EJINME-02678; No of Pages 3 European Journal of Internal Medicine xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents Keywords: Atrial fibrillation Elderly Oral anticoagulant therapy Vitamin K antagonist Direct oral anticoagulants
Dear Editor,
Atrial fibrillation (AF) is a major risk factor for thromboembolism, particularly in patients over 75 years [1]. Despite multiples evidence of efficacy on thromboprophylaxis, oral anticoagulant therapy (OAT) with vitamin K antagonist (VKA) remains underused, especially in geriatric population [2]. In this setting, direct oral anticoagulant agents (DOACs) such as dabigatran etexilate and rivaroxaban appeared as a therapeutic alternative to VKA [3,4]. These drugs may have changed the trend in thromboprophylaxis in geriatric population. Therefore, we conducted a prospective descriptive study in the department of geriatric medicine of our university hospital on OAT in patients over 75 years admitted with AF at time of DOAC availability. Consecutive patients admitted in the department of geriatric medicine of our institution with the diagnosis of AF were prospectively included in the present study unless qualified for the exclusion criteria (valvular AF i.e. mitral stenosis or prosthetic heart valve, other indications for OAT and death before discharge). During the inclusion period, 708 patients were admitted in our department. Among these patients, 144 patients (20.3%), of whom 63 male (43.7%), presenting with AF were included in the present study. Clinical characteristics of patients included are shown in Table 1. Mean age was 85.4 ± 5.7 years (range 75 to 94 years). Sixty-five patients (45.1%) were aged ≥85 years. Hypertension was the most frequent associated condition found in 97 patients (67.4%). Previous stroke/transient ischemic attack (TIA)/systemic embolism was reported in 58 patients (40.3%). Mean CHA2DS2VASC score was 4.9 ± 1.4 (range 2 to 9). Among overall population, 84 patients (58.3%) were treated with OAT, either VKA in 64 patients (44.4%) or DOAC in 20 patients (13.9%). When comparing group of patients who were treated with OAT (either VKA or DOAC) with group of patients who were not treated with OAT, we found that the HASBLED risk score was lower in patient treated with OAT compared to patients not treated with OAT (2.5 ± 1.1 vs 3.0 ± 1.0 respectively, p = 0.01) and major hemorrhage was more frequent among patients who were not treated with OAT compared to those who were treated with OAT (36.4% vs 9.4%; p = 0.001). Otherwise, previous myocardial infarction, vascular diseases and coronary artery stenting were more frequent among patients without OAT compared to those with OAT (60.6% vs 24.1%;
p = 0.0002; 60.6% vs 34.9%; p = 0.01 and 48.5% vs 16.9%; p = 0.0005 respectively) and, anti-platelet agents used, either aspirin or clopidogrel, were more frequent among patients without OAT compared to those with OAT (45.4% vs 7.8%; p b 0.001 and 36.4% vs 9.4%; p = 0.001 respectively). When comparing patients treated with VKA with those treated with DOAC, we observed that patients in the VKA group were older than in the DOAC group (85.2 ± 4.9 vs 81.3 ± 5. years, p = 0.004). Otherwise, previous fall was found to be more frequent in patients treated with VKA compared to those treated with DOAC (40.6% vs 15.0%; p = 0.04). Finally, serum creatinine was higher in patients treated with VKA compared to those with DOAC (111 ± 46 μmol/l vs 86 ± 33 μmol/l; p = 0.03). Comparative tests between patients treated with OAT and patients not treated with OAT, and between patients treated with VKA and patients treated with DOAC are also represented in Table 1. We studied a population of geriatric AF-patients with both high thromboembolic risk (mean CHA2DS2-VASC score was 4.9 and 48% of patients presented with previous thromboembolic event) and high hemorrhagic risk (half of patients had a HASBLED score ≥3 and about 15% of patients had experienced major hemorrhage). Main findings are the following: Despite a high thromboembolic risk, only 58.3% of patients eligible for OAT were effectively