PREFER In Atrial Fibrillation Research Articles

Clinical Performance of Oral Anticoagulants in Elderly with Atrial Fibrillation and Low Body Weight: Insight into Italian Cohort of PREFER-AF and PREFER-AF Prolongation Registries.

Background: Elderly patients are at high risk of both ischaemic and bleeding events, and the low body weight is considered a risk factor for major bleeding in atrial fibrillation (AF) patients on anticoagulation therapy. The aim of our study was to compare the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus well-controlled vitamin-K antagonists (VKA) therapy among AF patients aged >75 years and with a body weight <60 kg in a prospective registry setting. Methods: Data for this study were sourced from the Italian cohorts of PREFER in AF and PREFER in AF PROLONGATION registries. The occurrence of a composite of stroke, transient ischemic attack and systemic embolism (thromboembolic events) was the primary effectiveness endpoint. The occurrence of major bleeding was the primary safety endpoint. All-cause hospitalizations and all-cause death were the secondary endpoints. The net clinical benefit (NCB) was calculated in order to obtain an integrated assessment of the anti-thromboembolic and pro-haemorrhagic effects of NOACs vs. VKA. Results: Overall, 522 patients were included; 225 were on treatment with NOACs and 317 patients with VKA. The NOAC group more frequently featured a higher BMI and a higher prevalence of history of stroke/TIA and insulin-requiring diabetes; conversely, heart failure and chronic liver disease were less frequent in the NAOC group. In the unmatched study population, 18 patients (3.6% in the NOAC vs. 3.2% in the VKA group, p = 0.79) experienced thromboembolic events; 19 patients (1.78% in the NOAC vs. 4.73% in the VKA group, p = 0.06) experienced major bleeding events; and 68 patients were hospitalized during the follow-up (9.3% vs. 14.8%, p = 0.06). After balancing for potential confounders by using the 1:1 propensity score matching technique, 426 patients (213 on NOAC and 213 on VKA) were selected. We found no significant differences in terms of thromboembolic events (3.76% vs. 4.69%, p = 0.63), major bleeding events (n: 1.88% vs. 4.22%, p = 0.15) and hospitalizations (9.9% vs. 16.9%, p = 0.06) between NOAC vs. VKA matched population. Based on these incidences, we found a positive net clinical benefit (+1.6) of NOACs vs. VKAs. Conclusions: These real-world data suggest the safety and effectiveness of using NOACs in elderly patients with low body weight.

Mortality Prediction of the CHA2DS2-VASc Score, the HAS-BLED Score, and Their Combination in Anticoagulated Patients with Atrial Fibrillation.

Background and Objectives: Atrial fibrillation (AF) is associated with increased mortality, predictors of which are poorly characterized. We investigated the predictive power of the commonly used CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65–75 years, sex category [female]), the HAS-BLED score (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [age ≥ 65 years], drugs/alcohol concomitantly), and their combination for mortality in AF patients. Methods: The PREvention oF thromboembolic events—European Registry in Atrial Fibrillation (PREFER in AF) was a prospective registry including AF patients across seven European countries. We used logistic regression to analyze the relationship between the CHA2DS2-VASc and HAS-BLED scores and outcomes, including mortality, at one year. We evaluated the performance of logistic regression models by discrimination measures (C-index and DeLong test) and calibration measures (Hosmer and Lemeshow goodness-of-fit and integrated discrimination improvement (IDI), with bootstrap techniques for internal validation. Results: In 5209 AF patients with complete information on both scores, average one-year mortality was 3.1%. We found strong gradients between stroke/systemic embolic events (SSE), major bleeding and—specifically—mortality for both CHA2DS2-VASc and HAS-BLED scores, with a similar C-statistic for event prediction. The predictive power of the models with both scores combined, removing overlapping components, was significantly enhanced (p < 0.01) compared to models including either CHA2DS2-VASc or HAS-BLED alone: for mortality, C-statistic: 0.740, compared to 0.707 for CHA2DS2-VASc or 0.646 for HAS-BLED alone. IDI analyses supported the significant improvement for the combined score model compared to separate score models for all outcomes. Conclusions: Both the CHA2DS2-VASc and the HAS-BLED scores predict mortality similarly in patients with AF, and a combination of their components increases prediction significantly. Such combination may be useful for investigational and—possibly—also clinical purposes.

