indian heart journal 67 (2015) s1–s3
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Editorial
Stroke prevention in atrial fibrillation: Where are we now?§ Atrial fibrillation (AF) is the commonest cardiac arrhythmia and represents a global healthcare problem.1 The main priority in AF management is stroke prevention,2 and following this, having a patient-centered and symptom-directed approach to consider rate or rhythm control. Of course, given the association of AF with various comorbidities, attention to correction and/or treatment of risk factors such as hypertension, diabetes, and heart failure is part of the holistic approach to AF management. While the risk of stroke in AF is increased fivefold, this risk is not homogeneous and depends on the presence or absence of various stroke risk factors. The latter has been incorporated into stroke risk stratification scores, such as the CHADS2 and CHA2DS2-VASc scores.2 With regard to stroke prevention, all the major guidelines (European,3 American,4 and National Institute for Health and Care Excellence (NICE)5) now recommend use of the CHA2DS2-VASc score6 for stroke risk stratification. A simplified approach to stroke prevention is shown in Fig. 1.7 The initial focus on identification of 'truly low-risk' patients with AF [STEP 1], that is, those patients who are with a CHA2DS2-VASc score = 0 (male) or 1 (female) and those who do not need any antithrombotic therapy. Subsequent to this [STEP 2], patients with AF and ≥1 stroke risk factors can be offered effective stroke prevention, which is essentially oral anticoagulation. Oral anticoagulation is given either as a NonVitamin K Antagonist Oral Anticoagulant (NOAC) or as a Vitamin K Antagonist (VKA, e.g. warfarin) with good quality anticoagulation control as reflected by a time in therapeutic range (TTR) >70%. Use of the NOACs is supported by a strong evidence base from large well-conducted clinical trials. However, translating the evidence to everyday clinical practice is another matter.8 Also, some patient groups were not studied in the NOAC trials, and additional research is still required.9 For now, how best to manage such patients requires some expert consensus-based advice. Given the increasing use of NOACs, the Indian consensus guidance paper on stroke prevention in AF by Dalal et al. in
this issue of the Indian Heart Journal is very timely, particularly with its emphasis on practical use of NOACs. The latter drugs are relatively new, and thus, many clinicians have questions on how and when to use these drugs. Important practical approaches are highlighted and schemes to help everyday management are suggested. Indeed, the approaches are complementary to similar practical guides, such as the European Heart Rhythm practical guide on NOACs, which has recently been updated.10 Translating to clinical practice can sometimes raise questions on patient populations with less limited data. For example, some discussion is whether a single risk factor (e.g. CHA2DS2-VASc score = 1 in males, 2 in females) merits oral anticoagulation.11,12 Unsurprisingly, differences in stroke rates would be evident between stable community-based 'uncomplicated' outpatients and patients with a first-time AF diagnosis which is often discovered during an in-hospital stay, whether AF was the primary diagnosis or with AF secondary to other acute disease. Of note, recent data from Asia and Europe13,14 show ischemic stroke rates of 1.5–3%/year with a single stroke risk factor (i.e. CHA2DS2-VASc 1 in males, 2 in females). The net clinical benefit is also positive for OAC vs untreated or OAC vs aspirin; in contrast, the NCB is neutral/negative for aspirin vs untreated.15 Thus, clinicians need to ask themselves whether it is worth taking the risk of exposing such AF patients to fatal and disabling strokes. Indeed, AF patients are also not 'static' in relation to their risk profile, being elderly and having multiple comorbidities. Some healthcare systems also manage warfarin very well, and hence, a question often asked is how to identify those patients likely to do well on warfarin (with a high TTR, and hence, low rates of thromboembolism and bleeding16,17), rather than a blanket 'NOAC for everyone' policy or a 'trial of warfarin' approach which leaves patients with suboptimal anticoagulation control for the initial few months prior to a decision being taken about whether a
§ This editorial is pertaining to the article: The Indian Consensus Guidance on Stroke Prevention in Atrial Fibrillation: An Emphasis on Practical Use of Non-Vitamin K Oral Anticoagulants.
