlying heart disease are baseline independent risk factors for incident HF during a long-term follow-up. Incident HF was an independent predictor of adverse outcomes in patients initially diagnosed with first-diagnosed AF and structurally normal hearts. These findings could facilitate the identification of AF patients at increased risk for adverse outcomes within the cohort perceived as being at 'low risk' given a structurally normal heart on echocardiography.

Novel oral anticoagulants for stroke prevention in atrial fibrillation: focus on apixaban.

Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality, with a similar reduction in the rate of ischemic stroke and better tolerability. When compared with aspirin in the AVERROES trial, apixaban was associated with more effective reduction of stroke, a similar risk of major bleeding, and better tolerability. In this review article, the authors summarize the current knowledge on novel oral anticoagulants and discuss the clinical aspects of their use for stroke prevention in AF, with particular emphasis on apixaban.

Reliable identification of "truly low" thromboembolic risk in patients initially diagnosed with "lone" atrial fibrillation: the Belgrade atrial fibrillation study.

BACKGROUND: The CHA(2)DS(2)-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack [TIA], Vascular disease, Age 65-74 years, and Sex category [female gender]) schema recently has been introduced to complement the CHADS(2) (Congestive heart failure, Hypertension, Age >75 years, Diabetes mellitus, and previous stroke or TIA) score and improve the identification of atrial fibrillation (AF) patients at "truly low risk" for thromboembolism. We tested the predictive ability of the CHA(2)DS(2)-VASc, CHADS(2), and van Walraven risk stratification schemes in a cohort of "lone" AF patients with a 12-year follow-up. METHODS AND RESULTS: We conducted a registry-based, observational cohort study of 345 patients initially diagnosed with "lone" AF between 1992 and 2007. At baseline, all patients had the CHADS(2) and van Walraven scores of 0, and 262 (75.9%) had a CHA(2)DS(2)-VASc score of 0. During follow-up (or within a year prior to stroke), 228 (66.1%), 234 (67.8%), and 150 patients (43.5%) retained the CHADS(2), van Walraven, and CHA(2)DS(2)-VASc scores of 0, respectively. The overall rate of ischemic stroke was 0.19 (95% CI: 0.18-0.20) per 100 patient years. In the multivariable analysis, only the CHA(2)DS(2)-VASc score of 0 was significantly related to the absence of stroke (odds ratio 5.1, 95% CI: 1.5-16.8, P=0.008). Only the CHA(2)DS(2)-VASc score had a significant prediction ability (c-statistic 0.72 [0.61-0.84], P=0.031). CONCLUSIONS: The CHA(2)DS(2)-VASc score reliably identified the "lone" AF patients who were at "truly low risk" for thromboembolism, and was the only tested risk stratification scheme with a significant predictive ability for thromboembolism among lone AF patients.