Perspectives
Replacing warfarin for better or worse: patient factors and future directions Care models must consider patient factors to ensure safe and effective use of patient-administered anticoagulants
I
n Australia, atrial fibrillation (AF) affects 1%–2% of the population, placing them at a fivefold increased risk of stroke.1 The prevalence of AF increases sharply with age, with 50% of patients aged 75 years or over.2 Warfarin has been used clinically for more than 70 years and is the mainstay anticoagulant for prophylaxis of stroke as well as for the management of AF. However, in recent years, the novel oral anticoagulants (NOACs) dabigatran, rivaroxaban and apixaban have been developed. These promise more efficacy than warfarin in stroke prevention, while being safer and easier to use.3 A recent review by the Australian Government Department of Health and Ageing provided perspectives on current and future options for improving the use of anticoagulation therapies in managing patients with AF.2 In this article, we focus on strategies to improve anticoagulation management in patients with AF in light of the increasing utility of NOACs.
Warfarin in clinical practice Despite the availability of oral alternative therapies, warfarin — a vitamin K antagonist — remains efficacious and cost-effective in reducing the incidence of stroke in patients with AF.4 However, warfarin has a narrow therapeutic window, resulting in an unpredictable anticoagulant effect that necessitates frequent monitoring and dosage adjustment.4 Further, warfarin is associated with the clinical trade-off between the risk of ischaemic stroke and an increased risk of bleeding, particularly intracranial haemorrhage. As a consequence, a range of risk factors that can influence warfarin stability have been identified and are well known in clinical practice.5,6 These complexities have resulted in underuse of warfarin, particularly among older people, where the risk of cerebrovascular and cardiovascular events is highest.7 Although warfarin has been used clinically for many decades, there is an ongoing need to improve the monitoring and management of patients who receive it. Optimisation of time in the therapeutic range (TTR) is the key to improving patient outcomes. This requires identification of factors that can influence TTR and the incorporation of management strategies.2 Although multiple comorbidities and concomitant medications are regularly cited as reasons for poor TTR, other relevant patient factors, such as cognitive impairment and inadequate health literacy, should be considered, as these have been shown to influence anticoagulation control.8 156
MJA 199 (3) · 5 August 2013
Basia O Diug BBioMedSci(Hons), Lecturer and Research Fellow1
Judy A Lowthian PhD, MPH, BAppSc(SpPath), Senior Research Fellow1
Michael Dooley BPharm, GradDipHospPharm, Director of Pharmacy and Professor of Clinical Pharmacy2
1 School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC. 2 Alfred Hospital, Melbourne, VIC.
basia.diug@ monash.edu
doi: 10.5694/mja12.11863
Clinical trials of the new anticoagulants Dabigatran, a thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, are the fi rst oral alternatives to warfarin to be made available for the prevention of stroke and systemic embolism in patients with non-valvular AF. All three NOACs have demonstrated effectiveness in multinational randomised clinical trials although, to date, no studies have directly compared them. Pivotal trials for dabigatran (RELY),9 rivaroxaban (ROCKET AF)10,11 and apixaban (ARISTOTLE)12 recruited patients from 40 different countries, with the aim of evaluating their respective efficacy for the prevention of stroke and the risk of haemorrhage compared with warfarin (Box). The results look promising, with all three NOACs demonstrating