Camm, A. John

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).

Abstract Background Many patients with atrial fibrillation (AF) have comorbid vascular disease. The effects of oral anticoagulation (OAC) in AF patients with vascular disease, however, have not been widely studied. Purpose To investigate the impact of OAC in AF patients with (Vasc) or without (nVasc) concomitant vascular disease. Methods GARFIELD-AF is the largest multinational, prospective AF registry. The study comprised 51,574 GARFIELD-AF patients with newly diagnosed AF, 13,365 Vasc and 38,209 nVasc patients. All patients who reported coronary artery disease, aortic or peripheral artery disease, acute coronary syndromes, myocardial infarction, stenting, or coronary artery bypass graft were classified as having vascular disease. Adjusted hazard ratios were obtained via Cox proportional-hazards models to quantify the association of vascular disease with selected endpoints. Comparative effectiveness analyses were restricted to patients enrolled from April 2013-September 2016 (when NOACs became widely available) and who were eligible for anticoagulation (CHA2DS2-VASc ≥2 excl. gender). To evaluate the safety and efficacy of different anticoagulation strategies in Vasc and nVasc patients, propensity score using an overlap weighting scheme was applied. Weights were applied to Cox proportional-hazards models to estimate the effects of OAC vs No OAC and NOAC vs VKA. Results Vasc patients were older (median (Q1; Q3): 72.0 (65.0; 79.0) vs 70.0 (62.0; 78.0) and more often male (62.0 vs 53.6%). Vasc patients had a higher rate of comorbidities including heart failure, hypertension, and diabetes. Vasc patients received less OAC (62.8 vs 68.3%). NOACs were less common compared with nVasc patients (23.8% vs 28.7%) but a similar proportion of VKAs was observed in both (39.0% vs 39.6%). Antiplatelet monotherapy was more common in Vasc (31%) than nVasc (18%) patients. At 2-years, Vasc was associated with a higher risk of all-cause (HR [95% CI]: 1.30 [1.16–1.47]) and cardiovascular mortality (1.59 [1.28–1.97]). OACs significantly lowered the risk of all-cause mortality and stroke in nVasc patients (0.72 [0.63–0.82] and 0.64 [0.49–0.84], respectively), but not in nVasc patients. OACs led to a numerical increase in major bleeding in Vasc patients (1.32 [0.90–1.93]) and a significant increase in major bleeding in nVasc patients (1.40 [1.03–1.90]) (Figure 1). Compared with VKAs, NOACs did not significantly improve the risk of outcomes in nVasc patients. In Vasc patients however, NOACs significantly lowered the risk of all-cause mortality (0.74 [0.61–0.90]) and major bleeding (0.45 [0.29–0.70]) compared with VKAs (Figure 2). Conclusion AF patients with vascular disease have worse long-term outcomes than those without. They receive less often OAC, specifically NOAC, and more antiplatelet agents. The beneficial effects of NOAC over VKA are much more pronounced in patients with than in those without vascular disease. 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).