1. EXERCISE AFTER STROKE Specialist Instructor Training Course L6 Exercise after stroke: theory and evidence

2. Overview of Session What is fitness training? How randomised controlled trials are designed Systematic review of fitness training after stroke (2004) STARTER Systematic review (2008) Contraindications to exercise training

3. Learning outcomes After this session you should be able to: Describe what is known, and what is not known about the effects of exercise on stroke recovery. Discuss the strengths and limitations of the evidence for exercise after stroke Explain how the STARTER trial informs the current course State the recommendations for exercise after stroke List the contra-indications for exercise after stroke

4. Physical Fitness A set of attributes which people have or achieve, that confers the ability to perform physical activity; Cardiorespiratory fitness (central and peripheral components) Muscular strength (maximum force that can be generated by A muscle) and muscle power (rate at which muscular force Can develop during a single muscle contraction) Body composition (relative amounts of muscle and adipose tissue)

5. Physical Fitness Training Planned, structured regimen of regular physical exercise deliberately performed to improve one or more components of physical fitness (UHDHHS 1996) Physical fitness training after stroke may, in theory –Improve function –Reduce disability –Improve quality of life –Improve mood –Reduce fatigue –Reduce the risk of falls –Improve vascular risk factors and so reduce risk of recurrent stroke and death

6. Design of a Randomised Controlled Trial Patients Baseline assessments Randomised ControlIntervention Assessments at end of interventions

7. Systematic reviews and meta-analyses Combines results of all trials of the same (or similar) intervention Provides a more precise measure of the effectiveness (and risk) of an intervention than a single trial Widely used to guide clinical practice

8. Cochrane Systematic Review Physical fitness training after stroke How? Extensive literature search and scrutiny of trials by 3 Reviewers We found; 12 trials (289 patients) BUT Only 4 trials (60 patients) used ‘mixed’ training Only 2 trials (33 patients) of adequate length to improve fitness Little information on feasibility More trials needed Saunders Greig Young Mead 2004

9. What has happened since 2004? More trials have been performed, including our own STARTER trial A further systematic review and meta-analysis has been performed to determine the effect of physical fitness training on –Death –Dependence –Death and dependence –Disability –Physical function, physical fitness –Mood, fatigue –Whether benefits are retained after training complete

10. Aims of STARTER Determine feasibility of physical fitness training after stroke Obtain data about the effect of physical fitness compared with an attention control intervention Use STARTER results to design a bigger trial

11. STARTER design Independently ambulatory, completed rehabilitation, no confusion or contraindications to exercise? Baseline assessments Randomised Fitness training Relaxation (both three times a week for 12 weeks) Repeat assessments at end of interventions and 4/12

12. Assessments Disability Nottingham extended ADL Functional independence measure Function Sit to stand Timed up and go Functional reach Elderly mobility scale Rivermead motor index Quality of life (SF-36) Mood (HADS) Physical fitness Comfortable walking velocity Walking economy Leg extensor power

13. Important baseline characteristics Exercise (n=32)Relaxation (n=34) Age (mean, SD)72 (10.4)71.7 (9.6%) Number (%) men18 (56)18 (53%) TACS PACS LACS POCS uncertain 1 16 10 4 1 16 9 8 0 Time between stroke and baseline (median, IQR) Median (IQR) FIM 171 (55-287) 117.5 (114-121) 147.5 (78.8-235.5) 117.5 (112.8-122)

14. Fitness training intervention Devised by a Clinical Exercise Instructor in collaboration with a Specialist Stroke Physiotherapist (Mark Smith) Progressive in duration and intensity Warm up and cool down Cycling, marching, stepping, staircase, ball raises, chest press Resistance band exercises, sit-to-stand, arm press

18. Relaxation (attention control) Same venue as exercise class Same instructor 3 times a week, 12 weeks Performed seated –Deep breathing –Progressive muscle relaxation (no muscle contraction) –During 12 weeks: progression

20. Feasibility: recruitment Ambulatory patients assessed (RIE, Liberton and AAH)301 Eligible 147 Agreed to take part 80 changed their minds-14 developed contraindications -11 died-1 Additional Recruitment (WGH)12 Total 66

