International Journal of Cardiology 187 (2015) 683–685
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Management of stroke prevention in Bulgarian patients with non-valvular atrial fibrillation (BUL-AF Survey) Nikolay Margaritov Runev a,⁎,1, Stamen Mitev Dimitrov b,1 a b
Clinic of Cardiology, Department of Internal Diseases “Kirkovich”, University Alexandrovska Hospital, Sofia, Bulgaria Medical Department, Boehringer Ingelheim RCV GmbH and Co KG, Bulgarian Branch, Bulgaria
a r t i c l e
i n f o
Article history: Received 27 March 2015 Accepted 28 March 2015 Available online 31 March 2015 Keywords: Non-valvular atrial fibrillation Stroke prevention Dabigatran
It is well known that patients with atrial fibrillation (AF) have a 5-fold increased risk of stroke compared to those without AF [1]. Moreover, the incidence of ischemic stroke in asymptomatic or recurrent paroxysmal AF is comparable to this one in chronic AF. In this setting, the knowledge of the physicians about the anticoagulation therapy in AF is essential to reduce the AF complications and to improve the quality of patients' life. The current paper reports the results of BUL-AF Survey, which is a descriptive, multicenter, non-interventional, cross-sectional study, aimed to investigate the management of stroke prevention in Bulgarian patients with non-valvular AF (NVAF). A total of 350 cardiologists from outpatient clinics and district hospitals with expertise in anticoagulation of AF patients were involved. They were randomized about the size of their AF practice (small: ≤ 10% AF patient cases, seen per week; average: 11–25% and large: ≥ 26% AF patient cases). The physicians were asked to complete within a period of 180 days two questionnaires, concerning their opinion and judgment of the daily clinical practice. The main topics of interest included: awareness of AF Guidelines on stroke prevention [2]; first choice of the antithrombotic therapy; estimated share of AF patients on NOAC (at the time of the survey the direct thrombin inhibitor/DTI/Dabigatran was the only
⁎ Corresponding author at: University Alexandrovska Hospital, Department of Internal Diseases “Kirkovich”, Clinic of Cardiology, 1, St Georgi Sofiiski str., 1431 Sofia, Bulgaria. E-mail addresses: [email protected] (N.M. Runev), [email protected] (S.M. Dimitrov). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2015.03.420 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
registered NOAC in Bulgaria), on acetylsalicylic acid (ASA) or on a combination of vitamin K antagonists (VKA) or DTI + ASA; and barriers for anticoagulation treatment of AF patients. In these questionnaires the cardiologists did not record any details derived of a particular subject, but aggregate data of the patients, documented anonymously. Analysis of the questionnaires was based on the total non-missing data. A descriptive analysis was used for quantitative variables, as well as frequency and percentage analysis for qualitative variables. As a level of statistical significance was considered p b 0.05. The results of BUL-AF Survey provide important data for an assessment of AF management into the real life clinical practice of Bulgarian cardiologists. VKA was reported to be a first choice of treatment: in case of valvular AF (by 92% of the physicians); in patients on VKA and good INR control (by 85%) and when renal impairment was detected (by 55%). DTI Dabigatran was preferred as a first choice of therapy in cases of: inability to control INR within a therapeutic range when on VKA (by 95% of the cardiologists); major difficulty of access to INR test and control (by 92%) and thromboembolic or bleeding events despite of good INR control when on VKA (by 86%) (Fig. 1). The only benefit of VKA over DTI that was pointed out by 93% of the physicians was the price of the drug. The majority of the cardiologists, involved into the survey (77%), took examination of up to 100 patients per week (about 86 on average). Slightly less than 20% of them had AF. Among the AF patients, seen per week, the average share of the subjects on NOAC (DTI) was higher (27%, Fig. 2) than this one, obtained in ESC Pilot General Registry as a part of EuroObservational Research Programme — AF (8.4%) [3]. However, the average percentage of patients on ASA treatment (examined per week) was found to be also high (30%), which raised questions about the proportion of AF subjects with an indication for OAC according to the Guidelines, but not on anticoagulant treatment. The results of AFNET Registry showed a similar share (28.4%) of patients, eligible for, but not receiving OAC [4]. Moreover, in this Registry 16.9% of patients, indicated for OAC, were actually on antiplatelet drugs, whereas 11.2% of eligible ones did not take any antithrombotic therapy. The data of BUL-AF Survey were also comparable to the results of Euro Heart Survey (24% of cases, eligible for OAC, received antiplatelet drug) [5] and Realise-AF Registry (28.3% of patients with CHADS2 ≥ 2 were on antiplatelet treatment) [6]. These real world data highlight again that the anticoagulant therapy is highly dependent of the
684
N.M. Runev, S.M. Dimitrov / International Journal of Cardiology 187 (2015) 683–685
Fig. 1. First choice in the antithrombotic therapy: VKA vs DTI (% of physicians). VKA: Vitamin K antagonists. DTI: Direct thrombin inhibitor.