treated. Otherwise, VKA remained the first intention treatment for thromboprophylaxis in population studied. Finally, clinical characteristics of patients treated with DOAC differ significantly from those treated with VKA. Indeed, patients with advanced age, previous fall and elevated serum creatinine level were more likely to be treated with VKA compared to DOAC. Taking account of advanced age and elevated hemorrhagic risk of patients included in our study, the rate of prescription of OAT was high in studied population. Indeed, in patients over 75 years, the rate of prescription was reported to be between 36.4% and 56% [5]. Partington et al. found that advanced age was the strongest predictor for warfarin non-use. [6] In the present study, we did not found age difference between patients with OAT and those without OAT. The high rate of previous TIA/stroke in patients included in our study (40.3%) might explain the relatively high rate of OAT use among them. On the other hand, we found that patients treated with VKA were more likely to be older than those treated with DOAC. Despite reassuring sub-group analysis in patients over 75 years, the lack of literature on “real-life” DOAC use for thromboprophylaxis in AFpatients over 75 years might explain this finding [7,8]. Risk of fall is the most often physician-cited reason for not prescribing OAT. However, the hemorrhagic risk related to fall is frequently overestimated as it has been demonstrated that patient with high thromboembolic risk related to AF would need to fall about 300 times a year for the risk of intracranial bleeding outweigh the benefit of warfarin in term of thromboprophylaxis [9]. Interestingly, in our study, patients treated with OAT and those without OAT reported falls in similar rates (40.6% vs 45.4% respectively). Nevertheless, we found
http://dx.doi.org/10.1016/j.ejim.2014.02.003 0953-6205/© 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Kayser M, et al, Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents, Eur J Intern Med (2014), http://dx.doi.org/10.1016/j.ejim.2014.02.003
e2
Number of patients Age (years) Male Hypertension Diabetes Congestive heart failure Previous stroke/TIA/systemic embolism Previous stroke Major hemorrhage CHA2DS2VASC score HASBLED score Type of AF Paroxysmal Persistent Permanent Previous fall Gastro intestinal bleeding Myocardial infarction Coronary artery angioplasty Antiplatelet therapy Aspirin Clopidogrel Serum creatinine (μmol/l)
All patients
OAT
No OAT
144 85.4 ± 5.6 43.7 (63) 67.4 (97) 40.3 (40) 25.0 (36) 40.3 (58) 29.9 (43) 14.6 (21) 4.9 ± 1.4 2.6 ± 1.1
84 84.3 ± 5.3 45.2 (38) 60.7 (51) 26.2 (22) 27.3 (23) 35.7 (30) 28.6 (24) 9.4 (8) 4.8 ± 1.5 2.5 ± 1.1
33 86.5 ± 6.1 45.4 (15) 72.7 (24) 33.3 (11) 24.2 (8) 33.3 (11) 33.3 (11) 36.4 (12) 5.1 ± 1.4 3.0 ± 1.0
47.2 (68) 6.9 (10) 45.8 (66) 37.5 (54) 12.5 (12) 30.5 (44) 21.5 (31)
36.9 (31) 10.7 (9) 52.4 (44) 34.9 (29) 11.9 (10) 23.8 (20) 16.7 (14)
60.6 (20) 3.0 (1) 36.4 (12) 45.4 (15) 21.2 (7) 60.6 (20) 48.5 (16)
18.7 (27) 22.9 (33) 104 ± 51
7.1 (6) 10.7 (9) 105 ± 44
45.4 (15) 36.4 (12) 118 ± 74
P value for OAT vs No OAT (khi2 or Wilcoxon)
VKA
DOAC
P value for VKA vs DOAC (khi2 or Wilcoxon)
64 85.2 ± 4.9 50.0 (32) 59.3 (38) 29.6 (16) 31.2 (20) 37.5 (24) 29.7 (19) 9.4 (6) 4.7 ± 1.6 2.5 ± 1.1
20 81.3 ± 5.5 30 (6) 65 (13) 40 (8) 15 (3) 30 (6) 25 (5) 10 (2) 4.9 ± 1.3 2.5 ± 1.2
0.004⁎ 0.16 0.47 0.24 0.19 0.64 0.77 0.88 0.47 0.89
0.29 0.20 0.0002⁎ 0.0005⁎
37.5 (24) 6.3 (4) 56.2 (36) 40.6 (26) 10.9 (7) 23.4 (15) 14.1 (9)
35 (7) 20 (4) 40 (8) 15 (3) 15 (3) 25 (5) 25 (5)
0.046⁎ 0.57 0.79 0.21
b0.0001⁎ 0.001⁎ 0.95
7.8 (5) 9.4 (6) 110 ± 46
5 (1) 5 (1) 86.5 ± 33
0.71 0.43 0.03⁎
0.13 0.97 0.25 0.46 0.70 0.77 0.64 0.0006⁎ 0.29 0.01⁎ 0.06
Values are % (n); continuous data are given as mean ± standard deviation. Statistical comparison were performed with either khi2 (continuous values) or Wilcoxon (categorical values) tests. AF, atrial fibrillation; OAT, oral anticoagulant therapy; DOAC, direct oral anticoagulant agent; VKA, vitamin K antagonist; TIA, transient ischemic attack. ⁎ P values b0.05.