21. Feasibility: attendance Median number of classes attended was –36 (IQR 30 to 36.75) for exercise –36 (IQR 30.5 to 37) for relaxation At post-intervention assessment –64 (97%) attended 1 st post-intervention assessment –62 (94%) attended 2 nd post-intervention assessment

22. Outcomes in exercise group Results are mean or median, * p<0.05 from baseline. No statistically significant changes in other variables Baseline1 st post- intervention 2 nd post- intervention Role physical (SF36)75.090.6*78.1 General health (SF-36)6272*63.5 Vitality (SF-36)53.058.9*55.3 Mental health (SF-36)7080*75 Role emotional (SF-36)87.5100*100 Functional reach (cm)24.528.5*26.5 Timed up-and-go (s)12.311.4*12.2 Sit to stand (s)1.490.95*1.11* Leg extensor power (affected leg) (w/kg) 1.011.19*1.18* Comfortable walking speed m/s0.660.73*0.70 Walking economy (VO2 ml/kg/m) 0.1280.126*0.127

23. Outcomes in relaxation group Mean or median, * p<0.05 from baseline. No statistically significant changes in other variables Baseline1 st post- intervention 2 nd post- intervention Mental health7080* Leg extensor power (unaffected leg) 1.121.26*1.27* Comfortable walking speed (m/s) 0.670.74*

24. Differences between groups 1 st post-intervention assessment Exercise better than relaxation Quality of life: role physical Physical function: timed up and go Physical fitness: walking economy 2 nd post-intervention assessment Exercise better than relaxation Quality of life: role physical

25. Qualitative sub-study (benefits) Enjoyment –The class itself –Socialising –Getting out of the house Tuition –Endless praise for Irene (the exercise instructor) –Participants felt ‘well looked-after’ –Irene had a major role in the success of the class

26. Qualitative sub-study (benefits) Perceived benefits from both classes: –Physical recovery –Getting back into a routine –Improved mood and wellbeing –Confidence Long term effects –Learning new skills –Practising at home –Attending other classes

27. To quote one participant……. It was back in November and it was no joke That was the time that I suffered a stroke…. Round came time for relaxation class Others were there who’d been in the same boat… The things we learned were useful and good…. The lady who ran the class is an excellent woman Her voice is gentle and booming…… Thanks to the excellence of the wonderful Irene

28. Conclusions Trial design was feasible Exercise was more beneficial than relaxation for some outcomes Not all benefits were maintained long-term These results are included in the updated Cochrane systematic review and meta- analysis

29. Physical Fitness Training for Stroke Patients Protocol first published: Cochrane Library, Issue 4, 2001 Review first published: Cochrane Library, Issue 1, 2004 Review updated: Cochrane Library, Issue 4, 2009 Cochrane Library, Issue 4, 2011 Cochrane Library, Issue 4, 2013

30. Systematic Review Literature Search Screened N=7508 RCTs included N=45 n=2188 Not relevant N=7433 Cardio N=22 n=995 Resistance N=8 n=275 Mixed N=15 n=918 MEDLINE, EMBASE, CINAHL, SPORTDiscuss electronic databases Hand searching Pending references Other databases and websites 13 new trials + 32 previously included Excluded N=29 RCTs Ongoing N=16 Cannot be classified N=17

31. Number of patients randomised in trials of physical fitness training after stroke Research in exercise after stroke is increasing…

32. Trial participants Average age 64 years (i.e. younger than the median age of stroke onset of 72) 60% men, 40% women Majority were ambulatory Time since stroke: 8.8 days to 7.7 years

33. Primary Effects of training on death & dependence unclear Exercise improves of disability Secondary Exercise improves physical fitness Exercise improves walking Exercise improves balance Other benefits unclear Results Primary & Secondary Outcomes

34. Results Secondary Outcome Measures OutcomeCardioStrengthMixed Adverse events??? Physical fitness  VO 2  Strength ? Walking  ns  Function  Balance ?? Quality of life??? Mood???