individual patient's peculiarities: age, comorbidities, adherence to therapy, and personal preferences. A combination VKA or DTI + ASA was used by 22% of the cardiologists, involved into the survey, mainly with small AF practices. In ORBIT-AF Registry the prevalence of the combined therapy OAC + ASA was even higher (35%), despite of the fact that 17% of these patients had elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding risk score [7,8]. The results of post-hoc analysis of the RELY trial clearly demonstrated that the concomitant use of antiplatelet therapy increases
the risk of major bleeding with comparable effects seen for Dabigatran 110 mg bid, 150 mg bid or Warfarin [9,10]. Thus, the cardiologists should carefully determine if the benefits of concomitant ASA outweigh the risk in patients, already on VKA or DTI. In this setting, the vast majority of the physicians in the survey (97%) seemed to be aware of the significantly elevated bleeding risk when nonsteroidal anti-inflammatory drugs were added to OAC. On the other side, in BUL-AF survey as the most important barriers for anticoagulant treatment were reported: the patients' decision (by
Fig. 2. Treatment of patients with atrial fibrillation went through per week: NOAC vs ASA. NOAC: New oral anticoagulants. ASA: Acetylsalicylic acid.
N.M. Runev, S.M. Dimitrov / International Journal of Cardiology 187 (2015) 683–685
44% of the physicians), the age (by 28% of them, despite of the well established net benefit of OAC/NOAC in the elderly) and the high risk of bleeding (by 25% of the cardiologists). These results reveal the physicians' concern of potential occurrence of serious adverse events, mainly hemorrhage. The data of ORBIT-AF Registry also pointed out this consideration: patients on Dabigatran had lower ATRIA bleeding risk score (mean 2.4 versus 2.8 in these ones on Warfarin, p b 0.0001) [11]. The following limitations of this study could be noted: only cardiologists of Outpatient clinics or District hospitals were involved, i.e., the physicians from University hospitals, as well as internists and general practitioners were significantly underrepresented. In this survey no details for individual AF patients (risk scores, additional treatment, comorbidities) were recorded, which has to be taken into account when extrapolating these data to the general population. In conclusion, the continuous medical education of the physicians is crucial for a better AF patients management according to their individual risk profile. Conflicts of interest Nikolay Runev has received research contracts and honoraria for lectures from Boehringer Ingelheim. Stamen Dimitrov is a full employee of Boehringer Ingelheim. References [1] M. Leonardi, J. Bissett, Prevention of atrial fibrillation, Curr. Opin. Cardiol. 20 (2005) 417–423.
685
[2] A.J. Camm, G.Y.H. Lip, R. De Caterina, et al., focused update of the ESC Guidelines for the management of atrial fibrillation. An update of the 2010 ESC Guidelines for the management of atrial fibrillation, Eur. Heart J. 33 (21) (2012) 2719–2747. [3] G.Y.H. Lip, C. Laroche, G.A. Dan, et al., A prospective survey in ESC member countries of AFib management: baseline results of EuroObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry, Europace 16 (3) (2014) 309–319. [4] M. Nabauer, A. Gerth, T. Limbourg, et al., The Registry of the German Competence NETwork on Atrial Fibrillation: patient characteristics and initial management, Europace 11 (4) (2009) 423–434. [5] R. Nieuwlaat, A. Capucci, A.J. Camm, et al., Atrial fibrillation management: a prospective survey in ESC Member Countries. The Euro Heart Survey on Atrial Fibrillation, Eur. Heart J. 26 (2005) 2422–2434. [6] M. Alam, S.J. Bandeali, S.A. Shahzad, N. Lakkis, Real-life global survey evaluating patients with atrial fibrillation (REALISE-AF): results of an international observational registry, Expert. Rev. Cardiovasc. Ther. 10 (3) (2012) 283–291. [7] J.P. Piccini, E.S. Fraulo, J.E. Ansell, et al., Outcomes registry for better informed treatment of atrial fibrillation: rationale and design of ORBIT-AF, Am. Heart J. 162 (4) (2011) 606–612. [8] B.A. Steinberg, S. Kim, J.P. Piccini, et al., Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry, Circulation 128 (7) (2013) 721–728. [9] J.W. Eikelboom, L. Wallentin, S.J. Connolly, 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 long-term anticoagulant therapy (RE-LY) trial, Circulation 123 (21) (2011) 2363–2372. [10] A.L. Dans, S.J. Connolly, L. Wallentin, et al., Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, Circulation 127 (5) (2013) 634–640. [11] B.A. Steinberg, D.N. Holmes, J.P. Piccini, et al., Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation, J. Am. Heart Assoc. 2 (6) (2013) e000535.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Management of stroke prevention in Bulgarian patients with non-valvular atrial fibrillation (BUL-AF Survey) Nikolay Margaritov Runev a,⁎,1, Stamen Mitev Dimitrov b,1 a b