0.14
Letter to the Editor
Please cite this article as: Kayser M, et al, Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents, Eur J Intern Med (2014), http://dx.doi.org/10.1016/j.ejim.2014.02.003
Table 1 Univariate analysis comparing clinical characteristics of patients treated with OAT and patients not treated with OAT and of patients treated with VKA and patients treated with DOAC.
Letter to the Editor
that the rate of falls was significantly higher in patients treated with VKA compared to those with DOAC. This fact might be explained by the current absence of specific antidote against DOAC quickly reversing anticoagulation in case of severe bleeding. Development of specific DOAC antidote is currently ongoing and might change reservations of use of this therapeutic class among patients who are thought to be at elevated hemorrhagic risk and/or prone to fall. Finally, similar to geriatric patients, patients with AF and mild to moderate renal insufficiency are thought to represent a sub-group of patients with both increased thomboembolic and hemorrhagic risks [10]. Dabigatran etexilate and rivaroxaban are respectively cleared for 80% and 35% by the kidney. In our study, we found that serum creatinine level was significantly lower in patients treated with DOAC which are renal cleared compared to patients treated with VKA. Mainly two reasons might explain this finding. First, due to loss of muscular mass in geriatric patients, the accuracy of creatinine clearance estimation is low. Otherwise, geriatric patients are exposed to functional changes during acute illness and drug interaction potentially leading to acute renal impairment and thus DOAC overdose if prescribed. The fear of this increased hemorrhagic risk during acute renal failure might have involved the prescription of VKA treatment instead of DOAC in patients of our study with chronic mildly to moderately elevated serum creatinine. In conclusion, learning points of the present study are the following: - Despite the recent availability of DOAC for thromboprophylaxis in non-valvular AF patients, the rate of OAT use remained low (58%) in geriatric patients, - Patients with elevated HASBLED score, previous major hemorrhage, previous myocardial infarction, coronary artery stenting and vascular diseases or undergoing anti platelet therapy were more likely to not receive OAT. - Vitamin K antagonist therapy remained the main antithrombotic therapy decided in geriatric patients with non-valvular AF, compared to DOAC, especially in patients with advanced age, elevated serum creatinine and history of previous fall. Conflict of interests The authors state that they have no conflicts of interest.
e3
[2] Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493–503. [3] Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–51. [4] Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91. [5] Hylek EM, D'Antonio J, Evans-Molina C, Shea C, Henault LE, Regan S. Translating the results of randomized trials into clinical practice: the challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation. Stroke 2006;37:1075–80. [6] Partington SL, Abid S, Teo K, Oczkowski W, O'Donnell MJ. Pre-admission warfarin use in patients with acute ischemic stroke and atrial fibrillation: the appropriate use and barriers to oral anticoagulant therapy. Thromb Res 2007;120:663–9. [7] Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of longterm anticoagulant therapy (RE-LY) trial. Circulation 2011;123:2363–72. [8] Halperin JL, Wojdyla D, Piccini JP, Lokhnygina Y, Patel MR, Breithardt G, et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the ROCKET-AF trial. Stroke 2012;43:A148. [9] Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999;159:677–85. [10] Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go AS, et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors in Atrial fibrillation) study cohorts. Circulation 2013;127:224–32.
Marjorie Kayser Yves Frances Department of Geriatric Medecine, Centre Hospitalier Universitaire Nord, Marseille, France Laurent Bonello Franck Paganelli Michael Peyrol Department of Cardiology, Centre Hospitalier Universitaire Nord, Marseille, France Corresponding author at: Division of Cardiology, Centre Hospitalier Universitaire Nord, Chemin des Bourrely, 13915 Marseille, Cedex 20, France. Tel.: +33 4 91 96 86 83; fax: +33 4 91 96 89 79. E-mail address: [email protected]
References [1] Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983–8.
