- Email: [email protected]
Tackling the global diabetes burden: will screening help?
Comment
the rights of psychiatric patients,1,9 as a result of the scarcity of national and local mental health laws, with the exception of a few major cities.9,10 In 1985, a committee started drafting the Mental Health Law of the People’s Republic of China; the draft was revised 15 times up to 2005.10 The revised draft of the National Mental Health Law was released by the Standing Committee of the National People’s Congress on Oct 29, 2011,11 and was formally approved on Oct 26, 2012 to come into effect from May 1, 2013.12 Another challenging issue is the lack of valid national data about the prevalence of psychiatric disorders. The country’s only two national psychiatric surveys were in 1982 and 1993.13,14 A new nationwide psychiatric survey is urgently needed, because having solid epidemiological data is a fundamental step if mental health services are to be shored up and strategies devised for the effective implementation of measures to reduce the multitude of harmful consequences of under-recognised and untreated psychiatric disorders. In recent years, the endeavours of central and local governments in China and mental health professionals have improved access to, and the quality of, the mental health system. However, much progress is still needed to address the major challenges facing China’s mental health services.
Beijing Anding Hospital, Capital Medical University, Beijing, China (Y-TX); Division of Services Research, Department of Psychiatry, School of Medicine, University of Maryland, MD 21201, USA (Y-TX); Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China (Y-TX, HFKC); Peking University Institute of Mental Health, Beijing, China (XY); Association for the Improvement of Mental Health Programs, Geneva, Switzerland (NS), and University of Notre Dame Australia, Marian Centre, Perth, WA, Australia (GSU) [email protected] We declare that we have no conflicts of interest. 1 2
3 4 5
6 7 8 9
10 11 12
13 14
*Yu-Tao Xiang, Xin Yu, Norman Sartorius, Gabor S Ungvari, Helen F K Chiu
The Lancet. Psychiatric institutions in China. Lancet 2010; 376: 2. Phillips MR, Zhang J, Shi Q, et al. Prevalence, treatment, and associated disability of mental disorders in four provinces in China during 2001–05: an epidemiological survey. Lancet 2009; 373: 2041–53. Cyranoski D. China tackles surge in mental illness. Nature 2010; 468: 145. Ng CH, Ma H, Yu X, et al. China-Australia-Hong Kong tripartite community mental health training program. Asia Pac Psychiatry 2009; 1: 90–97. Wu XM, Ma N. Report of central subsidies to local management of patients with severe mental illnesses. Beijing, China: Peking University Institute of Mental Health, 2012 (in Chinese). Phillips MR, Li X, Zhang Y. Suicide rates in China, 1995–99. Lancet 2002; 359: 835–40. Hawton K, van Heeringen K. Suicide. Lancet 2009; 373: 1372–81. Zhang J, Jing J. Sociological analysis of the downward trend of suicide rates in China. Soc Sci China 2011; 5: 97–113 (in Chinese). Qian HP. The chaos behind the label of mental illness. Beijing News May 31, 2011 (in Chinese). http://epaper.bjnews.com.cn/images/2011-05/31/A22/ A22531C.pdf (accessed June 6, 2011). Xiang YT, Yu X, Chiu HF. Compulsory admission to psychiatric hospitals in China. Lancet 2010; 376: 1145–46. Xiang YT, Yu X, Ungvari GS, Lee EH, Chiu HF. China’s National Mental Health Law: a 26-year work in progress. Lancet 2012; 379: 780–82. Zhou S. Law may shield rights of mentally ill. People’s Daily Online Oct 31, 2012. http://english.peopledaily.com.cn/90882/7999098.html (accessed Nov 1, 2012). Cooper JE, Sartorius N. Mental disorders in China: results of the National Epidemiological Survey in 12 areas. London: Gaskell, 1996. Wang JR, Wang DP, Shen YC, et al. Epidemiological survey on affective disorder in 7 areas of China. Chin J Psychiatry 1998; 5: 75–77 (in Chinese).