S2
indian heart journal 67 (2015) s1–s3
Fig. 1
NOAC can be prescribed.18 The SAMe-TT2R2 score19 has recently been introduced to help physicians make informed decisions on those patients likely to do well on warfarin (SAMe-TT2R2 score 0–2) or those where on probability are likely to have a poor TTR (SAMe-TT2R2 score >2). The latter group would benefit from more intense counseling, education, and follow-up, or preferentially, a NOAC.18,20,21 In conclusion, the NOACs are here to stay – but they are no longer new nor novel.22–24 These drugs work well, if used appropriately and correctly in the right patients.25 The Indian consensus document is a timely and valued addition to providing practical guidance on how best to use such drugs in a safe and appropriate manner. After all, prescribing label or guideline adherent treatment is associated with far improved outcomes in AF patients. Things can only get better.
Conflicts of interest Chairman, Scientific Documents Committee, European Heart Rhythm Association (EHRA). Reviewer for various guidelines and position statements from ESC, EHRA, NICE, etc. Steering Committees/trials: Includes steering committees for various Phase II and III studies, Health Economics & Outcomes Research, etc. Investigator in various clinical trials in cardiovascular disease, including those on antithrombotic therapies in AF, acute coronary syndrome, lipids, etc. Consultant for Bayer/Jensen J&J, Astellas, Merck, Sanofi, BMS/Pfizer, Biotronik, Medtronic, Portola, Boehringer Ingelheim, Microlife and Daiichi-Sankyo. Speaker for Bayer, BMS/ Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo.
references
1. Lip GY, Brechin CM, Lane DA. The global burden of atrial fibrillation and stroke: a systematic review of the epidemiology of atrial fibrillation in regions outside North America and Europe. Chest. 2012;142:1489–1498. 2. Lip GYH, Lane D. Stroke prevention in atrial fibrillation. A systematic review. JAMA. 2015;313:1950–1962. 3. Camm AJ, Lip GY, De Caterina R, et al. 2012 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 – developed with the special contribution of the European Heart Rhythm Association. Europace. 2012;14:1385–1413. 4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071–2104. 5. National-Institute-for-Health-and-Care-Excellence. Atrial fibrillation: the management of atrial fibrillation (Clinical guideline 180). 2014. http://guidance.nice.org.uk/CG180. 6. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. 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;138:1093–1100. 7. Lip GY, Lane DA. Modern management of atrial fibrillation requires initial identification of ‘‘low-risk’’ patients using the CHADS-VASc score, and not focusing on high-risk prediction. Circ J. 2014. 8. Hylek EM, Ko D, Cove CL. Gaps in translation from trials to practice: non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation. Thromb Haemost. 2014;111:783–788. 9. Hankey GJ. Unanswered questions and research priorities to optimise stroke prevention in atrial fibrillation with the
indian heart journal 67 (2015) s1–s3
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
new oral anticoagulants. Thromb Haemost. 2014;111: 808–816. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17: 1467–1507. Nielsen PB, Chao TF. The risks of risk scores for stroke risk assessment in atrial fibrillation. Thromb Haemost. 2015;113:1170–1173. Olesen JB, Torp-Pedersen C. Stroke risk in atrial fibrillation: do we anticoagulate CHADS2 or CHA2DS2-VASc >/= 1, or higher? Thromb Haemost. 2015;113:1165–1169. Chao TF, Liu CJ, Wang KL, et al. Should atrial fibrillation patients with 1 additional risk factor of the CHA2DS2-VASc score (beyond sex) receive oral anticoagulation. J Am Coll Cardiol. 2015;65:635–642. Lip GY, Skjoth F, Rasmussen LH, Larsen TB. Oral anticoagulation, aspirin, or no therapy in patients with nonvalvular AF with 0 or 1 stroke risk factor based on the CHADS-VASc score. J Am Coll Cardiol. 2015;65:1385–1394. Lip GY, Skjoth F, Nielsen PB, Larsen TB. Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA2DS2-VASc score. A comprehensive net clinical benefit analysis for warfarin, aspirin, or no therapy. Thromb Haemost. 2015;114:826–834. Sjogren V, Grzymala-Lubanski B, Renlund H, et al. Safety and efficacy of well managed warfarin. A report from the Swedish quality register Auricula. Thromb Haemost. 2015;113:1370–1377. Gallego P, Roldan V, Marin F, et al. Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation. Thromb Haemost. 2013;110:1189–1198. Fauchier L, Poli D, Olshansky B. The SAMe-TT2R2 score and quality of anticoagulation in AF: can we predict which patient benefits from anticoagulation. Thromb Haemost. 2015;114:657–659. Apostolakis S, Sullivan RM, Olshansky B, Lip GY. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: the SAMe-TT(2)R(2) score. Chest. 2013;144:1555–1563.
