From Negligence to Excellence…. Curing tobacco addiction in hospitalised sick smokers

1. From Negligence to Excellence….Curing tobacco addiction in hospitalised sick smokers Dr Matthew Evison Consultant in Respiratory Medicine, Manchester University NHS Foundation Trust Director of the Lung Pathway Board Greater Manchester Cancer Clinical Lead for the CURE Programme, Greater Manchester

2. Global Scale of the Tragedy • Smoking is the single greatest cause of preventable death, disability, ill-health and social inequality • Tobacco will kill over 175 million people between now and the year 2030 • 600,000 non-smokers die each year from second hand smoke, 28% of which are children • Half of all smokers will die prematurely & loose an average of 10 years of life • After the age of 35 smokers loose a day of life for every 4 days of smoking • Smoking causes 16 different forms of cancer and damages every organ in the body “Tobacco is the most effective agent of death ever developed and deployed on a worldwide scale”  American Cancer Society CEO

3. UK Scale of the Tragedy • There are nearly 8 million smokers in the UK (5% currently access to stop smoking services) • Recent decline in smoking prevalence in the general population is due to reduce uptake • Most immediate tobacco control imperative is helping active smokers to quit • Smoking costs the NHS: £850 million per year inpatient costs, £1.1 billion per year in primary care costs and £696 million per year in OP secondary care services • Treating tobacco addiction is the single most cost-effective life saving intervention provided by the NHS • The cost per life year gained of treating tobacco addiction is 1/25th the cost of statin therapy in patients with coronary artery disease

4. Lets look at some definitions “An abnormal condition of a body part, an organ, or a system resulting from various causes, such as infection, genetic defect, or environmental stress, and characterized by an identifiable group of signs or symptoms.” To provide equal & fair access to all patients to the most effective & evidence based treatments for their illness and disease, physical or mental What is a disease? What is the purpose of the NHS?

5. Tobacco Addiction • Symptoms of withdrawal: • Restlessness • Agitation • Sweating • Nausea • Headaches • Insomnia • Poor concentration • Anxiety • Anger • Irritability Environmental stress: ‘The Trigger’ Tobacco addiction is a disease A chronic & relapsing disease that often begins in childhood Pathological condition: ‘Abnormal change in structure or function’ Identifiable group of symptoms

6. Nicotine is a relatively harmless drug Highly addictive in the brain but otherwise very similar to caffeine • NICE PH45 • Nicotine causes: • Noincrease in serious adverse events • Noincrease cardiovascular events • Noincrease in cancer • Noincrease in mortality • Adverse events common but not severe

9. 14750 admissions from 146 hospitals • 73% had smoking status documented • 28% smokers asked if they want to stop • 6% of smokers referred to smoking cessation services • 4% of smokers prescribed Nicotine replacement therapy • Virtually 0% prescribed Varenicline (Champix) • 51 of hospitals have a smoking cessation practitioner • 23% of hospitals able to prescribe pharmacotherapy for tobacco addiction • 26% of hospitals have a consultant lead for smoking cessation • 44% of hospitals offer training to frontline staff

10. 20,000 smokers in hospital on any given day in the UK 1 million smokers admitted to hospital at least once each yr Smokers are 36% more likely to be admitted to hospital Secondary Care • Perceived vulnerability • Fear for future • Realisation of impact • Link illness to smoking • Forced abstinence • Removed from normal home and habits • Intensive motivational interviewing • Immediate feedback • Monitoring • Compliance • Education

11. Ottawa model of smoking cessation The systematic identification and documentation of all smokers admitted to hospital The systematic administration of pharmacotherapy & behavioural support to active smokers in hospital The systematic attachment to long term community follow-up services after discharge The 5As: Ask, Advise, Assess, Assist, Arrange

12. Ottawa model of smoking cessation Mortality halved by 1 year 11.4%vs5.4%; p<0.001 Mortality reduction at 2 years 15.1%vs7.9%; p<0.001 Increase quit rates at 6 months 35% vs 20% Re-admission halved by 30 days 13.3%vs7.1%; p<0.001 Re-admission reduced at 1 year 38.4%vs 26.7%; p<0.001 Effectiveness of a hospital-initiated smoking cessation programme: 2-year health and healthcare outcomes. Mullen et al Tob Control 2016;0:1–7. doi:10.1136/tobaccocontrol-2015-052728

13. Applying the Ottawa Model to Greater Manchester: Key benefits and outcomes Conservative estimation of 263,900 adult admissions to hospital across GM per Assuming 20% were active smokers = 52,780 smokers. • 3273 readmissions prevented at 30 days • 6176 readmissions prevented at 1 year • 3141 lives saved in 1 year • 18,473 successful quitters in the first year The 2015 Department of Health Reference Costs state an average non-elective hospital admission costs £1609. Therefore, the estimated savings from prevention of readmissions by applying the Ottawa Model to Greater Manchester is therefore £9,937,184 per year. The average length of hospital stay in England is 5 days (NGS Digital Data 2015-2016. The CURE project is estimated to save 30,880 bed bays per year, equivalent to 84 additional beds per day across Greater Manchester