Tackling the global diabetes burden: will screening help? Published Online October 4, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)61682-1 See Comment page 1723 See Articles page 1741
1716
Worldwide, cases of type 2 diabetes have doubled from nearly 150 million in 1980 to almost 350 million today,1 and effective strategies to reduce the burden of disease are greatly needed. A large and highly variable proportion of cases are undiagnosed,2 and in view of the available evidence-based treatments,3 early detection through diabetes screening is worth careful consideration. Diabetes screening and diagnosis can be done with relative ease, which further escalates popular support for wide-scale screening. However, these compelling arguments overlook the screening costs, potential harms, and lack of clear evidence that screening improves health outcomes compared with
current routine clinical diagnosis. In The Lancet, Rebecca Simmons and colleagues4 report their findings from the ADDITION study, the most earnest attempt to date to try to settle the diabetes screening quandary. The ADDITION study is a clinic-level cluster randomised trial of patients aged 40–69 years who are receiving care from general practices in eastern England, and represent the top 25% of the risk distribution for undiagnosed diabetes.4 Entire clinics were randomly assigned to screening or no screening (control group). In the screening clinics, treatment focused on glycaemic control and cardiovascular risk reduction through two care patterns: intensive multifactorial diabetes treatment or www.thelancet.com Vol 380 November 17, 2012
standard national guideline-based diabetes care. This study has both a pragmatic public health design with intention-to-screen while integrating a clinical design of intensive versus standard treatment. Clinic-level randomisation also allowed better uniformity across the interventions. Of 16 047 individuals invited for screening, 466 (3%) were newly diagnosed with diabetes. After a 10-year follow-up, there was no significant difference in all-cause mortality between screening and control groups (hazard ratio 1·06, 95% CI 0·90–1·25). Moreover, the mortality hazard ratios for cardiovascular disease, cancer, and diabetes were similar in the intervention and control populations, leaving no evidence of longterm mortality benefits associated with screening—a finding not unlike the small non-significant reduction in cardiovascular events and death found in a similar study with a shorter follow-up period.5 Long-term microvascular benefits, such as diabetic retinopathy and kidney disease, are not reported. This study has also previously reported on screening risks for participants such as anxiety and depression, which were found to be low;6 however, it found little beneficial change in lifestyle behaviours, with the exception of modest improvement in some dietary habits.7 Until the ADDITION study, diabetes screening policies had been led by indirect evidence—such as the benefits of preventive care early in the course of diagnosis— or used computer models to simulate progression of diabetes from onset for those screen-detected and those with routine clinical diagnosis to development of long-term outcomes and ultimately to death.8,9 These computer models track long-term outcomes only for the cohort with diabetes (screen-detected and routine clinically detected); those who never develop diabetes are not followed up, with their contribution limited to screening costs (true negatives) in economic studies. By contrast, Simmons and colleagues4 followed up the entire population, including those with and without diabetes, and report overall population-based mortality. This approach limits our understanding of morbidity and mortality in the diabetes cohort (ie, those screendetected and those detected through routine clinical diagnosis in the control group). The absence of a robust evidence base has led to a fairly narrow spectrum of screening recommendations, with almost none calling for population-wide screening but most recommending some form of risk stratification www.thelancet.com Vol 380 November 17, 2012
UIG via Getty Images
Comment
and opportunistic detection in clinical settings. These recommendations range from testing adults with hypertension,10 to a broader set of diabetes risk factors (age, obesity, and family history),11 linking screening to the country’s health situation and capacity to support it,12 and to clinical decision algorithms.13 Despite ADDITION’s importance as the first major trial of diabetes screening, we should use care in its interpretation for different populations. The study population’s prevalence of newly diagnosed diabetes was low (3%), and countries with higher prevalence of undiagnosed diabetes and low care quality could conceivably see a wider range and magnitude of benefits, assuming adequate resources are available to care for the added burden of newly detected cases. Perhaps the most pivotal factor for the future nuances of screening policy is how primary prevention programmes take shape around the world. Structured lifestyle interventions and metformin treatment in high-risk adults are highly cost-effective, and modelling studies suggest that screening for diabetes and high-risk states in combination is more effective than screening for diabetes alone.14 This strategy assumes that effective prevention programmes are available to high-risk cases. Ongoing follow-up studies examining the long-term benefits (ie, morbidity and mortality) within primary prevention study cohorts will be an important part of this equation.15 Ultimately, the judgment on screening will depend on more than just mortality as an outcome. Screening and early actions could have an important benefit 1717
Comment
in terms of chronic disease risk factor improvement, incidence of disease, morbidity, quality of life, and costs, without materially affecting mortality. If we are to rely on cost-effectiveness modelling as a means to guide screening policy, we will have to place a lot of faith in the assumptions and effect of early identification on quality of life. Simmons and colleagues increase the doubt about the value of wide-scale screening for undiagnosed diabetes alone, and deserve credit for tackling the screening quandary head-on. Nevertheless, for any one study to address the diverse factors that affect screening policies—ranging from the magnitude of population burden of disease to the capacity and effectiveness of prevention approaches—is a tall order. Screening recommendations are therefore likely to be countryspecific and context-specific for the foreseeable future.