S3
20. Proietti M, Lip GY. Simple decision making between a vitamin k antagonist and non-vitamin K antagonist oral anticoagulant (NOACs): using the SAMe-TT2R2 score. Eur Heart J. 2015;1:150–152. 21. Ruiz-Ortiz M, Bertomeu V, Cequier A, Marin F, Anguita M. Validation of the SAMe-TT2R2 score in a nationwide population of nonvalvular atrial fibrillation patients on vitamin K antagonists. Thromb Haemost. 2015;114:. 22. Husted S, de Caterina R, Andreotti F, et al. Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel. Thromb Haemost. 2014;111:781–782. 23. Husted S, Lip GY, on behalf of the ESCWGoTTFoAiHD. Response to Ansell et al. ‘‘Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel’’ (Thromb Haemost 2014; dx.doi.org/10.1160/TH14-04-0325). Thromb Haemost. 2014;112:. 24. De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;110:1087–1107. 25. Lip GY, Clemens A, Noack H, Ferreira J, Connolly SJ, Yusuf S. Patient outcomes using the European label for dabigatran. A post-hoc analysis from the RELY database. Thromb Haemost. 2014;111:933–942.
Gregory Y.H. Lip MD, FRCP, FESC, FACCa,b University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, England, United Kingdom b Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark E-mail address: [email protected] a
Available online 28 November 2015 http://dx.doi.org/10.1016/j.ihj.2015.11.002 0019-4832/ # 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ihj
Editorial
Stroke prevention in atrial fibrillation: Where are we now?§ Atrial fibrillation (AF) is the commonest cardiac arrhythmia and represents a global healthcare problem.1 The main priority in AF management is stroke prevention,2 and following this, having a patient-centered and symptom-directed approach to consider rate or rhythm control. Of course, given the association of AF with various comorbidities, attention to correction and/or treatment of risk factors such as hypertension, diabetes, and heart failure is part of the holistic approach to AF management. While the risk of stroke in AF is increased fivefold, this risk is not homogeneous and depends on the presence or absence of various stroke risk factors. The latter has been incorporated into stroke risk stratification scores, such as the CHADS2 and CHA2DS2-VASc scores.2 With regard to stroke prevention, all the major guidelines (European,3 American,4 and National Institute for Health and Care Excellence (NICE)5) now recommend use of the CHA2DS2-VASc score6 for stroke risk stratification. A simplified approach to stroke prevention is shown in Fig. 1.7 The initial focus on identification of 'truly low-risk' patients with AF [STEP 1], that is, those patients who are with a CHA2DS2-VASc score = 0 (male) or 1 (female) and those who do not need any antithrombotic therapy. Subsequent to this [STEP 2], patients with AF and ≥1 stroke risk factors can be offered effective stroke prevention, which is essentially oral anticoagulation. Oral anticoagulation is given either as a NonVitamin K Antagonist Oral Anticoagulant (NOAC) or as a Vitamin K Antagonist (VKA, e.g. warfarin) with good quality anticoagulation control as reflected by a time in therapeutic range (TTR) >70%. Use of the NOACs is supported by a strong evidence base from large well-conducted clinical trials. However, translating the evidence to everyday clinical practice is another matter.8 Also, some patient groups were not studied in the NOAC trials, and additional research is still required.9 For now, how best to manage such patients requires some expert consensus-based advice. Given the increasing use of NOACs, the Indian consensus guidance paper on stroke prevention in AF by Dalal et al. in