Thromboembolic and bleeding risk in obese patients with atrial fibrillation according to different anticoagulation strategies

BackgroundData on the relationship between body mass index (BMI), thromboembolic events (TEE) and bleeding in patients with atrial fibrillation (AF) are controversial, and further evidence on the risk of such events in obese patients with AF receiving different anticoagulant therapies (OAC) is needed. Methods and resultsWe divided a total of 9330 participants from the prospective PREFER in AF and PREFER in AF PROLONGATION registries into BMI quartiles at baseline. Outcome measures were TEE and major bleeding complications at the 1-year follow-up. Without OAC, there was a ≥6-fold increase of TEE in the 4th vs other BMI quartiles (P = .019). OAC equalized the rates of TEE across different BMI strata. The occurrence of major bleeding was highest in patients with BMI in the 1st as well as in the 4th BMI quartile [OR 1.69, 95% CI 1.03–2.78, P = .039 and OR 1.86, 95% CI 1.13–3.04, P = .014 vs those in the 3rd quartile, respectively]. At propensity score-adjusted analysis, the incidence of TEE and major bleeding in obese patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K-antagonist anticoagulants (VKAs) was similar (P ≥ .34). ConclusionsOur real-world data suggest no obesity paradox for TEE in patients with AF. Obese patients are at higher risk of TEE, and here OAC dramatically reduces the risk of events. We here found a comparable clinical outcome with NOACs and VKAs in obese patients. Low body weight and obesity were also associated with bleeding, and therefore OAC with the best safety profile should be considered in this setting.

Risk factors for thromboembolic and bleeding events in anticoagulated patients with atrial fibrillation: the prospective, multicentre observational PREvention oF thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF)

ObjectivesWe identified factors associated with thromboembolic and bleeding events in two contemporary cohorts of anticoagulated patients with atrial fibrillation (AF), treated with either vitamin K antagonists (VKA) or non-VKA oral...

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

BackgroundEvidence 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. MethodsData 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. ResultsThe 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). ConclusionsAmong 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.

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

Background and objectivesTo assess thromboembolic and bleeding risks in patients with heart failure (HF) and atrial fibrillation (AF) according to HF type. MethodsWe 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. ResultsThe 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). ConclusionOur 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.

Oral anticoagulant use in octogenarian European patients with atrial fibrillation: A subanalysis of PREFER in AF

BackgroundFew studies describe oral anticoagulant (OAC) prescription practices in very elderly patients with atrial fibrillation (AF). MethodsIn this sub-analysis of the PREFER in AF study, performed in 2012, patients were stratified according to age (<80 [n=5565] and ≥80years [n=1660]) and OAC treatment. Factors associated with OAC prescription were analyzed in a multivariate logistic regression model with backward elimination of variables least associated with OAC use. ResultsPatients ≥80years presented with permanent AF more often (p<0.0001) and reported fatigue and dyspnea more frequently (p<0.0001) and palpitations less frequently (p<0.0001) than patients <80years. Hypertension, stroke, heart failure, coronary heart disease, peripheral arterial disease, cancer, chronic kidney disease, and prior major bleeding were significantly more frequent in ≥80years. Most patients were treated with OACs in both age groups. The overall use of vitamin K antagonists was similar in both groups (78.2% vs.78.2% p=0.98), while the use of non-vitamin K antagonist OACs was lower in the ≥80years old group than in the <80years group (4.5% vs. 6.6% p=0.001). Among patients ≥80years, prior stroke and heart failure were significantly associated with OAC use, whereas higher age, prior bleeding, paroxysmal AF, chronic hepatic disease, and difficulties with self-care were associated with no OAC use. ConclusionsThe current use of OAC in European AF patients was satisfactorily high in octogenarians, suggesting reasonable implementation of current guidelines. Interestingly, patients with poor quality of life were less often anticoagulated. This may warrant further studies.

