Differential efficacy and safety of oral anticoagulation in atrial fibrillation patients with or without comorbid vascular disease: insights from the GARFIELD-AF registry
Authors: Verheugt F W A , Fox K A A , Virdone S , Gersh B J , Haas S , Pieper K , Kayani G , Camm A J , Parkhomenko A , Kakkar A K 
Published: October 2022

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).