- Email: [email protected]
Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately controlled
EJINME-03118; No of Pages 2 European Journal of Internal Medicine xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letters to the Editor Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately controlled Keywords: Atrial fibrillation Vitamin K antagonist Therapeutic behavior Inertia
In the majority of patients with atrial fibrillation (AF), long-term oral anticoagulation is necessary to reduce the risk of stroke. Although effective, vitamin K antagonists (VKAs) exhibit many limitations [1,2]. Despite that, they are still widely used in clinical practice [3]. Maintaining the international normalized ratio (INR) of patients within the therapeutic range is crucial to reduce the risk of thromboembolic events with no marked increase on hemorrhagic complications [2]. Overall, it has been reported that around 35–50% of patients treated with VKAs have an inadequate INR control [4,5]. Different factors (i.e. polymedication, comorbidities, etc.) have been associated with this poor INR control [4,5]. However, little is known about the attitude of physicians when time in therapeutic range (TTR) is out of range. The aim of this study was to examine the therapeutic behavior of primary care physicians in patients taking VKAs not adequately controlled. PAULA was a cross-sectional/retrospective study, involving patients with nonvalvular AF attended in primary care setting in Spain, who had received treatment with VKAs for at least the last year [5]. The study was approved by the Clinical Research Ethics Committee of the University Hospital La Paz of Madrid. All patients signed the written informed consent before inclusion. The study involved a single visit that coincided with one of the patient's regular follow-up visits. Data were collected from the medical history and physician interview. To assess patients' INR control, the TTR in the past 12 months was calculated at a core lab by both the direct method (proportion of INR values within therapeutic range) and the Rosendaal method. Labile INR was considered when TTR b 60% [5]. A total of 1524 patients (mean age 77.4 ± 8.7 years; 48.6% women; 64.2% with permanent AF) were analyzed. The mean time from AF diagnosis to the study date was 6.0 ± 4.2 years and 12.3% of patients had a history of labile INR. Mean CHADS2 was 2.3 ± 1.2, CHA2DS2-VASc 3.9 ± 1.5 and HAS-BLED 1.6 ± 0.9. The percent TTR was 63.2 ± 17.9% and 69.0 ± 17.7% according to the direct and Rosendaal methods, respectively and a 56.9% and 60.6% of patients achieved an adequate INR control, respectively. In the last 6 months, the mean number of anticoagulation controlrelated visits to the primary care physician was 6.8 ± 5.5, to the primary care nurse 9.7 ± 5.2, to the specialist 1.1 ± 2.2 and to the emergency department 0.3 ± 0.9 (Table 1). The total number of INR readings recorded in the previous 12 months was 21,982 (15.9 ± 4.2 in those individuals with poor INR control vs 13.3 ± 3.1 in those with good INR control
[direct method]; p b 0.001; and 15.9 ± 4.3 vs 13.3 ± 3.1, respectively; p b 0.001 [Rosendaal method]). In 30.5% of the INR readings, the anticoagulant dose was modified (72.1% in case of INR out of range vs 3.7% in those patients with INR within range interval; p b 0.0001). Anticoagulant therapy was modified by 25.4% of physicians (59.9% modified the dosage of AVK; 37.0% switched to another oral anticoagulant; 11.4% referred to another specialist; and 3.1% performed other action (Table 1). In 65.0% of patients, the physician considered that the patient had a good INR control. The PAULA study included a broad sample of patients representative of the whole Spanish population with nonvalvular AF attended in primary care, with a high number of INR controls and a long follow-up period. In line with other studies, our data showed that in clinical practice, INR control could be widely improved [4,5]. Different studies have tried to determine which factors may predict a poor INR control [6]. In our study, the history of labile INR (12.3% of patients) was largely the main factor associated with a poor INR control. Thus, whereas in those patients with prior labile INR, only 18–20% of patients achieved an adequate INR control, these figures increased to 62–66% in those without prior labile INR. It has been reported that patients with AF who achieve INR stabilization within 1 year are 10 times more likely to remain on warfarin [7]. Warfarin resistance due to different genetic polymorphisms has been associated with a poorer INR control [8]. It is likely that the best option in a patient