this issue of the Indian Heart Journal is very timely, particularly with its emphasis on practical use of NOACs. The latter drugs are relatively new, and thus, many clinicians have questions on how and when to use these drugs. Important practical approaches are highlighted and schemes to help everyday management are suggested. Indeed, the approaches are complementary to similar practical guides, such as the European Heart Rhythm practical guide on NOACs, which has recently been updated.10 Translating to clinical practice can sometimes raise questions on patient populations with less limited data. For example, some discussion is whether a single risk factor (e.g. CHA2DS2-VASc score = 1 in males, 2 in females) merits oral anticoagulation.11,12 Unsurprisingly, differences in stroke rates would be evident between stable community-based 'uncomplicated' outpatients and patients with a first-time AF diagnosis which is often discovered during an in-hospital stay, whether AF was the primary diagnosis or with AF secondary to other acute disease. Of note, recent data from Asia and Europe13,14 show ischemic stroke rates of 1.5–3%/year with a single stroke risk factor (i.e. CHA2DS2-VASc 1 in males, 2 in females). The net clinical benefit is also positive for OAC vs untreated or OAC vs aspirin; in contrast, the NCB is neutral/negative for aspirin vs untreated.15 Thus, clinicians need to ask themselves whether it is worth taking the risk of exposing such AF patients to fatal and disabling strokes. Indeed, AF patients are also not 'static' in relation to their risk profile, being elderly and having multiple comorbidities. Some healthcare systems also manage warfarin very well, and hence, a question often asked is how to identify those patients likely to do well on warfarin (with a high TTR, and hence, low rates of thromboembolism and bleeding16,17), rather than a blanket 'NOAC for everyone' policy or a 'trial of warfarin' approach which leaves patients with suboptimal anticoagulation control for the initial few months prior to a decision being taken about whether a
§ This editorial is pertaining to the article: The Indian Consensus Guidance on Stroke Prevention in Atrial Fibrillation: An Emphasis on Practical Use of Non-Vitamin K Oral Anticoagulants.
S2
indian heart journal 67 (2015) s1–s3
Fig. 1
NOAC can be prescribed.18 The SAMe-TT2R2 score19 has recently been introduced to help physicians make informed decisions on those patients likely to do well on warfarin (SAMe-TT2R2 score 0–2) or those where on probability are likely to have a poor TTR (SAMe-TT2R2 score >2). The latter group would benefit from more intense counseling, education, and follow-up, or preferentially, a NOAC.18,20,21 In conclusion, the NOACs are here to stay – but they are no longer new nor novel.22–24 These drugs work well, if used appropriately and correctly in the right patients.25 The Indian consensus document is a timely and valued addition to providing practical guidance on how best to use such drugs in a safe and appropriate manner. After all, prescribing label or guideline adherent treatment is associated with far improved outcomes in AF patients. Things can only get better.
Conflicts of interest Chairman, Scientific Documents Committee, European Heart Rhythm Association (EHRA). Reviewer for various guidelines and position statements from ESC, EHRA, NICE, etc. Steering Committees/trials: Includes steering committees for various Phase II and III studies, Health Economics & Outcomes Research, etc. Investigator in various clinical trials in cardiovascular disease, including those on antithrombotic therapies in AF, acute coronary syndrome, lipids, etc. Consultant for Bayer/Jensen J&J, Astellas, Merck, Sanofi, BMS/Pfizer, Biotronik, Medtronic, Portola, Boehringer Ingelheim, Microlife and Daiichi-Sankyo. Speaker for Bayer, BMS/ Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo.
