Markus Lucerna

Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients With Atrial Fibrillation: A Sub‐Analysis From the PREFER in AF ( PRE vention o F Thromboembolic Events– E uropean R egistry in A trial F ibrillation)

Background Increasing age predisposes to both thromboembolic and bleeding events in patients with atrial fibrillation; therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. We investigated 1‐year outcome with different antithrombotic approaches in very elderly atrial fibrillation patients (age ≥85 years) compared with younger patients. Methods and Results We accessed individual patients’ data from the prospective PREFER in AF (PREvention oF thromboembolic events‐European Registry in Atrial Fibrillation), compared outcomes with and without oral anticoagulation (OAC), and estimated weighed net clinical benefit in different age groups. A total of 6412 patients, 505 of whom were aged ≥85 years, were analyzed. In patients aged <85 years, the incidence of thromboembolic events was 2.8%/year without OAC versus 2.3%/year with OAC (0.5% absolute reduction); in patients aged ≥85 years, it was 6.3%/year versus 4.3%/year (2% absolute reduction). In very elderly patients, the risk of major bleeding was higher than in younger patients, but similar in patients on OAC and in those on antiplatelet therapy or without antithrombotic treatment (4.0%/year versus 4.2%/year; P=0.77). OAC was overall associated with weighted net clinical benefit, assigning weights to nonfatal events according to their prognostic implication for subsequent death (−2.19%; CI, −4.23%, −0.15%; P=0.036). We found a significant gradient of this benefit as a function of age, with the oldest patients deriving the highest benefit. Conclusions Because the risk of stroke increases with age more than the risk of bleeding, the absolute benefit of OAC is highest in very elderly patients, where it, by far, outweighs the risk of bleeding, with the greatest net clinical benefit in such patients.

Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation

Objectives Our objective was to examine gender differences in clinical presentation, management and prognosis of atrial fibrillation (AF) in a contemporary cohort. Methods In 6412 patients, 39.7% women, of the PREvention oF thromboembolic events – European Registry in Atrial Fibrillation, we examined gender differences in symptoms, risk factors, therapies and 1-year incidence of adverse outcomes. Results Men with AF were on average younger than women (mean±SD: 70.1±10.7 vs 74.1±9.7 years, p<0.0001). Women more frequently had at least one AF-related symptom at least occasionally compared with men (95.4% in women, 89.8% in men, p<0.0001). Prescription of oral anticoagulation was similar, with an increase of non-vitamin K antagonist oral anticoagulants from 5.9% to 12.6% in women and from 6.2% to 12.6% in men, p<0.0001 for both. Men were more frequently treated with electrical cardioversion and ablation (20.6% and 6.3%, respectively) than women (14.9% and 3.3%, respectively), p<0.0001. Women had 65% (OR: 0.35; 95% CI (0.22 to 0.56)) lower age-adjusted and country-adjusted odds of coronary revascularisation, 40% (OR: 0.60; (0.38 to 0.93)) lower odds of acute coronary syndrome and 20% (OR: 0.80; (0.68 to 0.96)) lower odds of heart failure at 1 year. There were no statistically significant gender differences in 1-year stroke/transient ischaemic attack/arterial thromboembolism and major bleeding events. Conclusion In a ‘real-world’ European AF registry, women were more symptomatic but less likely to receive invasive rhythm control therapy such as electrical cardioversion or ablation. Further study is needed to confirm that these differences do not disadvantage women with AF.

Symptom Burden of Atrial Fibrillation and Its Relation to Interventions and Outcome in Europe

Background Little is known about the association of atrial fibrillation symptom burden with quality of life and outcomes. Methods and Results In the Prevention of Thromboembolic Events–European Registry in Atrial Fibrillation (n=6196 patients with atrial fibrillation; mean±SD age, 71.8±10.4 years; 39.7% women), we assessed European Heart Rhythm Association score symptoms and calculated correlations with the standardized health status questionnaire (EQ‐5D‐5L). Patients were followed up for atrial fibrillation therapies and outcomes (stroke/transient ischemic attack/arterial thromboembolism, coronary events, heart failure, and major bleeding) over 1 year. Most individuals (92%) experienced symptoms. Correlations with health status and quality of life were modest. In multivariable‐adjusted regression models, the dichotomized European Heart Rhythm Association score (intermediate/frequent versus never/occasional symptoms) was associated with cardioversions (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.01–1.45) and catheter ablation (OR, 1.97; 95% CI, 1.44–2.69), and inversely related with heart rate control (OR, 0.80; 95% CI, 0.70–0.92) and heart failure incidence (OR, 1.65; 95% CI, 1.16–2.34). Anxiety was inversely related with stroke/transient ischemic attack/arterial thromboembolism (OR, 0.55; 95% CI, 0.32–0.93), whereas chest pain related positively with coronary events (OR, 2.45; 95% CI, 1.42–4.22). Fatigue (OR, 1.84; 95% CI, 1.30–2.60), dyspnea (OR, 2.33; 95% CI, 1.63–3.33), and anxiety (OR, 1.72; 95% CI, 1.16–2.55) were associated with heart failure incidence. Palpitations were positively associated with cardioversion (OR, 1.32; 95% CI, 1.08–1.61) and ablation therapy (OR, 2.02; 95% CI, 1.48–2.76). Conclusions A higher symptom burden, in particular palpitations, predicted interventions to restore sinus rhythm. The score itself had limited predictive value, but its individual components were related to different and specific clinical events, and may thus be helpful to target patient management.