Insulin-Requiring Versus Noninsulin-Requiring Diabetes and Thromboembolic Risk in Patients With Atrial Fibrillation: PREFER in AF

BackgroundDiabetes is a known risk predictor for thromboembolic events in patients with atrial fibrillation (AF), but no study has explored the prognostic weight of insulin in this setting. ObjectivesThis study evaluated the differential role of insulin versus no insulin therapy on thromboembolic risk in patients with diabetes and AF. MethodsWe accessed individual patient data from the prospective, real-world, multicenter, PREFER in AF (European Prevention of thromboembolic events-European Registry in Atrial Fibrillation). We compared the rates of stroke/systemic embolism at 1 year according to diabetes status (no diabetes, diabetes without insulin therapy, diabetes on insulin therapy). ResultsIn an overall population of 5,717 patients, 1,288 had diabetes, 22.4% of whom were on insulin. For patients with diabetes who were on insulin, there was a significantly increased risk of stroke/systemic embolism at 1 year versus either no diabetes (5.2% vs. 1.9%; hazard ratio: 2.89; 95% confidence interval: 1.67 to 5.02; p = 0.0002) or diabetes without insulin treatment (5.2% vs. 1.8%; hazard ratio: 2.96; 95% confidence interval: 1.49 to 5.87; p = 0.0019). Notably, rates of stroke/embolism were similar in patients with diabetes not receiving insulin versus patients without diabetes (hazard ratio: 0.97; 95% confidence interval: 0.58 to 1.61; p = 0.90). The selective predictive role of insulin-requiring diabetes was independent of potential confounders, including diabetes duration, and was maintained in various subpopulations, including the subgroup receiving anticoagulant therapy. ConclusionsIn this cohort of anticoagulated patients with AF, the sole presence of diabetes not requiring insulin did not imply an increased thromboembolic risk. Conversely, insulin-requiring diabetes contributed most, if not exclusively, to the overall increase of thromboembolic risk in AF.

Stroke in atrial fibrillation and improving the identification of ‘high‐risk’ patients: the crossroads of immunity and thrombosis

Stroke in atrial fibrillation and improving the identification of ‘high‐risk’ patients: the crossroads of immunity and thrombosis

Frequent and possibly inappropriate use of combination therapy with an oral anticoagulant and antiplatelet agents in patients with atrial fibrillation in Europe

PurposeCombined oral anticoagulant (OAC) and antiplatelet (AP) therapy is generally discouraged in atrial fibrillation (AF) outside of acute coronary syndromes or stenting because of increased bleeding. We evaluated its frequency...

Management of atrial fibrillation in seven European countries after the publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of the PREvention oF thromboemolic events—European Registry in Atrial Fibrillation (PREFER in AF)

AimsWe sought to describe the management of patients with atrial fibrillation (AF) in Europe after the release of the 2010 AF Guidelines of the European Society of Cardiology.Methods and resultsThe PREFER in AF registry enrolled consecutive patients with AF from January 2012 to January 2013 in 461 centres in seven European countries. Seven thousand two hundred and forty-three evaluable patients were enrolled, aged 71.5 ± 11 years, 60.1% male, CHA2DS2VASc score 3.4 ± 1.8 (mean ± standard deviation). Thirty per cent patients had paroxysmal, 24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent AF. Oral anticoagulation was used in the majority of patients: 4799 patients (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate 60–100 bpm). Half of the patients (50.7%) received rhythm control therapy by electrical cardioversion (18.1%), pharmacological cardioversion (19.5%), antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol 5.5%, dronedarone 4.0%), and catheter ablation (5.0%).ConclusionThe management of AF patients in 2012 has adapted to recent evidence and guideline recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given to over 80% of eligible patients, including those at risk for bleeding. Rate is often adequately controlled, and rhythm control therapy is widely used.