references
1. Lip GY, Brechin CM, Lane DA. The global burden of atrial fibrillation and stroke: a systematic review of the epidemiology of atrial fibrillation in regions outside North America and Europe. Chest. 2012;142:1489–1498. 2. Lip GYH, Lane D. Stroke prevention in atrial fibrillation. A systematic review. JAMA. 2015;313:1950–1962. 3. Camm AJ, Lip GY, De Caterina R, et al. 2012 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 – developed with the special contribution of the European Heart Rhythm Association. Europace. 2012;14:1385–1413. 4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071–2104. 5. National-Institute-for-Health-and-Care-Excellence. Atrial fibrillation: the management of atrial fibrillation (Clinical guideline 180). 2014. http://guidance.nice.org.uk/CG180. 6. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. 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;138:1093–1100. 7. Lip GY, Lane DA. Modern management of atrial fibrillation requires initial identification of ‘‘low-risk’’ patients using the CHADS-VASc score, and not focusing on high-risk prediction. Circ J. 2014. 8. Hylek EM, Ko D, Cove CL. Gaps in translation from trials to practice: non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation. Thromb Haemost. 2014;111:783–788. 9. Hankey GJ. Unanswered questions and research priorities to optimise stroke prevention in atrial fibrillation with the
indian heart journal 67 (2015) s1–s3
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
new oral anticoagulants. Thromb Haemost. 2014;111: 808–816. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17: 1467–1507. Nielsen PB, Chao TF. The risks of risk scores for stroke risk assessment in atrial fibrillation. Thromb Haemost. 2015;113:1170–1173. Olesen JB, Torp-Pedersen C. Stroke risk in atrial fibrillation: do we anticoagulate CHADS2 or CHA2DS2-VASc >/= 1, or higher? Thromb Haemost. 2015;113:1165–1169. Chao TF, Liu CJ, Wang KL, et al. Should atrial fibrillation patients with 1 additional risk factor of the CHA2DS2-VASc score (beyond sex) receive oral anticoagulation. J Am Coll Cardiol. 2015;65:635–642. Lip GY, Skjoth F, Rasmussen LH, Larsen TB. Oral anticoagulation, aspirin, or no therapy in patients with nonvalvular AF with 0 or 1 stroke risk factor based on the CHADS-VASc score. J Am Coll Cardiol. 2015;65:1385–1394. Lip GY, Skjoth F, Nielsen PB, Larsen TB. Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA2DS2-VASc score. A comprehensive net clinical benefit analysis for warfarin, aspirin, or no therapy. Thromb Haemost. 2015;114:826–834. Sjogren V, Grzymala-Lubanski B, Renlund H, et al. Safety and efficacy of well managed warfarin. A report from the Swedish quality register Auricula. Thromb Haemost. 2015;113:1370–1377. Gallego P, Roldan V, Marin F, et al. Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation. Thromb Haemost. 2013;110:1189–1198. Fauchier L, Poli D, Olshansky B. The SAMe-TT2R2 score and quality of anticoagulation in AF: can we predict which patient benefits from anticoagulation. Thromb Haemost. 2015;114:657–659. Apostolakis S, Sullivan RM, Olshansky B, Lip GY. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: the SAMe-TT(2)R(2) score. Chest. 2013;144:1555–1563.
S3
20. Proietti M, Lip GY. Simple decision making between a vitamin k antagonist and non-vitamin K antagonist oral anticoagulant (NOACs): using the SAMe-TT2R2 score. Eur Heart J. 2015;1:150–152. 21. Ruiz-Ortiz M, Bertomeu V, Cequier A, Marin F, Anguita M. Validation of the SAMe-TT2R2 score in a nationwide population of nonvalvular atrial fibrillation patients on vitamin K antagonists. Thromb Haemost. 2015;114:. 22. Husted S, de Caterina R, Andreotti F, et al. Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel. Thromb Haemost. 2014;111:781–782. 23. Husted S, Lip GY, on behalf of the ESCWGoTTFoAiHD. Response to Ansell et al. ‘‘Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel’’ (Thromb Haemost 2014; dx.doi.org/10.1160/TH14-04-0325). Thromb Haemost. 2014;112:. 24. De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;110:1087–1107. 25. Lip GY, Clemens A, Noack H, Ferreira J, Connolly SJ, Yusuf S. Patient outcomes using the European label for dabigatran. A post-hoc analysis from the RELY database. Thromb Haemost. 2014;111:933–942.
Gregory Y.H. Lip MD, FRCP, FESC, FACCa,b University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, England, United Kingdom b Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark E-mail address: [email protected] a
Available online 28 November 2015 http://dx.doi.org/10.1016/j.ihj.2015.11.002 0019-4832/ # 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.