Heart failure subtypes and thromboembolic risk in patients with atrial fibrillation: The PREFER in AF - HF substudy

BACKGROUND AND OBJECTIVES To assess thromboembolic and bleeding risks in patients with heart failure (HF) and atrial fibrillation (AF) according to HF type. METHODS We analyzed 6170 AF patients from the Prevention of thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF), and categorized patients into: HF with reduced left-ventricular ejection fraction (HFrEF; LVEF < 40%); mid-range EF (HFmrEF; LVEF: 40-49%); lower preserved EF (HFLpEF; LVEF: 50-60%), higher preserved EF (HFHpEF; LVEF > 60%), and no HF. Outcomes were ischemic stroke, major adverse cardiovascular and cerebral events (MACCE) and major bleeding occurring within 1-year. RESULTS The annual incidence of stroke was linearly and inversely related to LVEF, increasing by 0.054% per each 1% of LVEF decrease (95% CI: 0.013%-0.096%; p = 0.031). Patients with HFHpEF had the highest CHA2DS2-VASc score, but significantly lower stroke incidence than other HF groups (0.65%, compared to HFLpEF 1.30%; HFmrEF 1.71%; HFrEF 1.75%; trend p = 0.014). The incidence of MACCE was also lower in HFHpEF (2.0%) compared to other HF groups (range: 3.8-4.4%; p = 0.001). Age, HF type, and NYHA class were independent predictors of thromboembolic events. Conversely, major bleeding did not significantly differ between groups (p = 0.168). CONCLUSION Our study in predominantly anticoagulated patients with AF shows that, reduction in LVEF is associated with higher thromboembolic, but not higher bleeding risk. HFHpEF is a distinct and puzzling group, featuring the highest CHA2DS2-VASc score but the lowest residual risk of thromboembolic events, which warrants further investigation.

Outcomes of anticoagulated patients with atrial fibrillation treated with or without antiplatelet therapy - A pooled analysis from the PREFER in AF and PREFER in AF PROLONGATON registries

BACKGROUND Evidence on whether antiPLT added to OACs is of advantage in atrial fibrillation (AF) patients with concomitant stable coronary artery disease (CAD) is limited. We evaluated clinical outcomes with oral anticoagulant (OAC) monotherapy vs antiplatelet therapy (antiPLT) plus OAC in patients with AF and stable CAD. METHODS Data on 1058 AF patients on OACs and history (>1 year) of myocardial infarction or coronary stenting were pooled from the PREFER-in-AF and PREFER-in-AF PROLONGATION registries. We primarily compared the 1-year incidence of a net composite endpoint (primary endpoint), including acute coronary syndrome and major bleeding, with or without antiPLT. RESULTS The incidence of the primary net composite endpoint was significantly higher in patients receiving OACs + antiPLT (N = 348) vs OACs alone (N = 710): 7.9 vs 4.2 per 100 patients/year; adjusted OR [95% CI] 1.84 [1.01-3.37]; p = 0.048. Among the components of the primary endpoint, the greatest relative difference was found for major bleeding (OR [95% CI] 2.28 [95% CI 1.00-5.19]), and especially life-threatening or non-gastrointestinal bleeding. The net clinical outcome with OACs + antiPLT was poorer irrespective of the type of CAD (previous infarction or coronary stenting), the type of stent (bare metal or drug-eluting) or the type of OAC (vitamin K antagonist or non-vitamin K antagonist OAC). CONCLUSIONS Among patients with AF and stable CAD >1-year after the index event, the addition of antiPLT to OAC does not apparently provide added protection against coronary events, but increases major bleeding. OAC monotherapy should thus be considered the antithrombotic therapy of choice for such patients.

Atrial fibrillation patterns are associated with arrhythmia progression and clinical outcomes

Objectives Determinants of atrial fibrillation (AF) patterns and of progression of earlier forms to permanent AF, and their relationship with outcome are still poorly understood. Methods We examined AF patterns (paroxysmal, persistent and permanent), rate and predictors of AF progression, and outcomes in the PREFER (PREvention oF thromboembolic events-European Registry) in AF. The primary analysis was performed in the PREFER in AF prolongation dataset (n=3223 patients with AF with a complete 1-year follow-up, mean age 72±9 years, 40% women). Sensitivity analyses were performed using the PREFER in the AF study (n=6390 patients). Results AF progressed to more persistent types in 506 patients (17%). Permanent AF was associated with development of heart failure at 1 year (OR 1.80, 95% CI 1.06 to 3.07, p=0.03) compared with paroxysmal AF, which was confirmed in the entire cohort. In multivariable-adjusted models, sinus rhythm at baseline, AF duration, cardioversion, hyperthyroidism, valvular heart disease, diabetes mellitus and heart failure were predictors of AF progression (area under the receiver operating characteristic curve 0.60, 95% CI 0.57 to 0.63). Results were similar when we restricted analyses to patients with AF duration <1 year. AF progression showed an association with coronary events over 1 year (OR 2.27, 95% CI 1.22 to 4.19, p=0.0074). Conclusions Permanent AF at baseline was associated with incident heart failure. A substantial proportion of well-managed patients with AF showed AF progression over 1 year. AF progression itself was not strongly related to outcome and may indicate the need to refine the current classification of AF types to enhance clinical utility.