non-inferiority to warfarin for stroke and systemic embolism prevention.9-12 However, their most consistent clinical benefit is that they are superior to warfarin when it comes to the rate of intracerebral haemorrhage and haemorrhagic stroke.10,12 Further, they have the notable practical advantages of involving fi xed dosages and not requiring international normalised ratio monitoring.3 Although these results show clear benefits, there are some significant differences between the trials, including different defi nitions at end points such as major bleeding, differences in follow-up periods, and different distribution of patients in various countries, making direct comparison difficult.13,14 Most notably, consideration must be given to the quality of warfarin management and stability in the control arms, as this varies markedly and is also at variance with that seen in clinical practice. The mean TTRs for patients taking warfarin in the three NOAC trials9-11 were 64%, 55% and 62%, respectively. These proportions are significantly lower than that found in the Australian population, which has been reported to be about 70% and above.2,15 Across these studies, when TTR was in the higher quartile, patients had an overall better level of health management. This has implications for the generalisability of these fi ndings to an Australian population and, consequently, to the cost-effectiveness in an Australian setting.2
Challenges for chronic AF anticoagulation management in the community Whatever the choice of anticoagulant, it is imperative that patient-related factors are considered in the selection and management of chronic AF therapies that are primarily self-administered in the community. This is particularly relevant when considering translation from clinical trial settings into the wider clinical practice environment. It is known that clinical use will be different from that within the controlled clinical trial
Perspectives Summary of key studies comparing dabigatran, rivaroxaban or apixaban with warfarin2
Study design RE-LY9
ROCKET AF11
ARISTOTLE12
Baseline characteristics Comorbidities
Prospective, multicentre, Mean age, 71.5 years; male, 64% multinational, randomised, parallel-group trial: dabigatran (110 mg or 150 mg twice daily) v adjusted warfarin dose (N = 18 133)
Double-blinded randomised controlled trial: rivaroxaban (20 mg daily) v adjusted warfarin dose (N = 14 264) Double-blinded randomised controlled trial: apixaban (5 mg twice daily) v adjusted warfarin dose (N = 18 201)
Reduction of total stroke or systemic embolism, HR or RR (95% CI)
History of TIA/stroke, 20%; previous MI, 17%; hypertension, 79%; diabetes, 23%
Reduction of bleeds, OR (95% CI)
110 mg: RR, 0.91 (0.74–1.11)
110 mg: major bleed, 0.80 (0.69–0.93); major GI bleed, 1.10 (0.86–1.41); ICH, 0.31 (0.20–0.47); all-cause mortality, 0.91 (0.80–1.03)
150 mg: RR, 0.66 (0.53–0.82)
150 mg: major bleed, 0.93 (0.81–1.07); major GI bleed, 1.50 (1.19–1.89); ICH, 0.40 (0.27–0.60); all-cause mortality, 0.88 (0.77–1.00) Major bleed, 1.04 (0.90–1.20); major GI bleed, 1.60 (1.29–1.98); ICH, 0.67 (0.47–0.93); all-cause mortality, 0.85 (0.70–1.02)
Mean age, 73.0 years; male, 60%
History of TIA/stroke, 55%; previous MI, 17%; hypertension, 90%; diabetes, 40%
HR on PP, 0.79 (0.66–0.96); HR on ITT, 0.88 (0.74–1.03)
Mean age, 70.0 years; male, 65%
History of TIA/stroke, 19%; previous MI, 14%; hypertension, 87%; diabetes, 25%
HR, 0.79 (0.66–0.95)
Major bleed, 0.69 (0.60–0.80); major GI bleed, 0.89 (0.70–1.15); ICH, 0.42 (0.30–0.58); all-cause mortality, 0.89 (0.80–0.99)
GI = gastrointestinal. HR = hazard ratio. ICH = intracranial haemorrhage. ITT = intention-to-treat analysis. MI = myocardial infarction. OR = odds ratio. PP = per-protocol analysis. RR = relative risk. TIA = transient ischaemic attack.
