Janský, Petr

Abstract Background Atrial fibrillation is associated with considerable morbidity and mortality. Real-world reports on the effect of early rhythm control on patient outcomes in patient with recent onset atrial fibrillation are limited. Purpose To assess the effect of early rhythm versus rate control on clinical outcomes in patients with newly diagnosed non-valvular atrial fibrillation. Method The Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) is a non-interventional registry of adult (≥18 years) patients with newly diagnosed atrial fibrillation (≤ six weeks' duration) and at least one investigator determined risk factor for stroke. Patients were enrolled in 1317 participating sites in 35 countries between March 2010 and August 2016. Patients with permanent atrial fibrillation were excluded. Stratification to rhythm or rate control was based on treatment strategy initiated at baseline (≤48 days post enrolment). Rhythm control was defined as investigator reported initiation of rhythm control (antiarrhythmic drug(s), cardioversion, or ablation – alone or in combination with rate modifiers). Rate control was defined as investigator reported initiation of rate control and absence of rhythm control therapy. Overlap propensity weighting and Cox proportional-hazards models were used to evaluate effect on outcomes. Results Of 45,382 included patients, 23,858 (52.6%) received rhythm control and 21,524 (47.4%) rate control. Rates of rhythm control were similar throughout the study time period (52.7% in 2010/2011, 54.2% in 2015/2016). Patients in the rhythm control group were younger (median age (Q1; Q3) 68.0 (60.0; 76.0) versus 73.0 (65.0; 79.0)), had lower rates of prior stroke/transitory ischemic attack/systemic embolism (9.4% vs 13.0%), and a lower median GARFIELD death score (4.0 (2.3; 7.5) versus 5.1 (2.8; 9.2)). Median CHA2DS2-VASc Scores were 3.0 (2.0; 4.0) in both groups. Rate of anticoagulation treatment was similar in the rhythm and rate control group (66.0% versus 65.5%). After propensity score overlap weighting, patients of the two groups were well balanced on all observed characteristics. Event rates per 100 person-years (95% confidence interval [CI]) over two years follow-up in the rhythm and rate control group were 2.94 (2.78–3.10) versus 4.43 (4.22–4.64) for mortality, 0.84 (0.75–0.92) versus 1.16 (1.05–1.27) for non-haemorrhagic stroke/systemic embolism and 0.84 (0.76–0.93) versus 1.16 (1.06–1.27) for major bleeding. Adjusted hazard ratios (95% CI) for the same time period were 0.85 (0.79–0.92), 0.84 (0.72–0.97) and 0.9 (0.78–1.04). Conclusion In this large, internation registry, a rhythm control strategy was initiated at baseline in about half of the patients with newly diagnosed non-valvular atrial fibrillation. After adjustment for confounding factors, a significantly lower risk of all-cause mortality and non-haemorrhagic stroke/systemic embolism were observed for patients that received an early rhythm control strategy. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by the Thrombosis Research Institute (London, UK).

Objective To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. Methods There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model. Results Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory. Conclusions In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS. Clinical trial registration ARISTOTLE clinical trial number NCT00412984.