2 3 4
5
6
7
8 9
10
11
*Michael M Engelgau, Edward W Gregg National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA [email protected] We declare that we have no conflicts of interest. The views expressed in this Comment are those of the authors, and do not necessarily represent those of the Centers for Disease Control and Prevention. 1
Danaei G, Finucane MM, Lu Y, et al, on behalf of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood Glucose). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 2011; 378: 31–40.
12 13
14
15
Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362: 1090–101. Simmons RK, Echouffo-Tcheugui JB, Griffin SJ. Screening for type 2 diabetes: an update of the evidence. Diabetes Obes Metab 2010; 12: 838–44. Simmons RK, Echouffo-Tcheugui JB, Sharp SJ, et al. Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial. Lancet 2012; published online Oct 4. http://dx.doi.org/10.1016/S0140-6736(12)61422-6. Griffin SJ, Borch-Johnsen K, Davies MJ, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet 2011; 378: 156–67. Eborall HC, Griffin SJ, Prevost AT, Kinmonth AL, French DP, Sutton S. Psychological impact of screening for type 2 diabetes: controlled trial and comparative study embedded in the ADDITION (Cambridge) randomised controlled trial. BMJ 2007; 335: 486. Mai KS, Sandbaek A, Borch-Johnsen K, Lauritzen T. Are lifestyle changes achieved after participation in a screening programme for type 2 diabetes? The ADDITION Study, Denmark. Diabet Med 2007; 24: 1121–28. Engelgau MM. Trying to predict the future for people with diabetes: a tough but important task. Ann Intern Med 2005; 143: 301–02. Kahn R, Alperin P, Eddy D, et al. Age at initiation and frequency of screening to detect type 2 diabetes: a cost-effectiveness analysis. Lancet 2010; 375: 1365–74. Norris SL, Kansagara D, Bougatsos C, Fu R. Screening adults for type 2 diabetes: a review of the evidence for the US Preventive Services Task Force. Ann Intern Med 2008; 148: 855–68. American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011; 34 (suppl 1): S11–61. WHO. Screening for type 2 diabetes. Geneva: World Health Organization, 2003. Chatterton H, Younger T, Fischer A, Khunti K. Risk identification and interventions to prevent type 2 diabetes in adults at high risk: summary of NICE guidance. BMJ 2012; 345: e4624. Gillies CL, Lambert PC, Abrams KR, et al. Different strategies for screening and prevention of type 2 diabetes in adults: cost effectiveness analysis. BMJ 2008; 336: 1180–85. Uusitupa M, Peltonen M, Lindstrom J, et al. Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study— secondary analysis of the randomized trial. PLoS One 2009; 4: e5656.
Science Photo Library
Apixaban in atrial fibrillation: does predicted risk matter?
Published Online October 2, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)61673-0 See Articles page 1749
1718
Since its discovery in 1922,1 warfarin has been the major therapeutic agent for reduction of thromboembolic risk in patients with atrial fibrillation. Its benefits are well documented, and include a 64% relative risk reduction in stroke.2 However, drug and diet interactions can lead to an unpredictable dose response and can reduce its clinical effectiveness, sometimes with catastrophic results. Furthermore, the need for regular monitoring makes it unattractive for many patients. As a result, use of warfarin in patients with atrial fibrillation is not ideal, especially in those at highest risk for thromboembolic events.3 What is key, however, is that warfarin is safe when the patient’s international normalised ratio (INR) stays within the therapeutic range, and complications
usually occur when it does not—ie, bleeding can occur when the INR is high and ischaemic stroke might occur when INR is low. Therefore, novel oral anticoagulants that provide stable, predictable anticoagulation without the need for monitoring have long been of interest. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial4 compared warfarin with apixaban in 18 201 individuals with atrial fibrillation and one additional risk factor for thromboembolism. Results of this trial showed a benefit in favour of apixaban, both in terms of reduced stroke and systemic embolism (hazard ratio [HR] 0·79, 95% CI 0·66–0·95) and of reduced bleeding (HR for major bleeding 0·69, 0·60–0·80; HR www.thelancet.com Vol 380 November 17, 2012
the rights of psychiatric patients,1,9 as a result of the scarcity of national and local mental health laws, with the exception of a few major cities.9,10 In 1985, a committee started drafting the Mental Health Law of the People’s Republic of China; the draft was revised 15 times up to 2005.10 The revised draft of the National Mental Health Law was released by the Standing Committee of the National People’s Congress on Oct 29, 2011,11 and was formally approved on Oct 26, 2012 to come into effect from May 1, 2013.12 Another challenging issue is the lack of valid national data about the prevalence of psychiatric disorders. The country’s only two national psychiatric surveys were in 1982 and 1993.13,14 A new nationwide psychiatric survey is urgently needed, because having solid epidemiological data is a fundamental step if mental health services are to be shored up and strategies devised for the effective implementation of measures to reduce the multitude of harmful consequences of under-recognised and untreated psychiatric disorders. In recent years, the endeavours of central and local governments in China and mental health professionals have improved access to, and the quality of, the mental health system. However, much progress is still needed to address the major challenges facing China’s mental health services.
