Thromboembolism and bleeding in patients with atrial fibrillation and liver disease - A nationwide register-based cohort study: Thromboembolism and bleeding in liver disease.

BACKGROUND: Balancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging. PURPOSE: To examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF. METHODS: Danish nationwide register-based cohort study of anticoagulant naive individuals with liver disease, incident atrial fibrillation/flutter, and a CHA2DS2-VASc-score≥1 (men) or ≥2 (women), alive 30 days after atrial fibrillation/flutter diagnosis. Thromboembolism was a composite of ischaemic stroke, transient ischaemic attack, or venous thromboembolism. Bleeding was a composite of gastrointestinal, intracerebral, or urogenital bleeding requiring hospitalisation, or epistaxis requiring emergency department visit or hospital admission. Cause-specific Cox-regression was used to estimate absolute risks and average risk ratios standardised to covariate distributions. Because of significant interactions with anticoagulants, results for thromboembolism were stratified for CHA2DS2-VASc-score, and results for bleeding were stratified for cirrhotic/non-cirrhotic liver disease. RESULTS: Four hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1-2 (2-3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22-2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45-0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status. CONCLUSION: Oral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease.

Serum Potassium and Mortality in High-Risk Patients: SPRINT.

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A Novel Model for Prediction of Thromboembolic and Cardiovascular Events in Patients Without Atrial Fibrillation.

Patients without atrial fibrillation (AF) constitute approximately 75% of patients suffering thromboembolism and major adverse cardiovascular events (MACE), but evidence supporting risk stratification in these patients is sparse. We aimed to develop a risk prediction model for identification of patients without AF at high risk of first-time thromboembolic events. We included 72,381 coronary angiography patients without AF and without previous ischemic stroke or transient ischemic attack. The cohort was randomly divided into a derivation cohort (80%, n = 57,680) and a validation cohort (20%, n = 14,701). The primary thromboembolic end point was a composite of ischemic stroke, transient ischemic attack, and systemic embolism. MACE was defined as a composite of cardiac death, myocardial infarction, and ischemic stroke. The final model was compared with 2 validated clinical risk models (CHADS2 and CHA2DS2-VASc). The risk prediction model assigned 1 point to heart failure, hypertension, diabetes mellitus, renal disease, age 65 to 74 years, active smoking, and multivessel obstructive coronary artery disease, and 2 points to age ≥75 years and peripheral artery disease. A C-index of 0.66 (95% CI 0.64 to 0.69) for prediction of the composite thromboembolic end point was found in the validation cohort, which was higher than for CHADS2 (C-index 0.63 [95% CI 0.60 to 0.67]; p < 0.001) and CHA2DS2-VASc (C-index 0.64 [95% CI 0.62 to 0.67]; p = 0.034). The model also predicted MACE (C-index 0.71 [95% CI 0.69 to 0.73]). In conclusion it is possible to identify patients without AF at high risk of first-time thromboembolic events and MACE by use of a simple clinical prediction model.

Predicting stroke in patients without atrial fibrillation.

BACKGROUND: Only few studies in selected cohorts have examined whether the CHA2 DS2 -VASc score can predict the risk of atrial fibrillation and thromboembolic events in patients without atrial fibrillation. MATERIALS AND METHODS: Patients with coronary angiography performed between 2004 and 2012 were grouped according to CHA2 DS2 -VASc score. We excluded patients with atrial fibrillation, anticoagulant therapy and follow-up <30 days. The endpoints were atrial fibrillation and a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. Event rates per 100 person-years were estimated for each CHA2 DS2 -VASc score (0, 1, 2, 3, 4, and >4). Incidence rate ratios were calculated using low-risk patients (CHA2 DS2 -VASc score 0 in males or 1 in females) as reference. RESULTS: In total, 78 233 patients were included with group sizes varying between 8299 (CHA2 DS2 -VASc >4) and 19 882 (CHA2 DS2 -VASc 2). An increasing CHA2 DS2 -VASc score was significantly associated with a future diagnosis of atrial fibrillation (P for trend <0.0001) and an incremental risk of ischaemic stroke, transient ischaemic attack, systemic embolism (P for trend <0.0001) and all-cause death (P for trend <0.0001). Patients with a CHA2 DS2 -VASc score of 3 had a rate of ischaemic stroke/transient ischaemic attack/systemic embolism of 1.30 per 100 person-years. CONCLUSIONS: Among patients undergoing coronary angiography, the CHA2 DS2 -VASc score predicted a future diagnosis of atrial fibrillation and the composite risk of ischaemic stroke, transient ischaemic attack or systemic embolism in patients without atrial fibrillation. A CHA2 DS2 -VASc score of 3 was associated with a risk that would justify prophylactic oral anticoagulation treatment in a patient with atrial fibrillation.

