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DOI: 10.1055/s-0039-1683422
Non-Vitamin K Oral Anticoagulants in Comparison to Phenprocoumon in Geriatric and Non-Geriatric Patients with Non-Valvular Atrial Fibrillation
Publication History
25 September 2018
31 January 2019
Publication Date:
21 March 2019 (online)
Abstract
Geriatric characteristics such as high age, multi-morbidity, polypharmacy and frailty are common in patients with atrial fibrillation (AF). In a retrospective study using a German claims database, effectiveness (ischaemic stroke/systemic embolism) and safety (intracerebral, gastrointestinal and major extracranial bleeding) were compared in patients with non-valvular AF starting non-vitamin K oral antagonists (NOACs) (apixaban, dabigatran and rivaroxaban) and phenprocoumon. Cox proportional hazards models were used to calculate adjusted hazard ratios, and interaction terms of the treatment group and geriatric status (defined by age ≥75 years, frailty, ≥ 4 co-morbidities and polypharmacy) were entered into the model. A total of 42,562 and 27,939 patients initiated NOAC and phenprocoumon treatment (mean age 74 years ± 11, 51% male) with a follow-up time of 147,785 person-years. Note that 52.9% of patients were elderly, 50.8% were frail, 37.0% were co-morbid and 46.5% had polypharmacy. NOAC use was not associated with effectiveness and gastrointestinal bleeding, neither in geriatric nor in non-geriatric patients. The hazard of major extracranial and intracranial bleeding was significantly decreased for NOAC use, with similar risk reduction in geriatric and non-geriatric patients: major extracranial bleeding 0.70 (95% confidence interval [CI], 0.56–0.87) to 0.73 (95% CI, 0.60–0.89) for the geriatric groups and 0.71 (95% CI, 0.56–0.93) to 0.76 (0.59–0.98) for the non-geriatric groups (p-values for interaction > 0.6); and intracranial bleeding 0.52 (95% CI, 0.39–0.69) to 0.59 (95% CI, 0.47–0.73) for the geriatric groups and 0.54 (95% CI, 0.37–0.79) to 0.65 (95% CI, 0.49–0.86) for the non-geriatric groups (p-values for interaction > 0.2). Hence, NOACs showed similar effectiveness and superior safety in geriatric and non-geriatric patients.
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References
- 1 Krijthe BP, Kunst A, Benjamin EJ. , et al. Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur Heart J 2013; 34 (35) 2746-2751
- 2 Olesen JB, Lip GY, Hansen ML. , et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011; 342: d124
- 3 Connolly SJ, Ezekowitz MD, Yusuf S. , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
- 4 Patel MR, Mahaffey KW, Garg J. , et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
- 5 Granger CB, Alexander JH, McMurray JJ. , et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
- 6 Giugliano RP, Ruff CT, Braunwald E. , et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
- 7 Hugo GS, Figueiras-Graillet LM, Anguita M. , et al; FANTASIIA registry investigators (see Appendix). Oral anticoagulation in octogenarians with atrial fibrillation. Int J Cardiol 2016; 223: 87-90
- 8 Kirchhof P, Benussi S, Kotecha D. , et al; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37 (38) 2893-2962
- 9 Wilke T, Groth A, Mueller S. , et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Europace 2013; 15 (04) 486-493
- 10 Annoni G, Mazzola P. Real-world characteristics of hospitalized frail elderly patients with atrial fibrillation: can we improve the current prescription of anticoagulants?. J Geriatr Cardiol 2016; 13 (03) 226-232
- 11 Oqab Z, Pournazari P, Sheldon RS. What is the impact of frailty on prescription of anticoagulation in elderly patients with atrial fibrillation? A systematic review and meta-analysis. J Atr Fibrillation 2018; 10 (06) 1870
- 12 Broekhuizen K, Pothof A, de Craen AJ, Mooijaart SP. Characteristics of randomized controlled trials designed for elderly: a systematic review. PLoS One 2015; 10 (05) e0126709
