Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation

Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation
Katherine Anderson, PharmD, Cash Wise Clinic Pharmacy/Carris Health

Background: Tobacco consumption in the U.S. is the leading cause of preventable morbidity and mortality. With more than 480,000 deaths and more than 34% of all cancer deaths annually. Racial/ethnic differences in quitting are not well understood. Non-Hispanic Black individuals (referred to as Black) have a prevalence of smoking that is comparable to non-Hispanic White individuals (White), smoke fewer cigarettes per day, smoke fewer days per month, but have higher rates of smoking related morbidity and mortality. Results of randomized clinical trials (RCTs) have shown mixed results with about half showing no difference in cessation rates between Black and White smokers, half showing higher cessation rates with White smokers, and only one study showing a higher cessation rates for Black smokers. Though no study has examined the variables with race and smoking cessation. Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) is the largest and most comprehensive smoking cessation study to date. The study found that Black smokers were significantly less likely than White smokers to quit across all treatments, but did not explore the reason for this difference. A secondary analysis of the EAGLES trial was designed to examine why Black smokers achieved lower quit rates compared to White smokers when given the same treatment and smoking cessation counseling. 

Methods: EAGLES was a randomized 1:1:1, double-blind, triple-dummy, placebo-controlled and active controlled (Nicotine Replacement Therapy (NRT): 21 mg per day with taper), varenicline (1 mg twice daily), bupropion (150 mg twice daily for 12 weeks with 12-week no treatment follow up. The trial recruited from 16 countries including the U.S. from November 2011-January 2015. A total of 8,144 male and female smokers aged 18-75 years with or without prespecified current or lifetime psychiatric diagnoses and who smoked 10 or more cigarettes per day were included. The study analyzed total participants and divided the results into participants with psychiatric conditions and non psychiatric conditions. Of the participants, 95.9% were either self-identified as Black or White and 53.2% of participants were from the U.S. (71.5% White vs. 25.0% Black participants compared to non-U.S. of 92.8% White vs 2.5% Black). Continued cigarette abstinence rate (CAR) for 9-24 weeks was the primary endpoint because longer periods of abstinence are more strongly associated with lifetime abstinence. Statistical analyses were performed using SAS statistical software version. Tests and 95% CI’s are 2-sides and used a 5% level of significance, which invoked a nominal P<0.1 rule. 

Results: The study included 1,065 U.S. Black participants (255 varenicline, 259 bupropion, 286 NRT, and 265 placebo) and 3,044 U.S. White participants (788 varenicline, 769 bupropion, 738 NRT and 759 placebo). Nine hundred and ninety-eight participants discontinued from the study after starting treatment. Only treatment and race were associated with CAR for weeks 9-24; 12.5% for White participants and 7.0% for Black participants. The absolute difference in CAR for weeks 9-12 was 6.6% less for Black vs. White participants [95% CI 0.45 - 0.69; P<0.01]. Comparing the relative efficacy of treatments with race, White smokers had a significantly higher odds of CAR with varenicline compared to bupropion. Black participants showed higher odds of continuous abstinence rates using a smoking cessation agent compared to placebo. There was no significant difference when compared to varenicline vs. bupropion or NRT, bupropion and NRT vs. placebo and bupropion vs. NRT for Blacks. Post baseline differences demonstrated that Black participants were less likely to discontinue treatment, had greater compliance, increased days of exposure to the drug studied, had greater reduction in depression, and fewer psychiatric and non psychiatric adverse effects over the study period. 

Discussion: This study does confirm prior Black-White differences in abstinence reported in RCTs. Black participants were significantly less likely to quit overall though differences do not appear to be from a pharmacological interaction. Socioeconomic variables were not measured in the EAGLES trial and cannot be speculated about that impact. All smoking cessation therapy had a greater efficacy compared to placebo for White smokers. Varenicline had greater efficacy compared to placebo but not other therapies for Black smokers. Lower rates of abstinence is likely due to inclusion of a large psychiatric cohort, lower-intensity behavioral counseling, and the use of more stringent continuous abstinence.  

Clinical Impact: The EAGLES study suggests that varenicline is the most successful smoking cessation agent regardless of race and Black smokers are less likely to quit than White smokers. Clinicians need to be aware that race is a proxy for powerful social and contextual factors that affect all aspects of life. Further studies should be conducted to examine the variables associated such as socioeconomic and biologic variables for Black smokers. In practice, clinicians shall consider all smoking cessation therapies, and select an agent for the patient that is best suited to help them successfully quit with minimal adverse events.



  1.  Nollen NL, Ahluwalia JS, Sanderson Cox L, Okuyemi K, Lawrence D, Samuels L, Benowitz NL. Assessment of racial differences in pharmacotherapy efficacy for smoking cessation. JAMA Network Open. 2021;4(1). doi:10.1001/jamanetworkopen.2020.32053