with nonvalvular AF and a history of labile INR is to switch to a non-VKA oral anticoagulant. However, the main challenge remains to detect which patients are more likely to have labile INR before taking VKAs. Despite some studies have analyzed which factors may be associated with a poorer INR control [6], the fact is that all these conditions refer or are limited to the patients' characteristics. However, the information available regarding the attitude of physicians about INR control is very scarce [9]. In PAULA, the behavior of physicians was extensively analyzed. Our data showed that compared with the patients with an adequate INR control, in those subjects with a poor INR control, the visits to the primary care physician and nurse as well as the number of INR records were increased. However, in 6 months, only one more visit to the general practitioner and one more visit to the primary care nurse were performed. In addition, compared with patients with an adequate anticoagulation control, in those subjects with poor INR control, only 3 more determinations of INR levels were performed in 12 months. Moreover, only about 42% of physicians performed any modification of anticoagulant therapy in those patients with a poor INR control. Therefore, although more actions were taken to improve INR control, these were insufficient. Moreover, in those patients with a poor INR control, approximately one third of physicians considered that the patient had a good INR control. The physicians' perception has been shown to be one of the main reasons for not modifying treatment [10]. In conclusion, despite some actions were performed to improve the quality of anticoagulation, these were clearly insufficient. Since the physicians' perception has a key role on therapeutic inertia, efforts should be focused on emphasizing the importance of achieving INR targets. On the other hand, in patients with prior labile INR, trying to keep INR
http://dx.doi.org/10.1016/j.ejim.2016.01.016 0953-6205/© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Escobar C, et al, Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately c, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.01.016
e2
Letters to the Editor
Table 1 Total number of visits due to anticoagulation in the last 6 months, and physicians' therapeutic behavior according to INR control. Total number of visits due to anticoagulation in the last 6 months, according to INR control. Direct method
Rosendaal method
Poor INR control
Good INR control
p
Poor INR control
Good INR control
p
7.3 ± 5.8 10.4 ± 5.5 1.4 ± 2.5 0.4 ± 1.0
6.3 ± 5.2 9.1 ± 4.8 1.0 ± 1.9 0.2 ± 0.6
0.006 b0.001 0.003 0.0002
7.2 ± 5.8 10.4 ± 5.5 1.4 ± 2.5 0.4 ± 1.1
6.5 ± 5.3 9.3 ± 4.9 1.0 ± 1.9 0.2 ± 0.6
0.008 0.001 0.002 0.0001
13.0
b0.0001
43.2
13.9
b0.0001
Type of modification in those patients in whom any modification was performed⁎ Modification of dose (%) 77.8 52.6 Switch to another oral anticoagulant (%) 44.9 17.7 Referral to another specialist (%) 12.0 9.7
b0.0001 b0.0001 0.51
75.8 46.0 13.1
52.1 18.8 7.8
b0.0001 b0.0001 0.12
Primary care physician Primary care nurse Specialist Emergency department
Physicians' therapeutic behavior according to INR control Any modification performed by physicians (%) 41.7
⁎ More than one option could be done.
levels within recommended goals may not be the best option, but switching to a non-VKA oral anticoagulant. Learning points • In clinical practice, approximately 60% of patients achieved an adequate INR control. • In those patients with known prior labile INR, good anticoagulation control was achieved in less than 21% of patients. • Compared with patients with a good INR control, in patients with poor control, the number of visits to general practitioners and nurses was increased, more INR determinations were taken, and AVK dosage was more commonly modified. Despite that, many patients did not attain an adequate INR control. • In those patients with a poor INR control, approximately one third of physicians considered the patient had an adequate INR control.
Conflict of interests Authors have no conflict of interest to declare. References [1] Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369–429. [2] Mearns ES, White CM, Kohn CG, Hawthorne J, Song JS, Meng J, et al. Quality of vitamin K antagonist control and outcomes in atrial fibrillation patients: a meta-analysis and meta-regression. Thromb J 2014;12:14. [3] Lip GY, Rushton-Smith SK, Goldhaber SZ, Fitzmaurice DA, Mantovani LG, Goto S, et al. GARFIELD-AF investigators. Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation. Circ Cardiovasc Qual Outcomes 2015;8(2 Suppl 1):S12–20.