Beijing Anding Hospital, Capital Medical University, Beijing, China (Y-TX); Division of Services Research, Department of Psychiatry, School of Medicine, University of Maryland, MD 21201, USA (Y-TX); Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China (Y-TX, HFKC); Peking University Institute of Mental Health, Beijing, China (XY); Association for the Improvement of Mental Health Programs, Geneva, Switzerland (NS), and University of Notre Dame Australia, Marian Centre, Perth, WA, Australia (GSU) [email protected] We declare that we have no conflicts of interest. 1 2
3 4 5
6 7 8 9
10 11 12
13 14
*Yu-Tao Xiang, Xin Yu, Norman Sartorius, Gabor S Ungvari, Helen F K Chiu
The Lancet. Psychiatric institutions in China. Lancet 2010; 376: 2. Phillips MR, Zhang J, Shi Q, et al. Prevalence, treatment, and associated disability of mental disorders in four provinces in China during 2001–05: an epidemiological survey. Lancet 2009; 373: 2041–53. Cyranoski D. China tackles surge in mental illness. Nature 2010; 468: 145. Ng CH, Ma H, Yu X, et al. China-Australia-Hong Kong tripartite community mental health training program. Asia Pac Psychiatry 2009; 1: 90–97. Wu XM, Ma N. Report of central subsidies to local management of patients with severe mental illnesses. Beijing, China: Peking University Institute of Mental Health, 2012 (in Chinese). Phillips MR, Li X, Zhang Y. Suicide rates in China, 1995–99. Lancet 2002; 359: 835–40. Hawton K, van Heeringen K. Suicide. Lancet 2009; 373: 1372–81. Zhang J, Jing J. Sociological analysis of the downward trend of suicide rates in China. Soc Sci China 2011; 5: 97–113 (in Chinese). Qian HP. The chaos behind the label of mental illness. Beijing News May 31, 2011 (in Chinese). http://epaper.bjnews.com.cn/images/2011-05/31/A22/ A22531C.pdf (accessed June 6, 2011). Xiang YT, Yu X, Chiu HF. Compulsory admission to psychiatric hospitals in China. Lancet 2010; 376: 1145–46. Xiang YT, Yu X, Ungvari GS, Lee EH, Chiu HF. China’s National Mental Health Law: a 26-year work in progress. Lancet 2012; 379: 780–82. Zhou S. Law may shield rights of mentally ill. People’s Daily Online Oct 31, 2012. http://english.peopledaily.com.cn/90882/7999098.html (accessed Nov 1, 2012). Cooper JE, Sartorius N. Mental disorders in China: results of the National Epidemiological Survey in 12 areas. London: Gaskell, 1996. Wang JR, Wang DP, Shen YC, et al. Epidemiological survey on affective disorder in 7 areas of China. Chin J Psychiatry 1998; 5: 75–77 (in Chinese).