2 February 2014 Available online xxxx
Please cite this article as: Kayser M, et al, Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents, Eur J Intern Med (2014), http://dx.doi.org/10.1016/j.ejim.2014.02.003
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents Keywords: Atrial fibrillation Elderly Oral anticoagulant therapy Vitamin K antagonist Direct oral anticoagulants
Dear Editor,
Atrial fibrillation (AF) is a major risk factor for thromboembolism, particularly in patients over 75 years [1]. Despite multiples evidence of efficacy on thromboprophylaxis, oral anticoagulant therapy (OAT) with vitamin K antagonist (VKA) remains underused, especially in geriatric population [2]. In this setting, direct oral anticoagulant agents (DOACs) such as dabigatran etexilate and rivaroxaban appeared as a therapeutic alternative to VKA [3,4]. These drugs may have changed the trend in thromboprophylaxis in geriatric population. Therefore, we conducted a prospective descriptive study in the department of geriatric medicine of our university hospital on OAT in patients over 75 years admitted with AF at time of DOAC availability. Consecutive patients admitted in the department of geriatric medicine of our institution with the diagnosis of AF were prospectively included in the present study unless qualified for the exclusion criteria (valvular AF i.e. mitral stenosis or prosthetic heart valve, other indications for OAT and death before discharge). During the inclusion period, 708 patients were admitted in our department. Among these patients, 144 patients (20.3%), of whom 63 male (43.7%), presenting with AF were included in the present study. Clinical characteristics of patients included are shown in Table 1. Mean age was 85.4 ± 5.7 years (range 75 to 94 years). Sixty-five patients (45.1%) were aged ≥85 years. Hypertension was the most frequent associated condition found in 97 patients (67.4%). Previous stroke/transient ischemic attack (TIA)/systemic embolism was reported in 58 patients (40.3%). Mean CHA2DS2VASC score was 4.9 ± 1.4 (range 2 to 9). Among overall population, 84 patients (58.3%) were treated with OAT, either VKA in 64 patients (44.4%) or DOAC in 20 patients (13.9%). When comparing group of patients who were treated with OAT (either VKA or DOAC) with group of patients who were not treated with OAT, we found that the HASBLED risk score was lower in patient treated with OAT compared to patients not treated with OAT (2.5 ± 1.1 vs 3.0 ± 1.0 respectively, p = 0.01) and major hemorrhage was more frequent among patients who were not treated with OAT compared to those who were treated with OAT (36.4% vs 9.4%; p = 0.001). Otherwise, previous myocardial infarction, vascular diseases and coronary artery stenting were more frequent among patients without OAT compared to those with OAT (60.6% vs 24.1%;
p = 0.0002; 60.6% vs 34.9%; p = 0.01 and 48.5% vs 16.9%; p = 0.0005 respectively) and, anti-platelet agents used, either aspirin or clopidogrel, were more frequent among patients without OAT compared to those with OAT (45.4% vs 7.8%; p b 0.001 and 36.4% vs 9.4%; p = 0.001 respectively). When comparing patients treated with VKA with those treated with DOAC, we observed that patients in the VKA group were older than in the DOAC group (85.2 ± 4.9 vs 81.3 ± 5. years, p = 0.004). Otherwise, previous fall was found to be more frequent in patients treated with VKA compared to those treated with DOAC (40.6% vs 15.0%; p = 0.04). Finally, serum creatinine was higher in patients treated with VKA compared to those with DOAC (111 ± 46 μmol/l vs 86 ± 33 μmol/l; p = 0.03). Comparative tests between patients treated with OAT and patients not treated with OAT, and between patients treated with VKA and patients treated with DOAC are also represented in Table 1. We studied a population of geriatric AF-patients with both high thromboembolic risk (mean CHA2DS2-VASC score was 4.9 and 48% of patients presented with previous thromboembolic event) and high hemorrhagic risk (half of patients had a HASBLED score ≥3 and about 15% of patients had experienced major hemorrhage). Main findings are the following: Despite a high thromboembolic