[4] Pokorney SD, Simon DN, Thomas L, Fonarow GC, Kowey PR, Chang P, et al. Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: results from ORBIT-AF registry. Am Heart J 2015;170:141–8. [5] Barrios V, Escobar C, Prieto L, Osorio G, Polo J, Lobos JM, et al. Anticoagulation control in patients with nonvalvular atrial fibrillation attended at primary care centers in Spain: the PAULA study. Rev Esp Cardiol 2015;68:769–76. [6] Roldán V, Cancio S, Gálvez J, Valdés M, Vicente V, Marín F, et al. The SAMe-TT2R2 score predicts poor anticoagulation control in AF patients: a prospective “realworld” inception cohort study. Am J Med 2015;128:1237–43. [7] Nelson WW, Desai S, Damaraju CV, Lu L, Fields LE, Wildgoose P, et al. International normalized ratio stabilization in newly initiated warfarin patients with nonvalvular atrial fibrillation. Curr Med Res Opin 2014;30:2437–42. [8] Oldenburg J, Müller CR, Rost S, Watzka M, Bevans CG. Comparative genetics of warfarin resistance. Hamostaseologie 2014;34:143–59. [9] Bahri O, Roca F, Lechani T, Druesne L, Jouanny P, Serot JM, et al. Underuse of oral anticoagulation for individuals with atrial fibrillation in a nursing home setting in France: comparisons of resident characteristics and physician attitude. J Am Geriatr Soc 2015;63:71–6. [10] Escobar C, Barrios V, Alonso-Moreno FJ, Prieto MA, Valls F, Calderon A, et al. Evolution of therapy inertia in primary care setting in Spain during 2002–2010. J Hypertens 2014;32:1138–45.
Carlos Escobar Cardiology Department, University Hospital La Paz, Madrid, Spain Corresponding author. E-mail address: [email protected]. Vivencio Barrios Cardiology Department, University Hospital Ramon y Cajal, Madrid, Spain Luis Prieto Medical Biostatistics, Universidad Católica San Antonio de Murcia, Murcia, Spain 11 January 2016 Available online xxxx
Please cite this article as: Escobar C, et al, Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately c, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.01.016
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letters to the Editor Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately controlled Keywords: Atrial fibrillation Vitamin K antagonist Therapeutic behavior Inertia
In the majority of patients with atrial fibrillation (AF), long-term oral anticoagulation is necessary to reduce the risk of stroke. Although effective, vitamin K antagonists (VKAs) exhibit many limitations [1,2]. Despite that, they are still widely used in clinical practice [3]. Maintaining the international normalized ratio (INR) of patients within the therapeutic range is crucial to reduce the risk of thromboembolic events with no marked increase on hemorrhagic complications [2]. Overall, it has been reported that around 35–50% of patients treated with VKAs have an inadequate INR control [4,5]. Different factors (i.e. polymedication, comorbidities, etc.) have been associated with this poor INR control [4,5]. However, little is known about the attitude of physicians when time in therapeutic range (TTR) is out of range. The aim of this study was to examine the therapeutic behavior of primary care physicians in patients taking VKAs not adequately controlled. PAULA was a cross-sectional/retrospective study, involving patients with nonvalvular AF attended in primary care setting in Spain, who had received treatment with VKAs for at least the last year [5]. The study was approved by the Clinical Research Ethics Committee of the University Hospital La Paz of Madrid. All patients signed the written informed consent before inclusion. The study involved a single visit that coincided with one of the patient's regular follow-up visits. Data were collected from the medical history and physician interview. To assess patients' INR control, the TTR in the past 12 months was calculated at a core lab by both the direct method (proportion of INR values within therapeutic range) and the Rosendaal method. Labile INR was considered when TTR b 60% [5]. A total of 1524 patients (mean age 77.4 ± 8.7 years; 48.6% women; 64.2% with permanent AF) were analyzed. The mean time from AF diagnosis to the study date was 6.0 ± 4.2 years and 12.3% of patients had a history of labile INR. Mean CHADS2 was 2.3 ± 1.2, CHA2DS2-VASc 3.9 ± 1.5 and HAS-BLED 1.6 ± 0.9. The percent TTR was 63.2 ± 17.9% and 69.0 ± 17.7% according to the direct and Rosendaal methods, respectively and a 56.9% and 60.6% of patients achieved an adequate INR control, respectively. In the last 6 months, the mean number of anticoagulation controlrelated visits to the primary care physician was 6.8 ± 5.5, to the primary care nurse 9.7 ± 5.2, to the specialist 1.1 ± 2.2 and to the emergency department 0.3 ± 0.9 (Table 1). The total number of INR readings recorded in the previous 12 months was 21,982 (15.9 ± 4.2 in those individuals with poor INR control vs 13.3 ± 3.1 in those with good INR control