Tackling the global diabetes burden: will screening help? Published Online October 4, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)61682-1 See Comment page 1723 See Articles page 1741
1716
Worldwide, cases of type 2 diabetes have doubled from nearly 150 million in 1980 to almost 350 million today,1 and effective strategies to reduce the burden of disease are greatly needed. A large and highly variable proportion of cases are undiagnosed,2 and in view of the available evidence-based treatments,3 early detection through diabetes screening is worth careful consideration. Diabetes screening and diagnosis can be done with relative ease, which further escalates popular support for wide-scale screening. However, these compelling arguments overlook the screening costs, potential harms, and lack of clear evidence that screening improves health outcomes compared with
current routine clinical diagnosis. In The Lancet, Rebecca Simmons and colleagues4 report their findings from the ADDITION study, the most earnest attempt to date to try to settle the diabetes screening quandary. The ADDITION study is a clinic-level cluster randomised trial of patients aged 40–69 years who are receiving care from general practices in eastern England, and represent the top 25% of the risk distribution for undiagnosed diabetes.4 Entire clinics were randomly assigned to screening or no screening (control group). In the screening clinics, treatment focused on glycaemic control and cardiovascular risk reduction through two care patterns: intensive multifactorial diabetes treatment or www.thelancet.com Vol 380 November 17, 2012
standard national guideline-based diabetes care. This study has both a pragmatic public health design with intention-to-screen while integrating a clinical design of intensive versus standard treatment. Clinic-level randomisation also allowed better uniformity across the interventions. Of 16 047 individuals invited for screening, 466 (3%) were newly diagnosed with diabetes. After a 10-year follow-up, there was no significant difference in all-cause mortality between screening and control groups (hazard ratio 1·06, 95% CI 0·90–1·25). Moreover, the mortality hazard ratios for cardiovascular disease, cancer, and diabetes were similar in the intervention and control populations, leaving no evidence of longterm mortality benefits associated with screening—a finding not unlike the small non-significant reduction in cardiovascular events and death found in a similar study with a shorter follow-up period.5 Long-term microvascular benefits, such as diabetic retinopathy and kidney disease, are not reported. This study has also previously reported on screening risks for participants such as anxiety and depression, which were found to be low;6 however, it found little beneficial change in lifestyle behaviours, with the exception of modest improvement in some dietary habits.7 Until the ADDITION study, diabetes screening policies had been led by indirect evidence—such as the benefits of preventive care early in the course of diagnosis— or used computer models to simulate progression of diabetes from onset for those screen-detected and those with routine clinical diagnosis to development of long-term outcomes and ultimately to death.8,9 These computer models track long-term outcomes only for the cohort with diabetes (screen-detected and routine clinically detected); those who never develop diabetes are not followed up, with their contribution limited to screening costs (true negatives) in economic studies. By contrast, Simmons and colleagues4 followed up the entire population, including those with and without diabetes, and report overall population-based mortality. This approach limits our understanding of morbidity and mortality in the diabetes cohort (ie, those screendetected and those detected through routine clinical diagnosis in the control group). The absence of a robust evidence base has led to a fairly narrow spectrum of screening recommendations, with almost none calling for population-wide screening but most recommending some form of risk stratification www.thelancet.com Vol 380 November 17, 2012
UIG via Getty Images
Comment
and opportunistic detection in clinical settings. These recommendations range from testing adults with hypertension,10 to a broader set of diabetes risk factors (age, obesity, and family history),11 linking screening to the country’s health situation and capacity to support it,12 and to clinical decision algorithms.13 Despite ADDITION’s importance as the first major trial of diabetes screening, we should use care in its interpretation for different populations. The study population’s prevalence of newly diagnosed diabetes was low (3%), and countries with higher prevalence of undiagnosed diabetes and low care quality could conceivably see a wider range and magnitude of benefits, assuming adequate resources are available to care for the added burden of newly detected cases. Perhaps the most pivotal factor for the future nuances of screening policy is how primary prevention programmes take shape around the world. Structured lifestyle interventions and metformin treatment in high-risk adults are highly cost-effective, and modelling studies suggest that screening for diabetes and high-risk states in combination is more effective than screening for diabetes alone.14 This strategy assumes that effective prevention programmes are available to high-risk cases. Ongoing follow-up studies examining the long-term benefits (ie, morbidity and mortality) within primary prevention study cohorts will be an important part of this equation.15 Ultimately, the judgment on screening will depend on more than just mortality as an outcome. Screening and early actions could have an important benefit 1717
Comment
in terms of chronic disease risk factor improvement, incidence of disease, morbidity, quality of life, and costs, without materially affecting mortality. If we are to rely on cost-effectiveness modelling as a means to guide screening policy, we will have to place a lot of faith in the assumptions and effect of early identification on quality of life. Simmons and colleagues increase the doubt about the value of wide-scale screening for undiagnosed diabetes alone, and deserve credit for tackling the screening quandary head-on. Nevertheless, for any one study to address the diverse factors that affect screening policies—ranging from the magnitude of population burden of disease to the capacity and effectiveness of prevention approaches—is a tall order. Screening recommendations are therefore likely to be countryspecific and context-specific for the foreseeable future.