risk, only 58.3% of patients eligible for OAT were effectively treated. Otherwise, VKA remained the first intention treatment for thromboprophylaxis in population studied. Finally, clinical characteristics of patients treated with DOAC differ significantly from those treated with VKA. Indeed, patients with advanced age, previous fall and elevated serum creatinine level were more likely to be treated with VKA compared to DOAC. Taking account of advanced age and elevated hemorrhagic risk of patients included in our study, the rate of prescription of OAT was high in studied population. Indeed, in patients over 75 years, the rate of prescription was reported to be between 36.4% and 56% [5]. Partington et al. found that advanced age was the strongest predictor for warfarin non-use. [6] In the present study, we did not found age difference between patients with OAT and those without OAT. The high rate of previous TIA/stroke in patients included in our study (40.3%) might explain the relatively high rate of OAT use among them. On the other hand, we found that patients treated with VKA were more likely to be older than those treated with DOAC. Despite reassuring sub-group analysis in patients over 75 years, the lack of literature on “real-life” DOAC use for thromboprophylaxis in AFpatients over 75 years might explain this finding [7,8]. Risk of fall is the most often physician-cited reason for not prescribing OAT. However, the hemorrhagic risk related to fall is frequently overestimated as it has been demonstrated that patient with high thromboembolic risk related to AF would need to fall about 300 times a year for the risk of intracranial bleeding outweigh the benefit of warfarin in term of thromboprophylaxis [9]. Interestingly, in our study, patients treated with OAT and those without OAT reported falls in similar rates (40.6% vs 45.4% respectively). Nevertheless, we found
http://dx.doi.org/10.1016/j.ejim.2014.02.003 0953-6205/© 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Kayser M, et al, Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents, Eur J Intern Med (2014), http://dx.doi.org/10.1016/j.ejim.2014.02.003
e2
Number of patients Age (years) Male Hypertension Diabetes Congestive heart failure Previous stroke/TIA/systemic embolism Previous stroke Major hemorrhage CHA2DS2VASC score HASBLED score Type of AF Paroxysmal Persistent Permanent Previous fall Gastro intestinal bleeding Myocardial infarction Coronary artery angioplasty Antiplatelet therapy Aspirin Clopidogrel Serum creatinine (μmol/l)
All patients
OAT
No OAT
144 85.4 ± 5.6 43.7 (63) 67.4 (97) 40.3 (40) 25.0 (36) 40.3 (58) 29.9 (43) 14.6 (21) 4.9 ± 1.4 2.6 ± 1.1
84 84.3 ± 5.3 45.2 (38) 60.7 (51) 26.2 (22) 27.3 (23) 35.7 (30) 28.6 (24) 9.4 (8) 4.8 ± 1.5 2.5 ± 1.1
33 86.5 ± 6.1 45.4 (15) 72.7 (24) 33.3 (11) 24.2 (8) 33.3 (11) 33.3 (11) 36.4 (12) 5.1 ± 1.4 3.0 ± 1.0
47.2 (68) 6.9 (10) 45.8 (66) 37.5 (54) 12.5 (12) 30.5 (44) 21.5 (31)
36.9 (31) 10.7 (9) 52.4 (44) 34.9 (29) 11.9 (10) 23.8 (20) 16.7 (14)
60.6 (20) 3.0 (1) 36.4 (12) 45.4 (15) 21.2 (7) 60.6 (20) 48.5 (16)
18.7 (27) 22.9 (33) 104 ± 51
7.1 (6) 10.7 (9) 105 ± 44
45.4 (15) 36.4 (12) 118 ± 74
P value for OAT vs No OAT (khi2 or Wilcoxon)
VKA
DOAC
P value for VKA vs DOAC (khi2 or Wilcoxon)
64 85.2 ± 4.9 50.0 (32) 59.3 (38) 29.6 (16) 31.2 (20) 37.5 (24) 29.7 (19) 9.4 (6) 4.7 ± 1.6 2.5 ± 1.1
20 81.3 ± 5.5 30 (6) 65 (13) 40 (8) 15 (3) 30 (6) 25 (5) 10 (2) 4.9 ± 1.3 2.5 ± 1.2
0.004⁎ 0.16 0.47 0.24 0.19 0.64 0.77 0.88 0.47 0.89
0.29 0.20 0.0002⁎ 0.0005⁎
37.5 (24) 6.3 (4) 56.2 (36) 40.6 (26) 10.9 (7) 23.4 (15) 14.1 (9)
35 (7) 20 (4) 40 (8) 15 (3) 15 (3) 25 (5) 25 (5)
0.046⁎ 0.57 0.79 0.21
b0.0001⁎ 0.001⁎ 0.95
7.8 (5) 9.4 (6) 110 ± 46
5 (1) 5 (1) 86.5 ± 33
0.71 0.43 0.03⁎
0.13 0.97 0.25 0.46 0.70 0.77 0.64 0.0006⁎ 0.29 0.01⁎ 0.06
Values are % (n); continuous data are given as mean ± standard deviation. Statistical comparison were performed with either khi2 (continuous values) or Wilcoxon (categorical values) tests. AF, atrial fibrillation; OAT, oral anticoagulant therapy; DOAC, direct oral anticoagulant agent; VKA, vitamin K antagonist; TIA, transient ischemic attack. ⁎ P values b0.05.