[direct method]; p b 0.001; and 15.9 ± 4.3 vs 13.3 ± 3.1, respectively; p b 0.001 [Rosendaal method]). In 30.5% of the INR readings, the anticoagulant dose was modified (72.1% in case of INR out of range vs 3.7% in those patients with INR within range interval; p b 0.0001). Anticoagulant therapy was modified by 25.4% of physicians (59.9% modified the dosage of AVK; 37.0% switched to another oral anticoagulant; 11.4% referred to another specialist; and 3.1% performed other action (Table 1). In 65.0% of patients, the physician considered that the patient had a good INR control. The PAULA study included a broad sample of patients representative of the whole Spanish population with nonvalvular AF attended in primary care, with a high number of INR controls and a long follow-up period. In line with other studies, our data showed that in clinical practice, INR control could be widely improved [4,5]. Different studies have tried to determine which factors may predict a poor INR control [6]. In our study, the history of labile INR (12.3% of patients) was largely the main factor associated with a poor INR control. Thus, whereas in those patients with prior labile INR, only 18–20% of patients achieved an adequate INR control, these figures increased to 62–66% in those without prior labile INR. It has been reported that patients with AF who achieve INR stabilization within 1 year are 10 times more likely to remain on warfarin [7]. Warfarin resistance due to different genetic polymorphisms has been associated with a poorer INR control [8]. It is likely that the best option in a patient with nonvalvular AF and a history of labile INR is to switch to a non-VKA oral anticoagulant. However, the main challenge remains to detect which patients are more likely to have labile INR before taking VKAs. Despite some studies have analyzed which factors may be associated with a poorer INR control [6], the fact is that all these conditions refer or are limited to the patients' characteristics. However, the information available regarding the attitude of physicians about INR control is very scarce [9]. In PAULA, the behavior of physicians was extensively analyzed. Our data showed that compared with the patients with an adequate INR control, in those subjects with a poor INR control, the visits to the primary care physician and nurse as well as the number of INR records were increased. However, in 6 months, only one more visit to the general practitioner and one more visit to the primary care nurse were performed. In addition, compared with patients with an adequate anticoagulation control, in those subjects with poor INR control, only 3 more determinations of INR levels were performed in 12 months. Moreover, only about 42% of physicians performed any modification of anticoagulant therapy in those patients with a poor INR control. Therefore, although more actions were taken to improve INR control, these were insufficient. Moreover, in those patients with a poor INR control, approximately one third of physicians considered that the patient had a good INR control. The physicians' perception has been shown to be one of the main reasons for not modifying treatment [10]. In conclusion, despite some actions were performed to improve the quality of anticoagulation, these were clearly insufficient. Since the physicians' perception has a key role on therapeutic inertia, efforts should be focused on emphasizing the importance of achieving INR targets. On the other hand, in patients with prior labile INR, trying to keep INR
http://dx.doi.org/10.1016/j.ejim.2016.01.016 0953-6205/© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Escobar C, et al, Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately c, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.01.016
e2
Letters to the Editor
Table 1 Total number of visits due to anticoagulation in the last 6 months, and physicians' therapeutic behavior according to INR control. Total number of visits due to anticoagulation in the last 6 months, according to INR control. Direct method
Rosendaal method
Poor INR control
Good INR control
p
Poor INR control
Good INR control
p
7.3 ± 5.8 10.4 ± 5.5 1.4 ± 2.5 0.4 ± 1.0
6.3 ± 5.2 9.1 ± 4.8 1.0 ± 1.9 0.2 ± 0.6
0.006 b0.001 0.003 0.0002
7.2 ± 5.8 10.4 ± 5.5 1.4 ± 2.5 0.4 ± 1.1
6.5 ± 5.3 9.3 ± 4.9 1.0 ± 1.9 0.2 ± 0.6
0.008 0.001 0.002 0.0001
13.0
b0.0001
43.2
13.9
b0.0001
Type of modification in those patients in whom any modification was performed⁎ Modification of dose (%) 77.8 52.6 Switch to another oral anticoagulant (%) 44.9 17.7 Referral to another specialist (%) 12.0 9.7
b0.0001 b0.0001 0.51
75.8 46.0 13.1
52.1 18.8 7.8
b0.0001 b0.0001 0.12
Primary care physician Primary care nurse Specialist Emergency department
Physicians' therapeutic behavior according to INR control Any modification performed by physicians (%) 41.7
⁎ More than one option could be done.