2 3 4
5
6
7
8 9
10
11
*Michael M Engelgau, Edward W Gregg National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA [email protected] We declare that we have no conflicts of interest. The views expressed in this Comment are those of the authors, and do not necessarily represent those of the Centers for Disease Control and Prevention. 1
Danaei G, Finucane MM, Lu Y, et al, on behalf of the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood Glucose). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 2011; 378: 31–40.
12 13
14
15
Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362: 1090–101. Simmons RK, Echouffo-Tcheugui JB, Griffin SJ. Screening for type 2 diabetes: an update of the evidence. Diabetes Obes Metab 2010; 12: 838–44. Simmons RK, Echouffo-Tcheugui JB, Sharp SJ, et al. Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial. Lancet 2012; published online Oct 4. http://dx.doi.org/10.1016/S0140-6736(12)61422-6. Griffin SJ, Borch-Johnsen K, Davies MJ, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet 2011; 378: 156–67. Eborall HC, Griffin SJ, Prevost AT, Kinmonth AL, French DP, Sutton S. Psychological impact of screening for type 2 diabetes: controlled trial and comparative study embedded in the ADDITION (Cambridge) randomised controlled trial. BMJ 2007; 335: 486. Mai KS, Sandbaek A, Borch-Johnsen K, Lauritzen T. Are lifestyle changes achieved after participation in a screening programme for type 2 diabetes? The ADDITION Study, Denmark. Diabet Med 2007; 24: 1121–28. Engelgau MM. Trying to predict the future for people with diabetes: a tough but important task. Ann Intern Med 2005; 143: 301–02. Kahn R, Alperin P, Eddy D, et al. Age at initiation and frequency of screening to detect type 2 diabetes: a cost-effectiveness analysis. Lancet 2010; 375: 1365–74. Norris SL, Kansagara D, Bougatsos C, Fu R. Screening adults for type 2 diabetes: a review of the evidence for the US Preventive Services Task Force. Ann Intern Med 2008; 148: 855–68. American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011; 34 (suppl 1): S11–61. WHO. Screening for type 2 diabetes. Geneva: World Health Organization, 2003. Chatterton H, Younger T, Fischer A, Khunti K. Risk identification and interventions to prevent type 2 diabetes in adults at high risk: summary of NICE guidance. BMJ 2012; 345: e4624. Gillies CL, Lambert PC, Abrams KR, et al. Different strategies for screening and prevention of type 2 diabetes in adults: cost effectiveness analysis. BMJ 2008; 336: 1180–85. Uusitupa M, Peltonen M, Lindstrom J, et al. Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study— secondary analysis of the randomized trial. PLoS One 2009; 4: e5656.
Science Photo Library
Apixaban in atrial fibrillation: does predicted risk matter?
Published Online October 2, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)61673-0 See Articles page 1749
1718
Since its discovery in 1922,1 warfarin has been the major therapeutic agent for reduction of thromboembolic risk in patients with atrial fibrillation. Its benefits are well documented, and include a 64% relative risk reduction in stroke.2 However, drug and diet interactions can lead to an unpredictable dose response and can reduce its clinical effectiveness, sometimes with catastrophic results. Furthermore, the need for regular monitoring makes it unattractive for many patients. As a result, use of warfarin in patients with atrial fibrillation is not ideal, especially in those at highest risk for thromboembolic events.3 What is key, however, is that warfarin is safe when the patient’s international normalised ratio (INR) stays within the therapeutic range, and complications
usually occur when it does not—ie, bleeding can occur when the INR is high and ischaemic stroke might occur when INR is low. Therefore, novel oral anticoagulants that provide stable, predictable anticoagulation without the need for monitoring have long been of interest. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial4 compared warfarin with apixaban in 18 201 individuals with atrial fibrillation and one additional risk factor for thromboembolism. Results of this trial showed a benefit in favour of apixaban, both in terms of reduced stroke and systemic embolism (hazard ratio [HR] 0·79, 95% CI 0·66–0·95) and of reduced bleeding (HR for major bleeding 0·69, 0·60–0·80; HR www.thelancet.com Vol 380 November 17, 2012