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)
Language English Country England, Great Britain Media electronic
Document type Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't
Grant support
CDF-2015-08-074
Department of Health - United Kingdom
PubMed
30928922
PubMed Central
PMC6475354
DOI
10.1136/bmjopen-2018-022478
PII: bmjopen-2018-022478
Knihovny.cz E-resources
- Keywords
- anticoagulation, atrial fibrillation, major bleeding, risk stratification, thromboembolism,
- MeSH
- Anticoagulants adverse effects therapeutic use MeSH
- Administration, Oral MeSH
- Stroke etiology prevention & control MeSH
- Atrial Fibrillation complications drug therapy MeSH
- Risk Assessment MeSH
- International Normalized Ratio MeSH
- Hemorrhage chemically induced epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Multivariate Analysis MeSH
- Follow-Up Studies MeSH
- Prospective Studies MeSH
- Registries MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Failure epidemiology etiology MeSH
- Ischemic Attack, Transient epidemiology etiology MeSH
- Thromboembolism etiology prevention & control MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe epidemiology MeSH
- Names of Substances
- Anticoagulants MeSH
OBJECTIVES: We 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 anticoagulants (NOACs). DESIGN: Prospective, multicentre observational study. SETTING: 461 centres in seven European countries. PARTICIPANTS: 5310 patients receiving a VKA (PREvention oF thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF), derivation cohort) and 3156 patients receiving a NOAC (PREFER in AF Prolongation, validation cohort) for stroke prevention in AF. OUTCOME MEASURES: Risk factors for thromboembolic events (ischaemic stroke, systemic embolism) and major bleeding (gastrointestinal bleeding, intracerebral haemorrhage and other life-threatening bleeding). RESULTS: The mean age of patients enrolled in the PREFER in AF registry was 72±10 years, 40% were female and the mean CHA2DS2-VASc Score was 3.5±1.7. The incidence of thromboembolic and major bleeding events was 2.34% (95% CI 1.93% to 2.74%) and 2.84% (95% CI 2.41% to 3.33%) after 1-year of follow-up, respectively.Abnormal liver function, prior stroke or transient ischaemic attack, labile international normalised ratio (INR), concomitant therapy with antiplatelet or non-steroidal anti-inflammatory drugs, heart failure and older age (≥75 years) were independently associated with both thromboembolic and major bleeding events.With the exception of unstable INR values, these risk factors were validated in patients treated with NOACs (PREFER in AF Prolongation Study, 72±9 years, 40% female, CHA2DS2-VASc 3.3±1.6). For each single point decrease on a modifiable bleeding risk scale we observed a 30% lower risk for major bleeding events (OR 0.70, 95% CI 0.64 to 0.76, p<0.01) and a 28% lower rate of thromboembolic events (OR 0.72, 95% CI 0.66 to 0.82, p<0.01). CONCLUSION: Attending to modifiable risk factors is an important treatment target in anticoagulated AF patients to reduce thromboembolic and bleeding events. Initiation of anticoagulation in those at risk of stroke should not be prevented by elevated bleeding risk scores.
3rd Medical Department Cardiology and Intensive Care Medicine Wilhelminen Hospital Vienna Austria
Cardiology Medical Faculty Pilsen Charles University Pilsen Czech Republic
Cardiology Sigmund Freud University Medical School Vienna Austria
Daiichi Sankyo Europe Munich Germany
Department of Cardiology Medical University of Vienna Vienna Austria
Department of Cardiology St Bartholomew's Hospital London UK
Department of Cardiovascular Sciences Campus Bio Medico University of Rome Rome Italy
Institute for Cardiometabolic Diseases Karl Landsteiner Society St Pölten Austria
University of Pisa and Division of Cardiology Pisa University Hospital Pisa Italy
See more in PubMed
Kirchhof P, Benussi S, Kotecha D, et al. . 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–962. 10.1093/eurheartj/ehw210 PubMed DOI
Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857–67. 10.7326/0003-4819-146-12-200706190-00007 PubMed DOI
Freedman B, Martinez C, Katholing A, et al. . Residual risk of stroke and death in anticoagulant-treated patients with atrial fibrillation. JAMA Cardiol 2016;1:366–8. 10.1001/jamacardio.2016.0393 PubMed DOI
Olesen JB, Lip GY, Lindhardsen J, et al. . Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study. Thromb Haemost 2011;106:739–49. 10.1160/TH11-05-0364 PubMed DOI
Pancholy SB, Sharma PS, Pancholy DS, et al. . Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants. Am J Cardiol 2014;113:485–90. 10.1016/j.amjcard.2013.10.035 PubMed DOI
Ruff CT, Giugliano RP, Braunwald E, et al. . Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955–62. 10.1016/S0140-6736(13)62343-0 PubMed DOI
Senoo K, Lip GY, Lane DA, et al. . Residual risk of stroke and death in anticoagulated patients according to the type of atrial fibrillation: AMADEUS trial. Stroke 2015;46:2523–8. 10.1161/STROKEAHA.115.009487 PubMed DOI