- 13 Wehling M, Collins R, Gil VM. , et al. Appropriateness of oral anticoagulants for the long-term treatment of atrial fibrillation in older people: results of an evidence-based review and international consensus validation process (OAC-FORTA 2016). Drugs Aging 2017; 34 (07) 499-507
- 14 Stöllberger C, Finsterer J. Concerns about the use of new oral anticoagulants for stroke prevention in elderly patients with atrial fibrillation. Drugs Aging 2013; 30 (12) 949-958
- 15 Bahrmann P, Wehling M, Ropers D, Flohr J, Leischker A, Röther J. Optimal stroke prevention in the geriatric patient with atrial fibrillation: position paper of an interdisciplinary expert panel. Drug Res (Stuttg) 2015; 65 (10) 505-514
- 16 Sommerauer C, Schlender L, Krause M. , et al. Effectiveness and safety of vitamin K antagonists and new anticoagulants in the prevention of thromboembolism in atrial fibrillation in older adults - a systematic review of reviews and the development of recommendations to reduce inappropriate prescribing. BMC Geriatr 2017; 17 (Suppl. 01) 223
- 17 Perera V, Bajorek BV, Matthews S, Hilmer SN. The impact of frailty on the utilisation of antithrombotic therapy in older patients with atrial fibrillation. Age Ageing 2009; 38 (02) 156-162
- 18 Alnsasra H, Haim M, Senderey AB. , et al. Net clinical benefit of anticoagulant treatments in elderly patients with nonvalvular atrial fibrillation: experience from the real world. Heart Rhythm 2019; 16 (01) 31-37
- 19 Hohnloser SH, Basic E, Nabauer M. Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study. Clin Res Cardiol 2017; 106 (08) 618-628
- 20 Hohnloser SH, Basic E, Hohmann C, Nabauer M. Effectiveness and safety of non-vitamin K oral anticoagulants in comparison to phenprocoumon: data from 61,000 patients with atrial fibrillation. Thromb Haemost 2018; 118 (03) 526-538
- 21 Andersohn F, Walker J. Characteristics and external validity of the German Health Risk Institute (HRI) Database. Pharmacoepidemiol Drug Saf 2016; 25 (01) 106-109
- 22 Segal JB, Chang H-Y, Du Y, Walston JD, Carlson MC, Varadhan R. Development of a claims-based frailty indicator anchored to a well-established frailty phenotype. Med Care 2017; 55 (07) 716-722
- 23 Andreotti F, Rocca B, Husted S. , et al; ESC Thrombosis Working Group. Antithrombotic therapy in the elderly: expert position paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J 2015; 36 (46) 3238-3249
- 24 Halvorsen S, Atar D, Yang H. , et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J 2014; 35 (28) 1864-1872
- 25 Piccini JP, Hellkamp AS, Washam JB. , et al. Polypharmacy and the efficacy and safety of rivaroxaban versus warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation. Circulation 2016; 133 (04) 352-360
- 26 Steffel J, Giugliano RP, Braunwald E. , et al. Edoxaban versus warfarin in atrial fibrillation patients at risk of falling: ENGAGE AF-TIMI 48 analysis. J Am Coll Cardiol 2016; 68 (11) 1169-1178
- 27 Lee S, Monz BU, Clemens A, Brueckmann M, Lip GY. Representativeness of the dabigatran, apixaban and rivaroxaban clinical trial populations to real-world atrial fibrillation patients in the United Kingdom: a cross-sectional analysis using the General Practice Research Database. BMJ Open 2012; 2 (06) e001768
- 28 Metze C, Matzik AS, Scherner M. , et al. Impact of frailty on outcomes in patients undergoing percutaneous mitral valve repair. JACC Cardiovasc Interv 2017; 10 (19) 1920-1929
- 29 Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet 2013; 381 (9868): 752-762
- 30 Larsen TB, Skjøth F, Nielsen PB, Kjældgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ 2016; 353: i3189
- 31 Prochaska JH, Göbel S, Keller K. , et al. Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL. BMC Med 2015; 13: 14
- 32 Wallentin L, Lopes RD, Hanna M. , et al; Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Investigators. Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation 2013; 127 (22) 2166-2176