A need to re-focus efforts to improve long-term prognosis after stroke in China
Authors: Simiao Wu, Craig S Anderson
Journal: The Lancet Global Health (2020)

The Global Burden of Disease Study 2016 estimated that one in four people across the world will have a stroke in their lifetime.1Feigin VL Nguyen G Cercy K et al.Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016.N Engl J Med. 2018; 379: 2429-2437Crossref PubMed Scopus (632) Google Scholar For China, which constitutes a fifth of the world's population, this figure is two in five, which, along with the high incidence, mortality, and disability-adjusted life years (DALYs) associated with stroke, is another metric that reflects the heavy burden of stroke in this country.2Johnson CO Nguyen M Roth GA et al.Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol. 2019; 18: 439-458Summary Full Text Full Text PDF PubMed Scopus (1401) Google Scholar Yet, despite successful efforts to improve acute stroke care in China in the past two decades,3Wu S Wu B Liu M et al.Stroke in China: advances and challenges in epidemiology, prevention, and management.Lancet Neurol. 2019; 18: 394-405Summary Full Text Full Text PDF PubMed Scopus (608) Google Scholar and more recently in raising awareness of early symptoms and the need for rapid access to stroke centres,4Zhao J Liu R Stroke 1-2-0: a rapid response programme for stroke in China.Lancet Neurol. 2017; 16: 27-28Summary Full Text Full Text PDF PubMed Scopus (45) Google Scholar much less attention has been given to post-discharge care. An improved understanding of the long-term prognosis for stroke would be a useful foundation upon which the uptake of current secondary prevention strategies, and the effectiveness of new strategies, can be assessed in China. Thus, the Article by Yiping Chen and colleagues in this issue of The Lancet Global Health5Chen Y Wright N Guo Y et al.Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0·5 million Chinese adults.Lancet Glob Health. 2020; 8: e580-e590Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar not only fills a gap in the knowledge base, but also highlights potential gaps in clinical practice, through their investigation of long-term prognosis after stroke in China. From the ongoing China Kadoorie Biobank study, they analysed a cohort of 489 586 community-dwelling residents from ten regions of China, aged 35–74 years and without a history of stroke or transient ischaemic attack at baseline, who were prospectively followed up for nearly a decade.5Chen Y Wright N Guo Y et al.Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0·5 million Chinese adults.Lancet Glob Health. 2020; 8: e580-e590Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar They found that around 9% of participants experienced a first stroke during the 9-year follow-up, one in ten of whom died within 28 days after the onset of stroke symptoms. Additionally, among those who survived for at least 28 days, the cumulative event rate of recurrent stroke was 41% (95% CI 41–42), and the cumulative rate of mortality was 17% (17–18) over the next 5 years. Considerable reassurance over the internal and external validity of these data is provided by the prospective cohort design: the authors systematically screened routine data collection systems for events using standard definitions, in a large population with wide-ranging sociodemographic characteristics, and regional diversity in health-care access and quality.6Lozano R Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016.Lancet. 2018; 391: 2236-2271Summary Full Text Full Text PDF PubMed Scopus (474) Google Scholar However, as the China Kadoorie Biobank study was primarily designed to assess associations between a wide range of risk factors and different diseases, no data are available on the extent to which vascular risk factors were controlled in relation to the use of proven treatments. Nevertheless, this study provides important contemporary stroke outcome data and serves as a benchmark for future studies of acute management and secondary prevention in China. Although the much higher 28-day case fatality for acute intracerebral haemorrhage (47% [46–48]) than for acute ischaemic stroke (3% [3–4]) is not too surprising, an important new finding was the similar rates (>40%) of recurrent stroke and major vascular events for these two major pathological stroke subtypes among 28-day survivors in the subsequent 5 years.5Chen Y Wright N Guo Y et al.Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0·5 million Chinese adults.Lancet Glob Health. 2020; 8: e580-e590Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar Presumably, inadequate secondary prevention contributed to the high long-term risk of serious vascular events. For patients in China, adherence to secondary medications is generally poor after discharge from hospital, with less than 50% maintaining secondary preventative treatment at 1 year.3Wu S Wu B Liu M et al.Stroke in China: advances and challenges in epidemiology, prevention, and management.Lancet Neurol. 