Clinic of Cardiology, Department of Internal Diseases “Kirkovich”, University Alexandrovska Hospital, Sofia, Bulgaria Medical Department, Boehringer Ingelheim RCV GmbH and Co KG, Bulgarian Branch, Bulgaria
a r t i c l e
i n f o
Article history: Received 27 March 2015 Accepted 28 March 2015 Available online 31 March 2015 Keywords: Non-valvular atrial fibrillation Stroke prevention Dabigatran
It is well known that patients with atrial fibrillation (AF) have a 5-fold increased risk of stroke compared to those without AF [1]. Moreover, the incidence of ischemic stroke in asymptomatic or recurrent paroxysmal AF is comparable to this one in chronic AF. In this setting, the knowledge of the physicians about the anticoagulation therapy in AF is essential to reduce the AF complications and to improve the quality of patients' life. The current paper reports the results of BUL-AF Survey, which is a descriptive, multicenter, non-interventional, cross-sectional study, aimed to investigate the management of stroke prevention in Bulgarian patients with non-valvular AF (NVAF). A total of 350 cardiologists from outpatient clinics and district hospitals with expertise in anticoagulation of AF patients were involved. They were randomized about the size of their AF practice (small: ≤ 10% AF patient cases, seen per week; average: 11–25% and large: ≥ 26% AF patient cases). The physicians were asked to complete within a period of 180 days two questionnaires, concerning their opinion and judgment of the daily clinical practice. The main topics of interest included: awareness of AF Guidelines on stroke prevention [2]; first choice of the antithrombotic therapy; estimated share of AF patients on NOAC (at the time of the survey the direct thrombin inhibitor/DTI/Dabigatran was the only
⁎ Corresponding author at: University Alexandrovska Hospital, Department of Internal Diseases “Kirkovich”, Clinic of Cardiology, 1, St Georgi Sofiiski str., 1431 Sofia, Bulgaria. E-mail addresses: [email protected] (N.M. Runev), [email protected] (S.M. Dimitrov). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
http://dx.doi.org/10.1016/j.ijcard.2015.03.420 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
registered NOAC in Bulgaria), on acetylsalicylic acid (ASA) or on a combination of vitamin K antagonists (VKA) or DTI + ASA; and barriers for anticoagulation treatment of AF patients. In these questionnaires the cardiologists did not record any details derived of a particular subject, but aggregate data of the patients, documented anonymously. Analysis of the questionnaires was based on the total non-missing data. A descriptive analysis was used for quantitative variables, as well as frequency and percentage analysis for qualitative variables. As a level of statistical significance was considered p b 0.05. The results of BUL-AF Survey provide important data for an assessment of AF management into the real life clinical practice of Bulgarian cardiologists. VKA was reported to be a first choice of treatment: in case of valvular AF (by 92% of the physicians); in patients on VKA and good INR control (by 85%) and when renal impairment was detected (by 55%). DTI Dabigatran was preferred as a first choice of therapy in cases of: inability to control INR within a therapeutic range when on VKA (by 95% of the cardiologists); major difficulty of access to INR test and control (by 92%) and thromboembolic or bleeding events despite of good INR control when on VKA (by 86%) (Fig. 1). The only benefit of VKA over DTI that was pointed out by 93% of the physicians was the price of the drug. The majority of the cardiologists, involved into the survey (77%), took examination of up to 100 patients per week (about 86 on average). Slightly less than 20% of them had AF. Among the AF patients, seen per week, the average share of the subjects on NOAC (DTI) was higher (27%, Fig. 2) than this one, obtained in ESC Pilot General Registry as a part of EuroObservational Research Programme — AF (8.4%) [3]. However, the average percentage of patients on ASA treatment (examined per week) was found to be also high (30%), which raised questions about the proportion of AF subjects with an indication for OAC according to the Guidelines, but not on anticoagulant treatment. The results of AFNET Registry showed a similar share (28.4%) of patients, eligible for, but not receiving OAC [4]. Moreover, in this Registry 16.9% of patients, indicated for OAC, were actually on antiplatelet drugs, whereas 11.2% of eligible ones did not take any antithrombotic therapy. The data of BUL-AF Survey were also comparable to the results of Euro Heart Survey (24% of cases, eligible for OAC, received antiplatelet drug) [5] and Realise-AF Registry (28.3% of patients with CHADS2 ≥ 2 were on antiplatelet treatment) [6]. These real world data highlight again that the anticoagulant therapy is highly dependent of the
684
N.M. Runev, S.M. Dimitrov / International Journal of Cardiology 187 (2015) 683–685
Fig. 1. First choice in the antithrombotic therapy: VKA vs DTI (% of physicians). VKA: Vitamin K antagonists. DTI: Direct thrombin inhibitor.