levels within recommended goals may not be the best option, but switching to a non-VKA oral anticoagulant. Learning points • In clinical practice, approximately 60% of patients achieved an adequate INR control. • In those patients with known prior labile INR, good anticoagulation control was achieved in less than 21% of patients. • Compared with patients with a good INR control, in patients with poor control, the number of visits to general practitioners and nurses was increased, more INR determinations were taken, and AVK dosage was more commonly modified. Despite that, many patients did not attain an adequate INR control. • In those patients with a poor INR control, approximately one third of physicians considered the patient had an adequate INR control.
Conflict of interests Authors have no conflict of interest to declare. References [1] Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369–429. [2] Mearns ES, White CM, Kohn CG, Hawthorne J, Song JS, Meng J, et al. Quality of vitamin K antagonist control and outcomes in atrial fibrillation patients: a meta-analysis and meta-regression. Thromb J 2014;12:14. [3] Lip GY, Rushton-Smith SK, Goldhaber SZ, Fitzmaurice DA, Mantovani LG, Goto S, et al. GARFIELD-AF investigators. Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation. Circ Cardiovasc Qual Outcomes 2015;8(2 Suppl 1):S12–20.
[4] Pokorney SD, Simon DN, Thomas L, Fonarow GC, Kowey PR, Chang P, et al. Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: results from ORBIT-AF registry. Am Heart J 2015;170:141–8. [5] Barrios V, Escobar C, Prieto L, Osorio G, Polo J, Lobos JM, et al. Anticoagulation control in patients with nonvalvular atrial fibrillation attended at primary care centers in Spain: the PAULA study. Rev Esp Cardiol 2015;68:769–76. [6] Roldán V, Cancio S, Gálvez J, Valdés M, Vicente V, Marín F, et al. The SAMe-TT2R2 score predicts poor anticoagulation control in AF patients: a prospective “realworld” inception cohort study. Am J Med 2015;128:1237–43. [7] Nelson WW, Desai S, Damaraju CV, Lu L, Fields LE, Wildgoose P, et al. International normalized ratio stabilization in newly initiated warfarin patients with nonvalvular atrial fibrillation. Curr Med Res Opin 2014;30:2437–42. [8] Oldenburg J, Müller CR, Rost S, Watzka M, Bevans CG. Comparative genetics of warfarin resistance. Hamostaseologie 2014;34:143–59. [9] Bahri O, Roca F, Lechani T, Druesne L, Jouanny P, Serot JM, et al. Underuse of oral anticoagulation for individuals with atrial fibrillation in a nursing home setting in France: comparisons of resident characteristics and physician attitude. J Am Geriatr Soc 2015;63:71–6. [10] Escobar C, Barrios V, Alonso-Moreno FJ, Prieto MA, Valls F, Calderon A, et al. Evolution of therapy inertia in primary care setting in Spain during 2002–2010. J Hypertens 2014;32:1138–45.
Carlos Escobar Cardiology Department, University Hospital La Paz, Madrid, Spain Corresponding author. E-mail address: [email protected]. Vivencio Barrios Cardiology Department, University Hospital Ramon y Cajal, Madrid, Spain Luis Prieto Medical Biostatistics, Universidad Católica San Antonio de Murcia, Murcia, Spain 11 January 2016 Available online xxxx
Please cite this article as: Escobar C, et al, Therapeutic behavior of primary care physicians in patients with atrial fibrillation taking vitamin K antagonists not adequately c, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.01.016