Long-term cardiovascular outcomes in patients with atrial fibrillation and atherothrombosis in the REACH Registry

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Abstract

Background

Patients with atrial fibrillation (AF) are at increased risk of thromboembolic events. The long-term prognostic implications of AF in patients with atherothrombosis are unknown.

Methods

We compared 4-year CV outcomes in patients with and without a history of AF recorded at their baseline visit in the REACH Registry, an international, prospective cohort of patients with established atherosclerotic arterial disease (CAD, CVD, PAD) or at least 3 risk factors (RFO).

Results

AF status and 4 year follow-up data were available on 44,518 patients. The prevalence of AF at baseline was 10.3% (n = 4582). Overall, patients with AF had approximately a 2-fold increase in the composite of CV death, MI, or stroke compared with patients without AF after adjustment for age, gender, prior ischemic event, vascular disease, congestive heart failure, diabetes, smoking, body mass index, region, aspirin and statin use (18.9% vs. 9.4%, p < 0.0001). This increased risk was observed both in patients with established atherothrombosis (CAD: 15.5% vs. 8.0%, p = 0.0001; CVD: 23.6% vs. 13.6%, p < 0.0001; PAD: 24.3% vs. 13.5%, p = 0.089) and those with multiple risk factors (RFO: 12.1% vs. 5.9%, p = 0.017). Only 52% of patients with a history of AF at baseline were receiving anticoagulation at 4 years.

Conclusions

Patients with a history of both AF and atherothrombosis have particularly high long-term CV risk. Despite this increased risk, almost half of all patients with AF do not receive guideline recommended anticoagulation, highlighting an important public health priority.

Introduction

It has been estimated that 2.2 million people in the United States, 4.5 million people in the European Union [1] and 8 million people in China [2] suffer from atrial fibrillation (AF) with a prevalence that is estimated to at least double within the next 50 years [3]. Thromboembolism, primarily ischemic stroke, is the most feared and devastating complication of AF [4], [5], [6], [7], [8], occurs in approximately 5% of patients per year without anticoagulation (a 2 to 7 fold increase in risk) [9], [10], [11].

Conditions associated with AF are also markers of global cardiovascular risk, therefore, it is not surprising that AF is common in patients with stable atherosclerosis and those who have suffered an ischemic event [12]. Coronary artery disease is present in ≥ 20% of the AF population [13], [14] and AF complicating acute coronary syndromes (ACS) is associated with a markedly increased in-hospital and long-term mortality [15]. The presence of atherosclerotic vascular disease may also contribute to stroke risk. In AF patients, an increased risk of stroke and thromboembolism is seen in patients with a previous myocardial infarction (MI) and/or peripheral artery disease [16], [17], [18]. In fact, in many patients it is postulated that AF is a marker or surrogate of increased vascular stiffness causing diastolic dysfunction, atrial volume overload and increased vulnerability to AF [19], [20], [21].

Despite the extensive overlap between AF and atherosclerosis and the possibility that patients with both conditions represent a very high risk group with a synergistic increase in both ischemic and thromboembolic events, there are very few large, well-characterized studies that provide long-term outcomes. The international Reduction of Atherothrombosis for Continued Health (REACH) Registry provides an opportunity to examine the impact of AF in a large, international population of “real world” patients with various manifestations of atherosclerosis, spanning from asymptomatic adults with risk factors, to patients with stable atherosclerosis, to those with prior ischemic events [22], [23], [24], [25], [26]. One-year data from the REACH Registry demonstrate an increased risk of fatal and non-fatal outcomes in patients with AF [27]. The present analysis seeks to provide long-term data regarding the prognosis and utilization rates of evidence-based antithrombotic therapies in this vulnerable population.

Section snippets

Methods

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

Results

Among the 68,236 patients enrolled in the REACH registry, 44,518 were eligible for inclusion in this analysis (4 year outcomes data and AF present or absent confirmed at baseline). The prevalence of baseline AF in the entire cohort was 10.3% (n = 4582) and was consistent in the main symptomatic subgroups: CAD 12.0%, CVD 13.2%, PAD 10.3%, and lower in the RFO group: 6.2%.

The baseline characteristics of patients with and without AF are shown in Table 1. As expected, patients with AF were older (72.6 

Discussion

This analysis of a large, international registry demonstrates that AF is a frequent companion to atherosclerosis and the presence of both is a powerful predictor of adverse cardiovascular events over a 4-year follow-up period. Despite a markedly increased risk, this vulnerable population is routinely undertreated with anticoagulant therapy.

This study supports that the prevalence of AF is higher in patients with atherothrombosis compared to the general population (age matched 5–7%) [3], [30],

Conclusions

In conclusion, AF is prevalent in patients across the spectrum of atherosclerosis and the presence of both conditions imparts a substantial long-term risk of cardiovascular events. This large, international study underscores that these vulnerable, high-risk patients often do not receive guideline recommended care likely due to the complexity of their management and the lack of data informing clinicians on the optimal treatment approach. Although a new era of anticoagulation therapy is on the

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    1

    A complete list of the REACH Registry Investigators appears in JAMA. 2006;295:180-189.

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