setting. Recently published data on local experience in the use of dabigatran has shown this to be the case.16 Compared with the participants in the RE-LY trial,9 the Australian cohort had older participants, fewer patients with significant renal impairment, and a higher TTR of 70%. These differences will play a role in the real world, outside of the control of the clinical trial arena. The challenges faced by Australian health care providers are that many patients with AF are older, with multiple comorbidities and on a range of other chronic therapies, and are self-managing their anticoagulation in the community.17 Selection of the appropriate therapy requires not only consideration of specific aspects of the individual drug but, even more importantly, the services and supports for the ongoing management and care after treatment initiation. In the case of chronic disease management in older patients, approaches to improving anticoagulation must not only focus on medication initiation but also on the patients and the changes that inevitably occur in their ability to self-manage.17,18 A wide range of recommendations from the Department of Health and Ageing review aims to improve health outcomes and remove barriers to the use of warfarin by improving the quality of use.2 We believe that these recommendations should be progressed. A number of them specifically relate to strategies to improve chronic anticoagulation management, including (i) a requirement for national guidelines that are disseminated and implemented; (ii) guidelines for patient management; (iii) availability and coordination of community-based anticoagulation support services for patients for whom therapy is initiated in the community; (iv) optimisation of TTR; and (v) a nationally endorsed shared care model for warfarin monitoring and management.2 We support these recommendations and believe that increased emphasis should be given to improvements in strategies focusing specifically on patient-related factors that influence the management of oral anticoagulation when self-administered in the community. In addition to demographic and clinical risk factors, we identified
in older patients, approaches to improving anticoagulation must not only focus on medication initiation but also on the patients and the changes that inevitably occur in their ability to selfmanage
the following specific patient factors as independent risk factors for instability of anticoagulation and bleeding risk in response to warfarin: cognitive impairment, social isolation, depressed mood, inadequate health literacy, and functional dependence.8 There was a 3.4-fold increased risk of bleeding when multiple psychosocial factors were present.8 Strategies to improve chronic AF anticoagulation management in the community must take patient factors into account, not only at the drug selection and initiation of treatment stage but also through ongoing assessment as the patient’s age increases.19 Cognitive decline has been linked to ageing. Patients with progressive cognitive impairment, and who remain responsible for their own medication management, may have increasing difficulty routinely administering and monitoring any of their medications, not just warfarin. Including patient factors in national guidelines and shared care models is fundamental to improving anticoagulation in AF through regular patient assessment.
Conclusion Patient factors must be taken into account not only at the point of drug selection but as a routine component of care. These factors include poor cognition, depressed mood, functional dependence, social isolation and inadequate health literacy. Improved models of care are required to monitor and manage patient factors to ensure safe and efficacious anticoagulation, irrespective of the specific drug involved. Translation of clinical trial fi ndings into the broader clinical environment must also include consideration of all the factors that influence patient variability. Further, improved stroke prevention and AF management are required and include medication innovation as well as innovation in models of patient care. Irrespective of whether warfarin or a NOAC is chosen, the challenges for improving management and monitoring in potentially complex patient cohorts remain. MJA 199 (3) · 5 August 2013
157
Perspectives Acknowledgements: This work was supported by a grant from the National Health and Medical Research Council (436763) and approved by the human research ethics committees of Monash University and Cabrini Health. We thank the patients and general practitioners for participating in the research.
10 ROCKET AF Study Investigators. Rivaroxaban -- once daily, oral, direct
Competing interests: No relevant disclosures.