Camm AJ, Amarenco P, Haas S, et al. . XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016;37:1145–53. 10.1093/eurheartj/ehv466 PubMed DOI PMC
Li C, Engström G, Hedblad B, et al. . Blood pressure control and risk of stroke: a population-based prospective cohort study. Stroke 2005;36:725–30. 10.1161/01.STR.0000158925.12740.87 PubMed DOI
Connolly SJ, Pogue J, Eikelboom J, et al. . Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 2008;118:2029–37. 10.1161/CIRCULATIONAHA.107.750000 PubMed DOI
Trelle S, Reichenbach S, Wandel S, et al. . Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 2011;342:c7086 10.1136/bmj.c7086 PubMed DOI PMC
Hansen ML, Sørensen R, Clausen MT, et al. . Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010;170:1433–41. 10.1001/archinternmed.2010.271 PubMed DOI
Emberson JR, Shaper AG, Wannamethee SG, et al. . Alcohol intake in middle age and risk of cardiovascular disease and mortality: accounting for intake variation over time. Am J Epidemiol 2005;161:856–63. 10.1093/aje/kwi111 PubMed DOI
Go AS, Chertow GM, Fan D, et al. . Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296–305. 10.1056/NEJMoa041031 PubMed DOI
Targher G, Arcaro G. Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 2007;191:235–40. 10.1016/j.atherosclerosis.2006.08.021 PubMed DOI
Burn J, Dennis M, Bamford J, et al. . Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke 1994;25:333–7. 10.1161/01.STR.25.2.333 PubMed DOI
Wolf PA, D’Agostino RB, Belanger AJ, et al. . Probability of stroke: a risk profile from the Framingham Study. Stroke 1991;22:312–8. 10.1161/01.STR.22.3.312 PubMed DOI
Lip GY, Frison L, Halperin JL, et al. . Identifying patients at high risk for stroke despite anticoagulation: a comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort. Stroke 2010;41:2731–8. 10.1161/STROKEAHA.110.590257 PubMed DOI
Barnes GD, Gu X, Haymart B, et al. . The predictive ability of the CHADS2 and CHA2DS2-VASc scores for bleeding risk in atrial fibrillation: the MAQI(2) experience. Thromb Res 2014;134:294–9. 10.1016/j.thromres.2014.05.034 PubMed DOI
Roldán V, Marín F, Manzano-Fernández S, et al. . The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 2013;62:2199–204. 10.1016/j.jacc.2013.08.1623 PubMed DOI
Kirchhof P, Ammentorp B, Darius H, et al. . 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). Europace 2014;16:6–14. 10.1093/europace/eut263 PubMed DOI PMC
Marcucci M, Lip GY, Nieuwlaat R, et al. . Stroke and bleeding risk co-distribution in real-world patients with atrial fibrillation: the Euro Heart Survey. Am J Med 2014;127:979–86. 10.1016/j.amjmed.2014.05.003 PubMed DOI
Apostolakis S, Lane DA, Guo Y, et al. . Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study. J Am Coll Cardiol 2012;60:861–7. 10.1016/j.jacc.2012.06.019 PubMed DOI
Lip GY, Frison L, Halperin JL, et al. . Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol 2011;57:173–80. 10.1016/j.jacc.2010.09.024 PubMed DOI
DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45. 10.2307/2531595 PubMed DOI
Pisters R, Lane DA, Nieuwlaat R, et al. . A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010;138:1093–100. 10.1378/chest.10-0134 PubMed DOI
Dzeshka MS, Lip GY. Specific risk scores for specific purposes: use CHA2DS2-VASc for assessing stroke risk, and use HAS-BLED for assessing bleeding risk in atrial fibrillation. Thromb Res 2014;134:217–8. 10.1016/j.thromres.2014.06.003 PubMed DOI
Senoo K, Proietti M, Lane DA, et al. . Evaluation of the HAS-BLED, ATRIA, and ORBIt bleeding risk scores in patients with atrial fibrillation taking warfarin. Am J Med 2016;129:600–7. 10.1016/j.amjmed.2015.10.001 PubMed DOI
Proietti M, Senoo K, Lane DA, et al. . Major bleeding in patients with non-valvular atrial fibrillation: impact of time in therapeutic range on contemporary bleeding risk scores. Sci Rep 2016;6:24376 10.1038/srep24376 PubMed DOI PMC
Szummer K, Gasparini A, Eliasson S, et al. . Time in therapeutic range and outcomes after warfarin initiation in newly diagnosed atrial fibrillation patients with renal dysfunction. J Am Heart Assoc 2017;6 10.1161/JAHA.116.004925 PubMed DOI PMC
Mueller S, Meinecke A-K, Buchwald S, et al. . Real-world adherence to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: results of an international survey. Blood 2017;130(Suppl 1):4726–26.
Flaker GC, Gruber M, Connolly SJ, et al. . Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials. Am Heart J 2006;152:967–73. 10.1016/j.ahj.2006.06.024 PubMed DOI
Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med 1994;331:1675–9. 10.1056/NEJM199412223312502 PubMed DOI
Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011;365:147–56. 10.1056/NEJMra1011170 PubMed DOI
Banerjee A, Lane DA, Torp-Pedersen C, et al. . Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012;107:584–9. 10.1160/TH11-11-0784 PubMed DOI
Friberg L, Rosenqvist M, Lip GY. Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012;125:2298–307. 10.1161/CIRCULATIONAHA.111.055079 PubMed DOI