Patterns of anticoagulant underuse in European AF patients in 2012 - results from PREFER in AF registry

Background: The last focused update of the ESC guidelines for the management of atrial fibrillation (AF) recommended to use antithrombotic therapy for the prevention of thromboembolic events for all patients with AF except in those at low risk. Nevertheless, little is known about the impact of these recommendations in clinical practice of different European countries. Methods: The PREvention oF thromboembolic events – European Registry in Atrial Fibrillation (PREFER in AF) recruited unselected patients in Austria, France, Germany, Italy, Spain, Switzerland and the United Kingdom from Jan 2012 to Jan 2013. We report the data collected at enrolment into the study. Results: 7243 consecutive patients were enrolled. 5856 of them had a transthoracic echocardiography performed in the 12 months period prior to inclusion. While the overall prevalence of patients with CHA2DS2-VASc of 0 was very low, there were 1282 (17.7%) patients who did not receive antithrombotic therapy, including 808 patients (11.2%) who received antiplatelet (AP) therapy and 474 patients (6.5%) who had no preventive treatment at all. Patients who received AP or no preventive treatment had a lower prevalence of left atrial dilation than the overall population of the study (59.0% and 48.3% respectively vs. 70.1%, p<0.01) and were more frequently affected by paroxysmal AF (51.4% for AP group and 51.0% for no treatment vs. 30% overall, p<0.01). Those with no antithrombotic treatment tended to be younger than the average (67.4±14.3 years vs. 71.5±10.7 years, p<0.01), but no differences were seen for the AP group (70.9±11.8 years, p=0.11). Conclusions: There is still a significant proportion of patients with AF who, despite a raised risk of thromboembolism, do not receive appropriate treatment in Europe. Parameters associated with under-treatment suggest that this occurs more often in patients in initial stages of AF, despite the guideline recommendation of antithrombotic treatment only according to the risk profile.

The combined use of vitamin K antagonists and antiplatelet agents in atrial fibrillation - patterns of use in the European PREFER in AF registry

Purpose: The combined long-term use of vitamin K antagonists (VKA) and antiplatelet (AP) agents in patients with atrial fibrillation (AF) is generally discouraged because it entails increased risk of bleeding in the face of uncertain efficacy benefits. Therefore we evaluated the frequency of such prescription pattern and comorbidity associations. Methods: The PREvention oF thromboembolic events – European Registry in Atrial Fibrillation (PREFER in AF) prospectively enrolled patients with AF in France, Germany, Austria, Switzerland, Italy, Spain and the United Kingdom from Jan 2012 to Jan 2013. Here, we report the patterns of combined therapy with anticoagulants and (single or dual) AP therapy in this population. Results: In 7243 patients enrolled, 4799 (66.3%) were treated with a VKA (warfarin, phenprocoumon, acenocoumarol, fluindione), 808 (11.2%) with an AP alone, and 720 (9.9%) with a VKA + AP (88.8% with ASA, 21.0% with clopidogrel, 3.1% with another AP). Compared with patients only prescribed a VKA, patients on combination treatment had similar age and body mass index, but more often had paroxysmal (28.1 vs. 23.5%) or persistent (29.7 vs. 23.5%) AF (for both, p<0.01), a significantly higher prevalence of diabetes, obesity, dyslipidaemia and chronic renal insufficiency (for all, p<0.05), and significantly more frequent coexisting coronary heart disease (CHD) (58.9 vs. 19.0%; p<0.01) or peripheral arterial disease (PAD) (10.6 vs. 3.8%; p<0.01). Accordingly they had a higher mean CHA2DS2VASc score (3.8 vs. 3.5), and a higher mean HAS-BLED score (2.8 vs. 1.9) (for both, p<0.01). Most of the combination treatments were judged by all means inappropriate according to the 2010/2012 ESC guidelines, not being given because of recent stenting or an acute coronary syndrome. Detailed analyses on the appropriateness of combination therapy will be presented. Conclusions: The combined use of VKA and AP therapy is common in Europe, largely explained by the coexistence of AF with CHD or PAD, and not influenced by considerations on the risks of bleeding or thromboembolism. Such prescription patterns should be the target of appropriate guideline implementation programmes.