11
Provenance: Not commissioned; externally peer reviewed. 1 2
3
4
5 6
7
8
9
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-988. Australian Government Department of Health and Ageing. Review of anticoagulation therapies in atrial fibrillation. Canberra: Commonwealth of Australia, 2012: 171. http://www.pbs.gov.au/info/publication/factsheets/ shared/anticoagulation-review (accessed Jun 2013). Nutescu EA, Shapiro NL, Chevalier A, Amin AN. A pharmacologic overview of current and emerging anticoagulants. Cleve Clin J Med 2005; 72 Suppl 1: S2-S6. Tran HA, Chunilal SD, Harper PL, et al; Australasian Society of Thrombosis and Haemostasis. An update of consensus guidelines for warfarin reversal. Med J Aust 2013; 198: 198-199. White RH, Beyth RJ, Zhou H, Romano PS. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999; 107: 414-424. van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briët E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993; 153: 1557-1562. Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689-2696. Diug B, Evans S, Lowthian J, et al. The unrecognized psychosocial factors contributing to bleeding risk in warfarin therapy. Stroke 2011; 42: 2866-2871. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation: rationale and design of the ROCKET AF study. Am Heart J 2010; 159: 340-347. Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
12 Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and
Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-982. 13 Banerjee A, Lane DA, Torp-Pedersen C, Lip GY. Net clinical benefit of
new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107: 584-589. 14 Schneeweiss S, Gagne JJ, Patrick AR, et al. Comparative efficacy and safety
of new oral anticoagulants in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2012; 5: 480-486. 15 Wallentin L, Yusuf S, Ezekowitz MD, et al; RE-LY Investigators. Efficacy
and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376: 975-983. 16 Lim SL, Maxwell E. An audit of dabigatran etexilate prescribing in Victoria
[letter]. Med J Aust 2013; 198: 314-315. 17 Lowthian JA, Diug BO, Evans SM, et al. Who is responsible for the care of
patients treated with warfarin therapy? Med J Aust 2009; 190: 674-677. 18 Lip GY, Frison L, Halperin JL, Lane DA. Identifying patients at high risk for
stroke despite anticoagulation: a comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort. Stroke 2010; 41: 2731-2738. 19 Lackie CL, Garbarino KA, Pruetz JA. Warfarin therapy for atrial fibrillation in
the elderly. Ann Pharmacother 2002; 36: 200-204.
Call for papers to coincide with conference presentations The MJA is looking for high-quality clinically orientated research or other manuscripts for simultaneous publication with presentation at major conferences. Manuscripts should be submitted at least 3 months before the date of the conference to allow time for peer review. The covering letter must request conference fasttracking, and include the name, date and location of the conference. Manuscripts must comply with the MJA’s Instructions for authors. Priority will be given to manuscripts with relevance to a wide variety of medical practitioners.
Broadcast your work to the world – all MJA research articles are now open access!
158
MJA 199 (3) · 5 August 2013
For full details visit us at
www.mja.com.au/journal/mja-instructions-authors
❑
Replacing warfarin for better or worse: patient factors and future directions Care models must consider patient factors to ensure safe and effective use of patient-administered anticoagulants
I
n Australia, atrial fibrillation (AF) affects 1%–2% of the population, placing them at a fivefold increased risk of stroke.1 The prevalence of AF increases sharply with age, with 50% of patients aged 75 years or over.2 Warfarin has been used clinically for more than 70 years and is the mainstay anticoagulant for prophylaxis of stroke as well as for the management of AF. However, in recent years, the novel oral anticoagulants (NOACs) dabigatran, rivaroxaban and apixaban have been developed. These promise more efficacy than warfarin in stroke prevention, while being safer and easier to use.3 A recent review by the Australian Government Department of Health and Ageing provided perspectives on current and future options for improving the use of anticoagulation therapies in managing patients with AF.2 In this article, we focus on strategies to improve anticoagulation management in patients with AF in light of the increasing utility of NOACs.
Warfarin in clinical practice Despite the availability of oral alternative therapies, warfarin — a vitamin K antagonist — remains efficacious and cost-effective in reducing the incidence of stroke in patients with AF.4 However, warfarin has a narrow therapeutic window, resulting in an unpredictable anticoagulant effect that necessitates frequent monitoring and dosage adjustment.4 Further, warfarin is associated with the clinical trade-off between the risk of ischaemic stroke and an increased risk of bleeding, particularly intracranial haemorrhage. As a consequence, a range of risk factors that can influence warfarin stability have been identified and are well known in clinical practice.5,6 These complexities have resulted in underuse of warfarin, particularly among older people, where the risk of cerebrovascular and cardiovascular events is highest.7 Although warfarin has been used clinically for many decades, there is an ongoing need to improve the monitoring and management of patients who receive it. Optimisation of time in the therapeutic range (TTR) is the key to improving patient outcomes. This requires identification of factors that can influence TTR and the incorporation of management strategies.2 Although multiple comorbidities and concomitant medications are regularly cited as reasons for poor TTR, other relevant patient factors, such as cognitive impairment and inadequate health literacy, should be considered, as these have been shown to influence anticoagulation control.8 156
MJA 199 (3) · 5 August 2013
Basia O Diug BBioMedSci(Hons), Lecturer and Research Fellow1
Judy A Lowthian PhD, MPH, BAppSc(SpPath), Senior Research Fellow1
Michael Dooley BPharm, GradDipHospPharm, Director of Pharmacy and Professor of Clinical Pharmacy2