2019; 18: 394-405Summary Full Text Full Text PDF PubMed Scopus (608) Google Scholar Patients and doctors should be alerted to the importance of long-term secondary prevention, irrespective of the type of stroke, and recognise that more accessible and easily monitored, cost-effective prevention strategies are urgently needed, especially in settings in which primary health-care services are underdeveloped. A polypill therapy, with a fixed-dose combination of aspirin, atorvastatin, hydrochlorothiazide, and either enalopril or valsartan, has been shown to be an effective, low-cost approach to reducing the risk of cardiovascular events, including stroke, in both primary and secondary prevention in Iran.7Roshandel G Khoshnia M Poustchi H et al.Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial.Lancet. 2019; 394: 672-683Summary Full Text Full Text PDF PubMed Scopus (134) Google Scholar Such an approach could be a model to be tested in China and other low-resource settings. Although addressing the risk of recurrent intracerebral haemorrhage is a priority for patients and caregivers after surviving a first intracerebral haemorrhage event, a key finding of Chen and colleagues was the high proportion (41%) of recurrent acute ischaemic stroke after a first event of intracerebral haemorrhage.5Chen Y Wright N Guo Y et al.Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0·5 million Chinese adults.Lancet Glob Health. 2020; 8: e580-e590Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar Given a common underlying mechanism—that of cerebral small vessel disease—prevention efforts should ideally target both haemorrhagic and ischaemic stroke after intracerebral haemorrhage. Effective blood pressure control is clearly the mainstay of secondary prevention in the setting of intracerebral haemorrhage, but evidence in recent years has raised the potential for antiplatelet therapy to offer benefits despite being counterintuitive because of the bleeding risk. The restart or stop antithrombotics randomised trial (RESTART), completed in 2018, showed that restarting antiplatelet therapy in 268 patients with intracerebral haemorrhage, versus avoiding therapy in 268 patients, proportionally reduced the risk of recurrent intracerebral haemorrhage (in 12 [4%] vs 23 [9%] patients; adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060) without affecting major occlusive vascular events (in 39 [15%] vs 38 [14%] patients; 1·02 [0·65–1·60]) over a median of 2·0 years (IQR 1·0–3·0).8Al-Shahi Salman R Dennis MS Sandercock PAG et al.Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial.Lancet. 2019; 393: 2613-2623Summary Full Text Full Text PDF PubMed Scopus (96) Google Scholar A meta-analysis of three observational cohorts involving 2801 patients with intracerebral haemorrhage further suggests that antiplatelet therapy after intracerebral haemorrhage, whether resumed or started de novo, is safe and does not increase adverse outcomes.9Murthy SB Biffi A Falcone GJ et al.Antiplatelet therapy after spontaneous intracerebral hemorrhage and functional outcomes.Stroke. 2019; 50: 3057-3063Crossref PubMed Scopus (16) Google Scholar As randomised evidence from larger and more diverse populations is required to influence clinical practice, the antiplatelet secondary prevention international randomised trial after intracerebral haemorrhage (ASPIRING; Rustam Al-Shahi Salman, University of Edinburgh, personal communication) is planned to investigate whether antiplatelet therapy after intracerebral haemorrhage is beneficial for the long-term prevention of all serious vascular events. Despite encouraging reductions in incidence and improved survival for stroke in many parts of the world, the absolute numbers of prevalent cases and DALYs from stroke continue to increase in ageing populations.2Johnson CO Nguyen M Roth GA et al.Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol. 2019; 18: 439-458Summary Full Text Full Text PDF PubMed Scopus (1401) Google Scholar The emerging evidence of poor long-term prognosis warrants expanded efforts in the prolonged campaign against stroke. A key component of these efforts will involve widely accessible and cost-effective strategies for secondary prevention that cover post-discharge care, in line with similar strategies for primary prevention and acute management. SW reports a grant from the National Natural Science Foundation of China (81701156). CSA has received grants from the National Health and Medical Research Council of Australia (APP1175861 and APP1149987). He has also received grants for stroke research (IISR-2017-101947 and IISR-2018-102649), and lecture fees and travel reimbursement, from Takeda China. Mortality and recurrent vascular events after first incident stroke: a 9-year community-based study of 0·5 million Chinese adultsAfter a first stroke, the risk of recurrence or death within 5 years was high among this population of Chinese adults. Urgent improvements to secondary prevention of stroke in China are needed to reduce these risks. Full-Text PDF Open Access