Evidence Based Stroke Update

2017

Ajay Bhalla

Guy’s and St Thomas’ Hospitals

UK Stroke Forum

Future is hard to predict…..

Future is hard to predict…..

Future is hard to predict…..

Future is hard to predict…..

Future is hard to predict…..

Lecture Outline

Early Rehabilitation

Secondary Prevention

Intra-arterial interventions

Organised stroke care

Optimal Head Position

What does the Guideline say?

Original Article

Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke

Craig S. Anderson, M.D., Ph.D., Hisatomi Arima, M.D., Ph.D., Pablo Lavados, M.D., M.P.H., Laurent Billot, M.Res., Maree L. Hackett, Ph.D., Verónica V. Olavarría, M.D., Paula Muñoz

Venturelli, M.D., Ph.D., Alejandro Brunser, M.D., Bin Peng, M.D., Liying Cui, M.D., Lily Song, M.D., Ph.D., Kris Rogers, M.Biostat., Ph.D., Sandy Middleton, Ph.D., Joyce Y. Lim, M.Nurs., Denise Forshaw, PG.Cert., C. Elizabeth Lightbody, Ph.D., Mark Woodward, Ph.D., Octavio Pontes-

Neto, M.D., H. Asita De Silva, D.Phil., Ruey-Tay Lin, M.D., Tsong-Hai Lee, M.D., Ph.D., Jeyaraj D. Pandian, D.M., Gillian E. Mead, M.D., Thompson Robinson, M.D., Caroline Watkins, Ph.D., for the

HeadPoST Investigators and Coordinators

Examine the effects of lying flat compared with sitting up head positioning in the first 24 hours of hospital admission for patients with acute stroke

N Engl J MedVolume 376(25):2437-2447

June 22, 2017

11

Anderson CS et al. N Engl J Med 2017;376:2437-2447

Characteristics of the 11,093 Patients with Acute Stroke at Baseline.

Intervention Effects in the Lying-Flat Group and the Sitting-Up Group at 90 Days, According to Modified Rankin Scale Score.

Anderson CS et al. N Engl J Med 2017;376:2437-2447

Odds ratio: 1.01; 95 CI: 0.92 to 1.10; P=0.84

Safety

14

Implications

• Question the generalisability (mild strokes,

presented late)

• No data on perfusion/penumbra size

• Patients with large vessel occlusion could

benefit from a positional strategy

• Perhaps individualised approach is required as

no clear benefit or harm

• Lying flat: is not harmful

• Guidelines need to reflect this.

Early Rehabilitation

Secondary Prevention

Intra-arterial interventions

Organised stroke care

PFO and Stroke

20-30% of ischaemic stroke: cryptogenic

Mechanism: Paradoxical Embolism

3 fold increase in recurrent stroke

PFO and Stroke

Negative Results

• Low event rate

• High risk patients not being randomised

• Definition of Cryptogenic stroke not

standardised

• Devices: older

• Follow up was short with few patients

• Not everyone had imaging

What does the Guidelines Say?

Original Article

Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke

Jeffrey L. Saver, M.D., John D. Carroll, M.D., David E. Thaler, M.D., Ph.D., Richard W. Smalling, M.D., Ph.D., Lee A. MacDonald, M.D., David S. Marks, M.D., David L.

Tirschwell, M.D., for the RESPECT Investigators

Patients who had a cryptogenic stroke and a PFO were randomly assigned to PFO closure (499) or medical therapy (481) with a median follow up (5.9 years)

Patients who had had a cryptogenic stroke and had a PFO were randomly assigned to medical therapy or PFO closurN Engl J Med

Volume 377(11):1022-1032September 14, 2017

Recurent ischaemic stroke: PFO 18 (3.6%) vs Medical 28 (5.8%)

NNT: 43 to prevent 1 recurrent stroke over 5 years

Rate of Recurrent Ischemic Stroke According to Subgroup.

Saver JL et al. N Engl J Med 2017;377:1022-1032

Serious Adverse Events Related to the Procedure or Device among the 499 Patients in the PFO Closure Group.

Saver JL et al. N Engl J Med 2017;377:1022-1032

Original Article

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

On behalf of CLOSE Investigators

Comparing PFO Closure after Cryptogenic stroke or antiplatelet vs anticoagulationIn patients with atrial septal aneurysm or large interatrial shunt (16-60 years old)

N Engl J MedVolume 377(11):1011-1021

September 14, 2017

Randomisation

1:1:1 randomisation with sub-groups if contra-indications to one modality

664 patients recruited 2008-2016

Kaplan-Meier Estimates

NNT: 20 to prevent 1 recurrent stroke over 5 years

Anti-coagulation vs Anti-platelets – 3 vs 7 events; p=0.44 (0.11-1.48 CI)

Adverse Events

10 of 11 device related AF cases were within 30 days of procedure

and did not recur in a median follow-up of 4.4 years

Procedural complication rate = 14 (5.9%)

Follow-up echocardiography (mean 10.8 months) – 93% had <10 microbubbles

Original Article

Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke

REDUCE Clinical Study Investigators

Comparing PFO closure (combined with antiplatelet therapy) vs antiplatelet therapy on the risk of recurrent stroke and new brain infarction (24 months): 664 patients

Kaplan-Meier Estimates

PFO Closure: 6 (1.4%) vs Antiplatelets 12 (5.4%)

NNT: 28 to prevent 1 recurrent stroke in 24 months

Adverse Events

Limitations

• Total number events were small

• Potential for bias for differential drop out

rates

• Generalisability due to concurrent closure

outside trial

• Absence of prolonged cardiac monitoring

Implications

• Not all patients with PFO require closure

• Stroke as a result of PFO is uncommon

• Thorough analysis of risk factors is required

prior to embarking on closure

• Potential benefit of closure is determined by

patient characteristics and anatomical

abnormalities of PFO

• Closure can be conducted with a high degree of

safety and efficacy in carefully select patients to

reduce stroke long term