1 School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC. 2 Alfred Hospital, Melbourne, VIC.
basia.diug@ monash.edu
doi: 10.5694/mja12.11863
Clinical trials of the new anticoagulants Dabigatran, a thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, are the fi rst oral alternatives to warfarin to be made available for the prevention of stroke and systemic embolism in patients with non-valvular AF. All three NOACs have demonstrated effectiveness in multinational randomised clinical trials although, to date, no studies have directly compared them. Pivotal trials for dabigatran (RELY),9 rivaroxaban (ROCKET AF)10,11 and apixaban (ARISTOTLE)12 recruited patients from 40 different countries, with the aim of evaluating their respective efficacy for the prevention of stroke and the risk of haemorrhage compared with warfarin (Box). The results look promising, with all three NOACs demonstrating non-inferiority to warfarin for stroke and systemic embolism prevention.9-12 However, their most consistent clinical benefit is that they are superior to warfarin when it comes to the rate of intracerebral haemorrhage and haemorrhagic stroke.10,12 Further, they have the notable practical advantages of involving fi xed dosages and not requiring international normalised ratio monitoring.3 Although these results show clear benefits, there are some significant differences between the trials, including different defi nitions at end points such as major bleeding, differences in follow-up periods, and different distribution of patients in various countries, making direct comparison difficult.13,14 Most notably, consideration must be given to the quality of warfarin management and stability in the control arms, as this varies markedly and is also at variance with that seen in clinical practice. The mean TTRs for patients taking warfarin in the three NOAC trials9-11 were 64%, 55% and 62%, respectively. These proportions are significantly lower than that found in the Australian population, which has been reported to be about 70% and above.2,15 Across these studies, when TTR was in the higher quartile, patients had an overall better level of health management. This has implications for the generalisability of these fi ndings to an Australian population and, consequently, to the cost-effectiveness in an Australian setting.2
Challenges for chronic AF anticoagulation management in the community Whatever the choice of anticoagulant, it is imperative that patient-related factors are considered in the selection and management of chronic AF therapies that are primarily self-administered in the community. This is particularly relevant when considering translation from clinical trial settings into the wider clinical practice environment. It is known that clinical use will be different from that within the controlled clinical trial
Perspectives Summary of key studies comparing dabigatran, rivaroxaban or apixaban with warfarin2
Study design RE-LY9
ROCKET AF11
ARISTOTLE12
Baseline characteristics Comorbidities
Prospective, multicentre, Mean age, 71.5 years; male, 64% multinational, randomised, parallel-group trial: dabigatran (110 mg or 150 mg twice daily) v adjusted warfarin dose (N = 18 133)
Double-blinded randomised controlled trial: rivaroxaban (20 mg daily) v adjusted warfarin dose (N = 14 264) Double-blinded randomised controlled trial: apixaban (5 mg twice daily) v adjusted warfarin dose (N = 18 201)
Reduction of total stroke or systemic embolism, HR or RR (95% CI)
History of TIA/stroke, 20%; previous MI, 17%; hypertension, 79%; diabetes, 23%
Reduction of bleeds, OR (95% CI)
110 mg: RR, 0.91 (0.74–1.11)
110 mg: major bleed, 0.80 (0.69–0.93); major GI bleed, 1.10 (0.86–1.41); ICH, 0.31 (0.20–0.47); all-cause mortality, 0.91 (0.80–1.03)
150 mg: RR, 0.66 (0.53–0.82)
150 mg: major bleed, 0.93 (0.81–1.07); major GI bleed, 1.50 (1.19–1.89); ICH, 0.40 (0.27–0.60); all-cause mortality, 0.88 (0.77–1.00) Major bleed, 1.04 (0.90–1.20); major GI bleed, 1.60 (1.29–1.98); ICH, 0.67 (0.47–0.93); all-cause mortality, 0.85 (0.70–1.02)