14. Pharmacotherapy for tobacco addiction The evidence-base

15. Nicotine Replacement Therapy • Nicotine absorbed through the buccal membrane (short acting) or skin (long acting) • Reduces carvings through binding to nicotinic receptors and dopamine release • De-sensitisation of nicotinic receptors through slower release nicotine • Breaking the association of smoking and craving relief – the habit

16. Nicotine Replacement Therapy • Nicotine replacement therapy is an effective treatment for tobacco addiction increasing the chance of abstinence by approximately 60% compared to placebo (RR 1.60 95%CI 1.53-1.68) Cochrane Review 2012, 117 trials, Stead et al • Adding NRT to behavioural support in hospitalised smokers increases abstinence by approximately 60% (HR 1.54 95%CI 1.34-1.79) Cochrane Review 2012, 6 trials, Rigotti et al • NRT is cost-effective even when modelling at the lowest quit rate (9%) and most expensive NRT (£763 per person). Cost per QALY £634 (NICE threshold £30,000) 2018 NICE PHG94

17. Varenicline binds with high affinity and selectivity at the α4β2 neuronal nicotinic acetylcholine receptor, where it acts as a partial agonist. Its binding both: • Alleviates symptoms of craving and withdrawal • Reduces the rewarding and reinforcing effects of smoking by preventing nicotine binding to α4β2 receptors.

18. Bupropion for smoking cessation

19. 2007 2x RCTs compared varenicline, bupropion and placebo (n = 1483 and 1413). 1x RCT Varenicline vs placebo (n = 2416). 9–52 week quit significantly greater for varenicline compared with bupropion OR 1.46 (95% CI 0.99 to 2.17) OR 1.77 (95% CI 1.19 to 2.63). Meta-analysis (indirect comparison) of 70 NRT trials, 12 bupropion trials and 4 varenicline trials against control/placebo. At 12 months varenicline was superior to: NRT (OR 1.66 [CI 1.17 to 2.36]) Bupropion (OR 1.58 [95% CI 1.22 – 2.05]) Continuous quit rate for varenicline was statistically significantly greater than for placebo OR 3.85 (95% CI 2.70 to 5.50) OR 3.85 (95% CI 2.69 to 5.50) 9–12 week quit rate significantly greater for varenicline vs bupropion OR 1.93 (95% CI 1.40 to 2.68) OR 1.90 (95% CI 1.40 to 2.68)

20. Varenicline for smoking cessation Conclusions: Varenicline is superior to NRT and bupropion in achieving continuous abstinence (Over a lifetime horizon varenicline dominated bupropion and NRT – it was cheaper and more effective - in all sensitivity analysis).  Varenicline should normally be provided in conjunction with counselling and support, but that if such support is refused or is not available, this should not preclude treatment with varenicline. When NICE recommends a treatment 'as an option', the NHS must make sure it is available. This means that, if the doctor responsible for a patient's care thinks that varenicline is the right treatment for smoking cessation, it should be available for use, in line with NICE's recommendations.

21. West R, Owen L (2012) Estimates of 52-week continuous abstinence rates following selected smoking cessation interventions in England. www.smokinginengland.info

22. Estimated 52 week abstinence Uptake as % smokers Cost per treatment 0.5% of £8,000,000 smokers = 40,000 smokers = 9,600 quitters 2.8% of £8,000,000 smokers = 224,000 smokers = 26,880 quitters

23. Post 2007 NICE Appraisal Evidence • Varenicline is an effective treatment for tobacco addiction increasing the chance of abstinence by over 200% versus placebo (RR 2.24 95%CI 2.06-2.43) • Cochrane Review 2013, 27 trials, 12,625 patients, Cahill et al • Varenicline is more effective than bupropion. Smokers are approximately 40% more likely to stop with varenicline versus bupropion (RR 1.39 95%CI 1.25-1.54) • Cochrane Review 2013, 5 trials, 5877 patients, Cahill et al • Varenicline and behavioural support is the most effective combination to treat tobacco addiction in meta-analysis of 115 trials and 57,000 patients. Smokers are approximately 60% more likely to stop smoking with varenicline and behavioural support than with bupropion (OR 1.56 95%CI 1.07-2.34) and NRT (OR 1.65 95%CI 1.10-2.12) • Windle et al. Am J Prev Med 2016

24. 2012 146 RCTs 65 standard-doses of the nicotine patch (≤ 22 mg) 6 high-dose NRT patch (> 22 mg) 5 high versus standard-dose NRT patch 5 combination NRT versus inert controls 6 combination versus single NRT patch 48 bupropion 11 varenicline Conclusions. All pharmacologic treatments were significantly more effective than inert controls. Varenicline was the only treatment demonstrating effects over other options.