35. Results Maximum walking speed (5-10 metres) Cycle Ergometer Treadmill Treadmill – backward walking Treadmill – forward walking Treadmill Over-ground walking Circuit training including walking Treadmill Treadmill + over-ground walking + 7.37 m/min 95%CI [3.70 to 11.03]

36. InterventionWalking Outcome End of interventionEnd of follow-up N (n)Mean Difference (95% CI)Sig.N (n)Mean Difference (95% CI)Sig. Cardio Training MWS 13 (609)7.37 m/min (3.70, 11.03)P < 0.00015 (312)6.71 m/min (2.40, 11.02)P = 0.002 PWS 8 (425)4.63 m/min (1.84, 7.43)P = 0.0012 (126)0.72 m/min (-6.78, 8.22)NS 6-MWT 10 (468)26.99 metres (9.13, 44.84)P = 0.0034 (233)33.37 metres (-8.25, 74.99)NS Resistance Training MWS 4 (104)1.92 m/min (-3.50 to 7.35)NS1 (24)-19.8 m/min (-95.77, 56.17)NS PWS 3 (80)2.34 m/min (-6.77 to 11.45)NS--- 6-MWT 2 (66)3.78 metres (-68.56 to 76.11)NS1 (24)11.0 m/min (-105.95, 127.95)NS Mixed Training MWS------ PWS 9 (639)4.54 m/min (0.95 to 8.14)P = 0.014 (443)1.60 m/min (-5.62, 8.82)NS 6-MWT 7 (561)41.60 metres (25.25 to 57.95)P < 0.000013 (365)51.62 metres (25.20, 78.03)P = 0.0001 Results More Walking Performance Outcomes

37. Conclusions Physical fitness training after stroke Training improves disability, physical fitness, walking performance & balance Benefits are confined to cardiorespiratory and mixed training Benefits are exercise-specific Further research is required (e.g. optimal ‘prescription’, long-term benefits, risks, costs, non- ambulatory patients)

38. What we don’t know Effect of fitness training on many important outcomes e.g. mood, fatigue, falls, disability, dependence and death Effect on vascular risk factors Optimum type of training Optimum mode, frequency, intensity, duration Timing (e.g. in-patient, after usual rehab) Whether any benefits are retained longer-term Feasibility of exercise delivery to non-ambulatory patients Might some benefits be mediated by social interaction? How to ensure people continue exercise after initial training programme

39. Implications for exercise classes after stroke Exercise training may improve walking ability if cardiorespiratory training is included Disability may be improved by cardiorespiratory training or mixed training Effects of strength training alone are uncertain Further research is needed

40. Absolute contraindications to exercise training Uncontrolled angina Recent myocardial infarction Resting systolic blood pressure >180 mmHg or resting diastolic BP of >100mm Hg Significant drop in BP during exercise Uncontrolled resting tachycardia >100 beats per minute Unstable or acute heart failure New or uncontrolled arrhythmia Severe stenotic or regurgitant valvular heart disease Hypertrophic obstructive cardiomyopathy Third degree heart block Acute aortic dissection Acute myocarditis or pericarditis Unstable diabetes Uncontrolled visual or vestibular disturbances Recent injurious fall without medical assessment Proven inability to comply with the recommended adaptations to the exercise programme and inability to maintain an upright posture in sitting Febrile illness Extreme obesity, with weight exceeding the recommendations or the equipment capacity (usually >159kg [350 lb.]) Acute pulmonary embolus or pulmonary infarction Deep venous thrombosis

41. Relative contraindications Cardiomyopathy Moderate stenotic valvular heart disease Complex ventricular ectopy Left main coronary artery stenosis Electrolyte imbalance Tachyarrhythmias or bradyarrhythmias High degree atrio-ventricular block Mental or physical impairment leading to inability to exercise adequately

42. Acknowledgements Dr Dave Saunders, Lecturer, University of Edinburgh Dr Carolyn Greig, Senior Research Fellow, University of Edinburgh Professor Archie Young, Emeritus Professor, University of Edinburgh Hazel Fraser and Brenda Thomas Cochrane Stroke Group http://www.dcn.ed.ac.uk/csrg http://www.dcn.ed.ac.uk/csrg

43. Essential Reading Further detail about the topics discussed in this session can be found in section L6 of the course syllabus.