Mean age, 73.0 years; male, 60%
History of TIA/stroke, 55%; previous MI, 17%; hypertension, 90%; diabetes, 40%
HR on PP, 0.79 (0.66–0.96); HR on ITT, 0.88 (0.74–1.03)
Mean age, 70.0 years; male, 65%
History of TIA/stroke, 19%; previous MI, 14%; hypertension, 87%; diabetes, 25%
HR, 0.79 (0.66–0.95)
Major bleed, 0.69 (0.60–0.80); major GI bleed, 0.89 (0.70–1.15); ICH, 0.42 (0.30–0.58); all-cause mortality, 0.89 (0.80–0.99)
GI = gastrointestinal. HR = hazard ratio. ICH = intracranial haemorrhage. ITT = intention-to-treat analysis. MI = myocardial infarction. OR = odds ratio. PP = per-protocol analysis. RR = relative risk. TIA = transient ischaemic attack.
setting. Recently published data on local experience in the use of dabigatran has shown this to be the case.16 Compared with the participants in the RE-LY trial,9 the Australian cohort had older participants, fewer patients with significant renal impairment, and a higher TTR of 70%. These differences will play a role in the real world, outside of the control of the clinical trial arena. The challenges faced by Australian health care providers are that many patients with AF are older, with multiple comorbidities and on a range of other chronic therapies, and are self-managing their anticoagulation in the community.17 Selection of the appropriate therapy requires not only consideration of specific aspects of the individual drug but, even more importantly, the services and supports for the ongoing management and care after treatment initiation. In the case of chronic disease management in older patients, approaches to improving anticoagulation must not only focus on medication initiation but also on the patients and the changes that inevitably occur in their ability to self-manage.17,18 A wide range of recommendations from the Department of Health and Ageing review aims to improve health outcomes and remove barriers to the use of warfarin by improving the quality of use.2 We believe that these recommendations should be progressed. A number of them specifically relate to strategies to improve chronic anticoagulation management, including (i) a requirement for national guidelines that are disseminated and implemented; (ii) guidelines for patient management; (iii) availability and coordination of community-based anticoagulation support services for patients for whom therapy is initiated in the community; (iv) optimisation of TTR; and (v) a nationally endorsed shared care model for warfarin monitoring and management.2 We support these recommendations and believe that increased emphasis should be given to improvements in strategies focusing specifically on patient-related factors that influence the management of oral anticoagulation when self-administered in the community. In addition to demographic and clinical risk factors, we identified
in older patients, approaches to improving anticoagulation must not only focus on medication initiation but also on the patients and the changes that inevitably occur in their ability to selfmanage
the following specific patient factors as independent risk factors for instability of anticoagulation and bleeding risk in response to warfarin: cognitive impairment, social isolation, depressed mood, inadequate health literacy, and functional dependence.8 There was a 3.4-fold increased risk of bleeding when multiple psychosocial factors were present.8 Strategies to improve chronic AF anticoagulation management in the community must take patient factors into account, not only at the drug selection and initiation of treatment stage but also through ongoing assessment as the patient’s age increases.19 Cognitive decline has been linked to ageing. Patients with progressive cognitive impairment, and who remain responsible for their own medication management, may have increasing difficulty routinely administering and monitoring any of their medications, not just warfarin. Including patient factors in national guidelines and shared care models is fundamental to improving anticoagulation in AF through regular patient assessment.
