Evidence-based stroke medicine, past present and future

1. Evidence-based stroke medicine, past present and future Peter Sandercock University of Edinburgh, UK WSC, Brasilia Presidential Lecture 13th October 2012

2. Outline • Past: build the evidence base • Find the reliable evidence (RCT’s) • Review it systematically • Present: identify treatments that are • Effective, use widely • Ineffective/no evidence – do NOT use • Future • Identify the important questions • Focus on interventions for stroke in low-and middle-income countries

3. Past: work done so far on building the evidence base

4. The Cochrane Collaboration • International network of more than 28,000 dedicated people from over 100 countries. • Aim to help healthcare providers, policy-makers, patients, their advocates and carers, make well-informed decisions about health care, • Preparing, updating, and promoting the accessibility of Cochrane Reviews – over 5,000 so far, published online in the Cochrane Database of Systematic Reviews.

5. http://www.cochrane.org/ “The Cochrane Collaboration is an enterprise that rivals the Human Genome Project in its potential implications for modern medicine." The Lancet 

6. Cochrane Stroke Group • Publishes systematic reviews of interventions for stroke • Established in 1993 • International editorial board, Co-ordinating Editor Peter Langhorne (University of Glasgow) • Hosted by University of Edinburgh

7. Edinburgh

8. Cochrane Stroke Group Register of Trials includes 19,000 publications from > 7,800 trials of interventions for treatment, rehabilitation and prevention of stroke World’s most comprehensive register of stroke trials 2012 1974 Year of publication

9. Impact of Cochrane Stroke Reviews • 171 reviews published in Cochrane Database of Systematic reviews (CDSR) • Many incorporated in national stroke guidelines around the world • CDSR has the highest journal impact factor of any stroke-specific journal 6.0 • Abstracts available free at http://www.cochrane.org

11. Haemodilution review (Chinese edition)

12. Present: which stroke treatments are effective?

13. S. AMERICA JAPAN Osaka Joinville 31 clinical trials (6900 participants)

14. Stroke unit studies in lower or middle income countries: Death at the end of follow up Langhorne et al. Lancet Neurol (2012)

15. Impact of stroke interventions in acute stroke Population of 1 million people (2500 new strokes per year) Additional independent survivors per year resulting from specific treatments Impact in Brazil Stroke unit (80%) 6000 rtPA (20%) 2500 Aspirin (80%) 1200 Langhorne et al. Lancet Neurol (2012)

16. Cost of disease and low cost of evidence-based prevention • Cost of event & care afterwards • Stroke $404–910 • Cost/year after stroke $408–775 • Costs / year of drug • Aspirin $2 • Enalapril $7 • Amlodipine $9 • Lovastatin $14

17. Present: which stroke treatments are NOT effective?

18. Cochrane reviews of agents shown to be ineffective in acute stroke

19. As many as 48% of stroke patients being referred to AIIMS are found to have been prescribed useless, expensive drugs at the hospitals where they have come from, says a random audit of 250 prescriptions. The audit, done by Professor Kameshwar Prasad in the Department of Neurology at AIIMS was presented at  the 8th World Stroke Congress in Brazil

20. Future: three steps to make sure the research addresses important questions

21. Step 1: Make knowledge accessible

22. Step 2: Identify uncertainties • The James Lind Alliance is a non-profit making initiative, with DORIS, it brought patients, carers and clinicians together to identify and prioritise the  top 10 uncertainties, or 'unanswered questions', about the effects of stroke rehabilitation • This information will help ensure that those who fund health research are aware of what matters to both patients and clinicians. Lancet Neurology 2012 : 11: 209

24. Step 3: collaborate with low-and middle-income countries

25. Country comparisons of human stroke research since 2001 • Per population, there was a negative association (r0.60) between burden of stroke (disability-adjusted life-years lost) and number of articles per population. • In China, South Korea, and Singapore, the annual growth of stroke articles was more than twice the worldwide average. • Multinational collaboration was common in Europe and North America, but was relatively uncommon between Asian countries. Asplund. Stroke. 2012;43:830-837

26. Map of Cochrane Collaboration centres

27. Brazilian Cochrane Centre • Secured free access to The Cochrane Library, throughout Latin America and the Caribbean, • The BCC has also provided research and training resources to more than 200 graduate students of health-related programs, 

28. Our vision: healthcare decision-making throughout the world informed by high-quality, timely research evidence “The Cochrane Collaboration has a special interest in involving people from all walks of life to participate in its activities and provides considerable support to enable this. This heady mix of social relevance, good science, altruism and global partnership makes The Cochrane Collaboration one of the most valuable and exciting enterprises in the world today.”  - Prathap Tharyan, Director of the South Asian Cochrane Centre, Vellore, India

29. Acknowledgements Cochrane Stroke Group: Peter Langhorne, Hazel Fraser, Brenda Thomas, Alison McInnes Alex Pollock (DORIS Group) Kameshwar Prasad Cochrane Stroke Editorial Board Charles Warlow, Sir Iain Chalmers, Carl Counsell, Mike Clarke, and numerous members of the Cochrane Collaboration

31. Extra slides

32. Map of international collaboration in clinical and epidemiological stroke research Asplund K et al. Stroke 2012;43:830-837

33. Observational studies of stroke unit implementation

34. Observational studies of stroke unit implementation Scandinavia UK Mediterranean W Europe Canada Australia

35. Map of international collaboration in clinical and epidemiological stroke research Asplund K et al. Stroke 2012;43:830-837

36. Years of life gained (millions) world-wide by an additional 2% annual reduction in stroke death rates, 2006–15 Lancet Neurology 2007; 6: 182-7

37. Trials of Hypertension Prevention (TOHP) phases I and II, Reduced incidence of CVD achieved by reduction of sodium intake by 33 - 44 mmol / 24 hours: Long-term follow-up 10-15 years after original trial CVD eventreduced by 30%, (95% CI 6-47%) adjusted for baseline Na+ excretion & weight. N = 744 pre- hypertensives Na+: 44 mmol / 24 h N = 2,382 Na+: 33 mmol / 24 h Cook NR et al. BMJ 2007;334:885-93

38. Non-personal interventions could avert 21 million DALY’s wordlwide • Salt reductions through voluntary agreements with food industry • Population-wide reduction in salt intake • Health education • Personal interventions for people at high absolute risk could avert 63 million DALY’s worldwide • Individual-based hypertension treatment • Individual-based treatment for high cholesterol • Absolute-risk approach (treatment if absolute risk of a vascular event over 10 few years > 35%) • Overall, the combination could avert 50% of theglobal burden of disease due to cardiovascular events Murray Lancet 2003: 371; 716-725

39. Journal impact factors CDSR Stroke 6.0 Stroke (AHA) 5.7 JCBFM 5.0 Cerebrovascular Diseases 2.7 International Journal of Stroke 2.4 Journal of Stroke & Cerebrov. Diseases 1.7 Topics in Stroke Rehabilitation 1.4

40. Stroke unit outcomes - death or institutional care Cumulative meta-analysis Regional results Stroke unit better Stroke unit better 1960 1970 1980 1990 2000 UK Scandinavia Mediterranean China Brazil Australia/NA High scanning rate Low scanning rate CT scanning rates .3 .5 1 2 5 .3 .5 1 2 5 SUTC (unpublished)