25. Cochrane Database of Systematic Reviews 2016 • RCTs with minimum 6 month follow-up • Number Needed to Treat (NNT) derived from pooled difference between placebo and treatment quit rates

26. Safety – Cardiovascular events • No increase in cardiovascular events with varenicline in a systematic review of 38 trials (RR 1.03 95%CI 0.72-1.49) • Sterling et al. J Am Heart Assoc 2016 • No increased risk of cardiovascular events with varenicline in a study of 14,350 patients with COPD • Kotz et al. Thorax 2017 • NRT is safe in stable and unstable cardiovascular disease • NICE PH48 • Safety – Neuropsychiatric adverse events • No increase in neuropsychiatric adverse events from pharmacotherapy for tobacco addiction in network meta-analysis • Roberts et al. Addiction 2016

27. A multicenter, randomized, double-blind, placebo-controlled trial of varenicline for smoking cessation in patients with stable CVD 39 sites in 15 countries 2006-2008 Varenicline vs placebo for 12 weeks & 52 week blinded Follow up 714 patients 2010 No difference in the rate of cardiovascular, cerebrovascular or peripheral vascular events or deaths Varenicline is effective for smoking cessation in smokers with cardiovascular disease

28. Multi-centre, double-blind, randomized, placebo-controlled trial Smokers hospitalized with an ACS Varenicline vs placebo for 12 weeks. All patients received low-intensity counselling.  302 pts randomised 2016 Counselling involved advice to stop smoking and additional counselling was given by research personnel Major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%

29. 2013 525 smokers 38 centres in 8 countries 12 weeks varenicline vs placebo 40 week non-treatment follow-up CO-validated quit rates 9-12 weeks 75% taking anti-depressant medication

30. 2015

32. Largest trial of smoking cessation pharmacotherapy Study requested and co-designed with the FDA 140 centres, 16 countries, 5 continents Double-blind, triple dummy, placebo controlled, randomised trial Smokers aged 18-75, at least 10 cpd 12 weeks of treatment + 12 weeks of further FU (24 week trial) Total 15 clinic visits – 10 minutes of smoking cessation advice 8144 participants randomised

33. Neuropsychiatric safety outcomes Psychiatric vs non psychiatric cohorts Psychiatric illness stable for 3 months – no medication changes Psychiatric illness stratified as mood, anxiety, psychotic, personality Clearly defined composite outcome – 16 neuropsychiatric symptoms ‘Neuropsychiatric adverse event Interview’ – 25 questions Healthcare professional interview if ‘Yes’ to any question 8000 patients to estimate a 75% increase in neuropsychiatric adverse event rate within +1·59% or –1·59%

34. The average total HADS score improved from baseline through the treatment phase by about 2 points in the non-psychiatric cohort and 3 points in the psychiatric cohort, an effect that was similar across the treatment groups

35. Neuropsychiatric Adverse Events There is no increased risk of moderate to severe neuropsychiatric adverse events with varenicline (EAGLES study 2016, The Lancet). The act of stopping smoking carries a small risk of moderate to severe neuropsychiatric events and this is regardless of the treatment used. The risk is higher in those with a history of psychiatric illness (5%) versus those without (2%). Advise patients to seek help in the event of a neuropsychiatric event. In the long term, stopping smoking improves mental health disease, e.g. stopping smoking is more effective than antidepressants in treating depression.

37. The cure project

38. Past Future Changing the stigma & the culture Negative message You must stop Will power Motivation Your fault if you fail Choice Nicotine is dangerous Lifestyle choice Behavioural change Someone else’s role to help Positive message Physical disease Chemical dependence False pleasure / desire Nicotine is harmless Treatments work Never give up on giving up Chronic disease management Every clinicians role to treat tobacco addiction

40. Active smoker admitted to Wythenshawe Hospital • Admitting team identify smoking status and provide brief advice (C) • Automated electronic referral to the CURE team – opt-out service • Admitting team assess the level of tobacco addiction (U) • Admitting immediately commences NRT according to level of addiction and CURE protocol (R) Mandatory training modules • Specialist assessment by the CURE team (E) • Behavioural change support & motivational interviewing (40 min consultation) • Signposting and patient information • Offer & commence varenicline (bupropion in rare circumstances) • Discharged from hospital • 1 week of discharge medications • Telephone FU at 1-2 weeks • Clinic FU at 4 weeks with CO confirmed quit rate • Telephone clinic FU at 12 weeks • Discharged back to primary care

41. The CURE team want to see every smoker admitted to Wythenshawe Hospital before they go home. We are dependant upon nursing staff completing the Non-elective Nursing Admission Document in EPR

48. Side effects of medications

49. What is my advice to you?

50. What is my advice to you? Recognise the failings of our health services to treat the most deadly disease in the communities we serve: collective responsibility Change the stigma Smoking Cessation = tobacco addiction Lifestyle choice = disease Take responsibility for managing this disease Correct the failings of the past Use CURE toolkit, training, pathways, protocols www.thecureproject.co.uk Break down the barriers Bring tobacco addiction treatment back into NHS patient services