Conclusion Patient factors must be taken into account not only at the point of drug selection but as a routine component of care. These factors include poor cognition, depressed mood, functional dependence, social isolation and inadequate health literacy. Improved models of care are required to monitor and manage patient factors to ensure safe and efficacious anticoagulation, irrespective of the specific drug involved. Translation of clinical trial fi ndings into the broader clinical environment must also include consideration of all the factors that influence patient variability. Further, improved stroke prevention and AF management are required and include medication innovation as well as innovation in models of patient care. Irrespective of whether warfarin or a NOAC is chosen, the challenges for improving management and monitoring in potentially complex patient cohorts remain. MJA 199 (3) · 5 August 2013
157
Perspectives Acknowledgements: This work was supported by a grant from the National Health and Medical Research Council (436763) and approved by the human research ethics committees of Monash University and Cabrini Health. We thank the patients and general practitioners for participating in the research.
10 ROCKET AF Study Investigators. Rivaroxaban -- once daily, oral, direct
Competing interests: No relevant disclosures.
11
Provenance: Not commissioned; externally peer reviewed. 1 2
3
4
5 6
7
8
9
Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-988. Australian Government Department of Health and Ageing. Review of anticoagulation therapies in atrial fibrillation. Canberra: Commonwealth of Australia, 2012: 171. http://www.pbs.gov.au/info/publication/factsheets/ shared/anticoagulation-review (accessed Jun 2013). Nutescu EA, Shapiro NL, Chevalier A, Amin AN. A pharmacologic overview of current and emerging anticoagulants. Cleve Clin J Med 2005; 72 Suppl 1: S2-S6. Tran HA, Chunilal SD, Harper PL, et al; Australasian Society of Thrombosis and Haemostasis. An update of consensus guidelines for warfarin reversal. Med J Aust 2013; 198: 198-199. White RH, Beyth RJ, Zhou H, Romano PS. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999; 107: 414-424. van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briët E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993; 153: 1557-1562. Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689-2696. Diug B, Evans S, Lowthian J, et al. The unrecognized psychosocial factors contributing to bleeding risk in warfarin therapy. Stroke 2011; 42: 2866-2871. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation: rationale and design of the ROCKET AF study. Am Heart J 2010; 159: 340-347. Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
12 Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and
Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-982. 13 Banerjee A, Lane DA, Torp-Pedersen C, Lip GY. Net clinical benefit of
new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107: 584-589. 14 Schneeweiss S, Gagne JJ, Patrick AR, et al. Comparative efficacy and safety
of new oral anticoagulants in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2012; 5: 480-486. 15 Wallentin L, Yusuf S, Ezekowitz MD, et al; RE-LY Investigators. Efficacy
and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010; 376: 975-983. 16 Lim SL, Maxwell E. An audit of dabigatran etexilate prescribing in Victoria
[letter]. Med J Aust 2013; 198: 314-315. 17 Lowthian JA, Diug BO, Evans SM, et al. Who is responsible for the care of
patients treated with warfarin therapy? Med J Aust 2009; 190: 674-677. 18 Lip GY, Frison L, Halperin JL, Lane DA. Identifying patients at high risk for
stroke despite anticoagulation: a comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort. Stroke 2010; 41: 2731-2738. 19 Lackie CL, Garbarino KA, Pruetz JA. Warfarin therapy for atrial fibrillation in
the elderly. Ann Pharmacother 2002; 36: 200-204.
Call for papers to coincide with conference presentations The MJA is looking for high-quality clinically orientated research or other manuscripts for simultaneous publication with presentation at major conferences. Manuscripts should be submitted at least 3 months before the date of the conference to allow time for peer review. The covering letter must request conference fasttracking, and include the name, date and location of the conference. Manuscripts must comply with the MJA’s Instructions for authors. Priority will be given to manuscripts with relevance to a wide variety of medical practitioners.
Broadcast your work to the world – all MJA research articles are now open access!
158
MJA 199 (3) · 5 August 2013
For full details visit us at
www.mja.com.au/journal/mja-instructions-authors
❑