Comparison of Frequency of Ischemic Stroke in Patients With Versus Without Coronary Heart Disease and Without Atrial Fibrillation.

Recent trials of antithrombotic therapy in patients with coronary artery disease (CAD) have demonstrated substantial reductions in ischemic stroke. Our aim was to examine ischemic stroke risk in patients with CAD and to identify those at highest risk. We examined ischemic stroke risk in patients without atrial fibrillation who underwent coronary angiography between 2004 and 2012. Patients were stratified according to presence or absence of CAD and further stratified by extent of CAD (0 vessel disease [VD], 1 VD, 2 VD, 3 VD, and diffuse VD). End points were composites of ischemic stroke, transient ischemic attack (TIA), and systemic embolism, as well as major adverse cardiovascular and cerebrovascular events (MACCE) defined as cardiac death, myocardial infarction, plus ischemic stroke, TIA, and systemic embolism. Adjusted incidence rate ratios (IRRs) were estimated. A total of 68,829 patients were included, 25,032 had 0 VD, 4,736 had diffuse VD, 18,471 had 1 VD, 10,588 had 2 VD, and 10,002 had 3 VD. Median follow-up was 4.0 years. CAD extent was associated with an increased risk of stroke, TIA, and systemic embolism (1 VD: adjusted IRR 1.02, 95% confidence interval [CI] 0.90 to 1.16; diffuse VD: adjusted IRR 1.22, 95% CI 1.02 to 1.47; 2 VD: adjusted IRR 1.28, 95% CI 1.12 to 1.45; 3 VD: adjusted IRR 1.37, 95% CI 1.20 to 1.55) compared with patients with 0 VD. Presence and extent of CAD were also associated with MACCE. In conclusion, CAD is associated with an increased risk of stroke, TIA, and systemic embolism and MACCE in patients without atrial fibrillation, and patients with coronary multi-VD are at highest risk and may be candidates for treatment strategies aiming at reducing ischemic stroke incidence.

Should the Presence or Extent of Coronary Artery Disease be Quantified in the CHA2DS2-VASc Score in Atrial Fibrillation? A Report from the Western Denmark Heart Registry.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk of ischaemic stroke. The risk can be predicted by the CHA2DS2-VASc score, in which the vascular component refers to previous myocardial infarction, peripheral artery disease and aortic plaque, whereas coronary artery disease (CAD) is not included. OBJECTIVES: This article explores whether CAD per se or extent provides independent prognostic information of future stroke among patients with AF. MATERIALS AND METHODS: Consecutive patients with AF and coronary angiography performed between 2004 and 2012 were included. The endpoint was a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. The risk of ischaemic events was estimated according to the presence and extent of CAD. Incidence rate ratios (IRR) were calculated in reference to patients without CAD and adjusted for parameters included in the CHA2DS2-VASc score and treatment with anti-platelet agents and/or oral anticoagulants. RESULTS: Of 96,430 patients undergoing coronary angiography, 12,690 had AF. Among patients with AF, 7,533 (59.4%) had CAD. Mean follow-up was 3 years. While presence of CAD was an independent risk factor for the composite endpoint (adjusted IRR, 1.25; 1.06-1.47), extent of CAD defined as 1-, 2-, 3- or diffuse vessel disease did not add additional independent risk information. CONCLUSION: Presence, but not extent, of CAD was an independent risk factor of the composite thromboembolic endpoint beyond the components already included in the CHA2DS2-VASc score. Consequently, we suggest that significant angiographically proven CAD should be included in the vascular disease criterion in the CHA2DS2-VASc score.