1. Journal Club Sidharth Bagga MD

2. Cytisus laborium L. (Golden rain acacia)

3. Case  CC: “ I’d like to quit, but it is cheaper to keep smoking ”  56 male with 20 pack year smoking history Seen in clinic in follow up Has had 4 unsuccessful attempts at quitting smoking Hx of HTN Patient is a construction worker and not very eager to spend his beer money on smoking cessation treatment anymore So what do you do now?  1. Smoking cessation tricks (impotence, wrinkles, etc)  2. Ask, document and move on  3. Varencycline  4. Nicotine replacement  5. New non approved Cytisine

4. Background / Context?  Smoking Prevalence 1960s – 42% to 2010s – 20%  Tobacco use remains chief avoidable cause of death in US Many clinicians do not offer smoking cessation Only 20% of smokers are ready to attempt quit at any time 95% of unaided attempts fail Pts typically consume 50% of recommended dose of medications Only complete about half of smoking cessation counseling  Treatment availability / ease of use? If treatment delayed or separate location, only 10% follow through If same location and immediate, 1/3 rd follow through Schweikert et al, Lancet, 2009

5. Cytisine Nicotine

6. Journal Club

7. Research Question Assess Cytisine’s  efficacy and safety in a context that could be replicated globally  relatively short treatment goal (25 days)  minimal contact with health professionals.

8. Design / Subjects  Prospective, randomized, single center, double- blind trial between 12/2007 & 9/2010 in Poland.  Inclusion Criteria Adults smoke > 10 cigs/day + willing to stop permanently, literate, provide consent  Exclusion Criteria Pregnancy, breast feeding, current psychiatric d/o, medical contraindication for Cytisine (arterial HTN + advanced arteriosclerosis)  Sampling No other smoking cessation drugs current Relapse: > 5 cigs used since enrollment, no smoking in last week, breath CO < 10ppm

9. Study Procedures  Variable block randomization (eliminates early/late bias)  First Visit Age, sex, employment, marital status, Nicotine Dependence (FTND), # of cigs/day, duration of smoking, & quit attempts Beck Depression Inventory  6 months Phone contacts If abstinent: return to clinic, CO in exhaled breath, Depression  12 months (same)  Adverse Reactions Asked, if ‘Yes’ then verbatim copied and compiled according to standard adverse reaction data

10. Measurements - Outcomes  Primary Outcome 12 month of abstinence from smoking Changed from original 6 months before unblinding/data analysis  Secondary Outcome Abstinence at 6 months and point prevalence at 12 months (week before visit)  Criteria for abstinence Fewer than 5 cig in last 6 months Confirmed with less than 10 ppm of CO in exhaled breath

11. Statistical Analysis  Sample Size Calculated need for 740 pts to show a difference of 6 points b/w groups to show percentage reduction in abstinence with 80% power & p <.05  Intention to treat analysis Categorical variables – x 2 and Fischer Exact test Logistic regression to examine efficacy with adjustment from baseline characteristics P <.05 was considered statistically significant

12. Study Enrollment & Follow Up

13. Baseline Characteristics

14. Cytisine administration 6 tabs/day 5 tabs/day 4 tabs/day 3 tabs/day 2 tabs/day DAY 1-3DAY 4-12DAY 13-16DAY 17-20DAY 20-25 QUIT DATE Total: 101 tablets

15. Study Procedures

16. Results

17. Adverse Events

18. Discussion  Evidence of efficacy of Cytisine as an aid in smoking cessation More gastrointestinal adverse events Rate of discontinuation / dose reduction (same as placebo)  Relative Rate Cytisine (3.4) higher than Varenicline (2.3) & Nicotine (1.6)  Absolute rate of Abstinence Lower than varenicline, but similar to nicotine replacement  Treatment period (4, 6, 8, 12 weeks)  May reduce cravings & make cigs less satisfying, like Varenicline (a2b4 receptor)

19. Limitations  Adults with previous attempts? Which medications?  Outcomes at 12 weeks? Standard for other drug regimens  Need to compare to current standard of care

20. Conclusion  Cytisine needs FDA approval  Studies to assess efficacy in conjunction with cognitive feedback  Cheap, effective alternative

21. JAMA Article Assesment: Therapy  Are the results of the study valid? Was the assignment of patients to treatments randomized? Yes Were all pts who entered the trial properly accounted for and attributed at its conclusion? Yes Was follow-up complete? Yes Were pts analyzed in the groups to which they were randomized? Yes Were patients, health workers, and study personnel blind to treatment? Yes Were the groups similar at the start of the trial? Yes Aside from the experimental intervention, were the groups treated equally? Yes

22.  What were the results? How large was the treatment effect? How precise was the estimate of the treatment effect?  Will the results help me in caring for my patients? Can the results be applied to my patient care? Yes (bulgarian drugs) Were all clinically important outcomes considered? SOME Are the likely treatment benefits worth the potential harms and costs? Yes JAMA Article Assesment: Therapy