individual patient's peculiarities: age, comorbidities, adherence to therapy, and personal preferences. A combination VKA or DTI + ASA was used by 22% of the cardiologists, involved into the survey, mainly with small AF practices. In ORBIT-AF Registry the prevalence of the combined therapy OAC + ASA was even higher (35%), despite of the fact that 17% of these patients had elevated Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding risk score [7,8]. The results of post-hoc analysis of the RELY trial clearly demonstrated that the concomitant use of antiplatelet therapy increases
the risk of major bleeding with comparable effects seen for Dabigatran 110 mg bid, 150 mg bid or Warfarin [9,10]. Thus, the cardiologists should carefully determine if the benefits of concomitant ASA outweigh the risk in patients, already on VKA or DTI. In this setting, the vast majority of the physicians in the survey (97%) seemed to be aware of the significantly elevated bleeding risk when nonsteroidal anti-inflammatory drugs were added to OAC. On the other side, in BUL-AF survey as the most important barriers for anticoagulant treatment were reported: the patients' decision (by
Fig. 2. Treatment of patients with atrial fibrillation went through per week: NOAC vs ASA. NOAC: New oral anticoagulants. ASA: Acetylsalicylic acid.
N.M. Runev, S.M. Dimitrov / International Journal of Cardiology 187 (2015) 683–685
44% of the physicians), the age (by 28% of them, despite of the well established net benefit of OAC/NOAC in the elderly) and the high risk of bleeding (by 25% of the cardiologists). These results reveal the physicians' concern of potential occurrence of serious adverse events, mainly hemorrhage. The data of ORBIT-AF Registry also pointed out this consideration: patients on Dabigatran had lower ATRIA bleeding risk score (mean 2.4 versus 2.8 in these ones on Warfarin, p b 0.0001) [11]. The following limitations of this study could be noted: only cardiologists of Outpatient clinics or District hospitals were involved, i.e., the physicians from University hospitals, as well as internists and general practitioners were significantly underrepresented. In this survey no details for individual AF patients (risk scores, additional treatment, comorbidities) were recorded, which has to be taken into account when extrapolating these data to the general population. In conclusion, the continuous medical education of the physicians is crucial for a better AF patients management according to their individual risk profile. Conflicts of interest Nikolay Runev has received research contracts and honoraria for lectures from Boehringer Ingelheim. Stamen Dimitrov is a full employee of Boehringer Ingelheim. References [1] M. Leonardi, J. Bissett, Prevention of atrial fibrillation, Curr. Opin. Cardiol. 20 (2005) 417–423.
685
[2] A.J. Camm, G.Y.H. Lip, R. De Caterina, et al., focused update of the ESC Guidelines for the management of atrial fibrillation. An update of the 2010 ESC Guidelines for the management of atrial fibrillation, Eur. Heart J. 33 (21) (2012) 2719–2747. [3] G.Y.H. Lip, C. Laroche, G.A. Dan, et al., A prospective survey in ESC member countries of AFib management: baseline results of EuroObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry, Europace 16 (3) (2014) 309–319. [4] M. Nabauer, A. Gerth, T. Limbourg, et al., The Registry of the German Competence NETwork on Atrial Fibrillation: patient characteristics and initial management, Europace 11 (4) (2009) 423–434. [5] R. Nieuwlaat, A. Capucci, A.J. Camm, et al., Atrial fibrillation management: a prospective survey in ESC Member Countries. The Euro Heart Survey on Atrial Fibrillation, Eur. Heart J. 26 (2005) 2422–2434. [6] M. Alam, S.J. Bandeali, S.A. Shahzad, N. Lakkis, Real-life global survey evaluating patients with atrial fibrillation (REALISE-AF): results of an international observational registry, Expert. Rev. Cardiovasc. Ther. 10 (3) (2012) 283–291. [7] J.P. Piccini, E.S. Fraulo, J.E. Ansell, et al., Outcomes registry for better informed treatment of atrial fibrillation: rationale and design of ORBIT-AF, Am. Heart J. 162 (4) (2011) 606–612. [8] B.A. Steinberg, S. Kim, J.P. Piccini, et al., Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry, Circulation 128 (7) (2013) 721–728. [9] J.W. Eikelboom, L. Wallentin, S.J. Connolly, 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 long-term anticoagulant therapy (RE-LY) trial, Circulation 123 (21) (2011) 2363–2372. [10] A.L. Dans, S.J. Connolly, L. Wallentin, et al., Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, Circulation 127 (5) (2013) 634–640. [11] B.A. Steinberg, D.N. Holmes, J.P. Piccini, et al., Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation, J. Am. Heart Assoc. 2 (6) (2013) e000535.
