Evidence-based stroke medicine, past present and

future

Peter Sandercock

University of Edinburgh, UK

WSC, BrasiliaPresidential Lecture13th October 2012

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

Past: work done so far on building the evidence base

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.

“The Cochrane Collaboration is an enterprise that rivals the Human Genome Project in its potential implications for modern medicine."

The Lancet 

http://www.cochrane.org/

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

Edinburgh

Cochrane Stroke Group Register of Trials includes 19,000 publications from > 7,800 trials of interventions for treatment, rehabilitation and prevention of stroke

1974 Year of publication 2012

World’s most comprehensive register

of stroke trials

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

Haemodilution review (Chinese edition)

Present: which stroke treatments are effective?

S. AMERICAS. AMERICA JoinvilleJoinville

JAPANJAPANOsakaOsaka

31 clinical trials(6900 participants)

Langhorne et al. Lancet Neurol (2012)

Stroke unit studies in lower or middle income countries: Death at the end of follow up

Impact of stroke interventions in acute strokePopulation of 1 million people (2500 new strokes per year)

Additional independent survivors per year resulting from specific treatments

Langhorne et al. Lancet Neurol (2012)

Impact in BrazilStroke unit (80%) 6000rtPA (20%) 2500Aspirin (80%) 1200

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

Present: which stroke treatments are NOT effective?

Cochrane reviews of agents shown to be ineffective in acute stroke

Agent Number of trials

No. included patients

Vinpocetine 2 70

Glycerol 10 945

Piracetam 3 1002

Cerebrolysin 2 1215

Haemodilution 14 2631

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

Future: three steps to make sure the research addresses

important questions

Step 1: Make knowledge accessible

• 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.

Step 2: Identify uncertainties

Lancet Neurology 2012 : 11: 209

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

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

Map of Cochrane Collaboration centres

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, 

“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

Our vision: healthcare decision-making throughout the world informed by high-

quality, timely research evidence

AcknowledgementsCochrane Stroke Group:

Peter Langhorne, Hazel Fraser, Brenda Thomas,

Alison McInnesAlex Pollock (DORIS Group)

Kameshwar PrasadCochrane Stroke Editorial Board

Charles Warlow, Sir Iain Chalmers, Carl Counsell, Mike Clarke, and numerous

members of the Cochrane Collaboration

Extra slides

Map of international collaboration in clinical and epidemiological stroke research

Asplund K et al. Stroke 2012;43:830-837

Observational studies of stroke unit implementation

Observational studies of stroke unit implementation

Scandinavia

W Europe

Mediterranean

Australia

Canada

UK

Map of international collaboration in clinical and epidemiological stroke research

Asplund K et al. Stroke 2012;43:830-837

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

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:

Cook NR et al. BMJ 2007;334:885-93

N = 744 pre- hypertensivesNa+ : 44 mmol / 24 h

N = 2,382Na+ : 33 mmol / 24 h

Long-term follow-up 10-15 yearsafter original trial

CVD event reduced by 30%, (95% CI 6-47%) adjusted for baseline Na+ excretion & weight.

• 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 the global burden of disease due to cardiovascular events

Murray Lancet 2003: 371; 716-725

Journal impact factors

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

Stroke unit outcomes - death or institutional care

.3 .5 1 2 5

1960

1970

1980

1990

2000

.3 .5 1 2 5

UK

Scandinavia

Mediterranean

China

Brazil

Australia/NA

High scanning rate

Low scanning rate

CT scanning rates

Stroke unit better Stroke unit better

Cumulative meta-analysis Regional results

SUTC (unpublished)