0.14
Letter to the Editor
Please cite this article as: Kayser M, et al, Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents, Eur J Intern Med (2014), http://dx.doi.org/10.1016/j.ejim.2014.02.003
Table 1 Univariate analysis comparing clinical characteristics of patients treated with OAT and patients not treated with OAT and of patients treated with VKA and patients treated with DOAC.
Letter to the Editor
that the rate of falls was significantly higher in patients treated with VKA compared to those with DOAC. This fact might be explained by the current absence of specific antidote against DOAC quickly reversing anticoagulation in case of severe bleeding. Development of specific DOAC antidote is currently ongoing and might change reservations of use of this therapeutic class among patients who are thought to be at elevated hemorrhagic risk and/or prone to fall. Finally, similar to geriatric patients, patients with AF and mild to moderate renal insufficiency are thought to represent a sub-group of patients with both increased thomboembolic and hemorrhagic risks [10]. Dabigatran etexilate and rivaroxaban are respectively cleared for 80% and 35% by the kidney. In our study, we found that serum creatinine level was significantly lower in patients treated with DOAC which are renal cleared compared to patients treated with VKA. Mainly two reasons might explain this finding. First, due to loss of muscular mass in geriatric patients, the accuracy of creatinine clearance estimation is low. Otherwise, geriatric patients are exposed to functional changes during acute illness and drug interaction potentially leading to acute renal impairment and thus DOAC overdose if prescribed. The fear of this increased hemorrhagic risk during acute renal failure might have involved the prescription of VKA treatment instead of DOAC in patients of our study with chronic mildly to moderately elevated serum creatinine. In conclusion, learning points of the present study are the following: - Despite the recent availability of DOAC for thromboprophylaxis in non-valvular AF patients, the rate of OAT use remained low (58%) in geriatric patients, - Patients with elevated HASBLED score, previous major hemorrhage, previous myocardial infarction, coronary artery stenting and vascular diseases or undergoing anti platelet therapy were more likely to not receive OAT. - Vitamin K antagonist therapy remained the main antithrombotic therapy decided in geriatric patients with non-valvular AF, compared to DOAC, especially in patients with advanced age, elevated serum creatinine and history of previous fall. Conflict of interests The authors state that they have no conflicts of interest.
e3
[2] Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493–503. [3] Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–51. [4] Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91. [5] Hylek EM, D'Antonio J, Evans-Molina C, Shea C, Henault LE, Regan S. Translating the results of randomized trials into clinical practice: the challenge of warfarin candidacy among hospitalized elderly patients with atrial fibrillation. Stroke 2006;37:1075–80. [6] Partington SL, Abid S, Teo K, Oczkowski W, O'Donnell MJ. Pre-admission warfarin use in patients with acute ischemic stroke and atrial fibrillation: the appropriate use and barriers to oral anticoagulant therapy. Thromb Res 2007;120:663–9. [7] Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of longterm anticoagulant therapy (RE-LY) trial. Circulation 2011;123:2363–72. [8] Halperin JL, Wojdyla D, Piccini JP, Lokhnygina Y, Patel MR, Breithardt G, et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the ROCKET-AF trial. Stroke 2012;43:A148. [9] Man-Son-Hing M, Nichol G, Lau A, Laupacis A. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med 1999;159:677–85. [10] Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go AS, et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors in Atrial fibrillation) study cohorts. Circulation 2013;127:224–32.
Marjorie Kayser Yves Frances Department of Geriatric Medecine, Centre Hospitalier Universitaire Nord, Marseille, France Laurent Bonello Franck Paganelli Michael Peyrol Department of Cardiology, Centre Hospitalier Universitaire Nord, Marseille, France Corresponding author at: Division of Cardiology, Centre Hospitalier Universitaire Nord, Chemin des Bourrely, 13915 Marseille, Cedex 20, France. Tel.: +33 4 91 96 86 83; fax: +33 4 91 96 89 79. E-mail address: [email protected]
References [1] Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983–8.
2 February 2014 Available online xxxx
Please cite this article as: Kayser M, et al, Oral anticoagulant treatment in geriatric patients with nonvalvular atrial fibrillation in the era of direct oral anticoagulant agents, Eur J Intern Med (2014), http://dx.doi.org/10.1016/j.ejim.2014.02.003
