Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation: Secondary Analysis of the EAGLES Randomized Clinical Trial.

Importance: Understanding Black vs White differences in pharmacotherapy efficacy and the underlying reasons is critically important to reducing tobacco-related health disparities. Objective: To compare pharmacotherapy efficacy and examine variables to explain Black vs White differences in smoking abstinence. Design, Setting, and Participants: This study is a secondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) double-blind, placebo-controlled, randomized clinical trial, which took place at clinical trial centers, academic centers, and outpatient clinics in 29 states in the US. US Black and White smokers who smoked 10 or more cigarettes per day with and without psychiatric comorbidity were enrolled between November 2011 and January 2015. Data analysis was performed from July 2019 to January 2020. Interventions: Participants were randomized (1:1:1:1) in a double-blind, triple-dummy, placebo- and active-controlled (nicotine patch) trial of varenicline and bupropion for 12 weeks with follow-up through week 24. Main Outcomes and Measures: Biochemically verified continuous cigarette abstinence rate (CAR) from weeks 9 to 24. Baseline, postbaseline treatment, and safety characteristics were examined as variables to explain race differences in abstinence. Results: Of the 1065 Black smokers enrolled, 255 were randomized to receive varenicline, 259 received bupropion, 286 received nicotine replacement therapy (NRT [ie, nicotine patch]), and 265 received placebo. Among the 3044 White smokers enrolled, 778 were randomized to receive varenicline, 769 received bupropion, 738 received NRT, and 759 received placebo. Participants were predominantly female (614 Black [57.7%] and 1786 White [58.7%] women) and heavy smokers (mean [SD] cigarettes per day, 18.2 [7.9] for Black and 20.0 [7.5] for White smokers), with a mean (SD) age of 47.2 (11.2) years for Black and 46.5 (12.7) years for White participants. Treatment and race were associated with CAR for weeks 9 to 24. The CAR was 4.9% lower for Black vs White participants (odds ratio [OR], 0.53; 95% CI, 0.41-0.69; P < .001); differences were found across all treatments. Pooling psychiatric and nonpsychiatric cohorts, varenicline (OR, 2.63; 95% CI, 1.90-3.63; P < .001), bupropion (OR, 1.75; 95% CI, 1.25-2.46; P = .001), and NRT (OR, 1.52; 95% CI, 1.07-2.16; P = .02) had greater efficacy than placebo for White participants. Only varenicline (OR, 2.63; 95% CI, 1.26-5.48; P = .01) had greater efficacy than placebo for Black participants. Baseline, postbaseline, and safety characteristics differed by race, but these variables did not eliminate the association of race with CAR. Black participants had 49% reduced odds of CAR for weeks 9 to 24 compared with White participants in the adjusted model (OR, 0.51; 95% CI, 0.39-0.66; P < .001). Conclusions and Relevance: Black and White smokers achieved the highest rate of abstinence while taking varenicline, suggesting that it is the best first-line therapy for these groups. However, Black smokers were less responsive to all therapies, including placebo. Understanding variables (eg, socioeconomic or biological) beyond those may lead to improved treatment outcomes for Black smokers. Trial Registration: ClinicalTrials.gov Identifier: NCT01456936.

High-dose and low-dose varenicline for smoking cessation in adolescents: a randomised, placebo-controlled trial.

BACKGROUND: Although cigarette smoking typically begins in adolescence, evidence for successful pharmacological smoking cessation interventions for this population is scarce. In adult smokers, varenicline is the most effective single pharmacotherapy. The aim of this study was to assess the efficacy and tolerability of varenicline for smoking cessation in adolescents. METHODS: We did a randomised, placebo-controlled trial with adolescent smokers aged 12-19 years who were seeking treatment to quit at 57 outpatient centres (in the USA, Russia, South Korea, Taiwan, Canada, and Georgia). Participants were randomly assigned (1:1:1) to receive 12 weeks of high-dose varenicline (1 mg twice daily; 0·5 mg twice daily if bodyweight ≤55 kg), low-dose varenicline (0·5 mg twice daily; 0·5 mg once daily if bodyweight ≤55 kg), or placebo, then followed up for 40 additional weeks. At all visits, participants received brief, developmentally tailored smoking cessation counselling (<10 min per session) delivered by a trained counsellor. The primary efficacy outcome was continuous abstinence from weeks 9 to 12, measured via a Nicotine Use Inventory and confirmed by urine cotinine testing. The primary tolerability outcome was frequency of treatment-emergent adverse events, including neuropsychiatric adverse events, occurring after the first dose and within 30 days of the last dose of study medication. This trial is registered with ClinicalTrials.gov, NCT01312909. FINDINGS: Between April 26, 2011, and Jan 18, 2018, 312 participants were enrolled and completed participation in the study: 109 in the high-dose varenicline group, 103 in the low-dose varenicline group, and 100 in the placebo group. The continuous abstinence rates from week 9 to 12 were 20% (22 of 109) in the high-dose varenicline group, 27% (28 of 103) in the low-dose varenicline group, and 18% (18 of 100) in the placebo group. Abstinence rates between high-dose varenicline and placebo groups (odds ratio [OR] 1·18 [95% CI 0·59-2·37]; p=0·63) and between low-dose varenicline and placebo groups (1·73 [0·88-3·39]; p=0·11) did not differ significantly. Treatment-emergent adverse events occurred in 65 (60%) of 108 participants in the high-dose group, 53 (53%) of 100 in the low-dose group, and 52 (53%) of 99 in the placebo group, and most were rated as mild. Neuropsychiatric treatment-emergent adverse events occurred in 18 (17%) of 108 participants in the high-dose group, 11 (11%) of 100 in the low-dose group, and 12 (12%) of 99 in the placebo group, and none was rated as severe. INTERPRETATION: This trial did not show an advantage in abstinence with varenicline compared with placebo among adolescent smokers. The rates of treatment-emergent adverse events were similar to those in previous trials of adult smokers, raising no new tolerability signals. These findings do not support the use of varenicline as a first-line pharmacotherapy for smoking cessation in adolescents. FUNDING: Pfizer.

Impact of smoking on cardiovascular events in patients with coronary disease receiving contemporary medical therapy (from the Treating to New Targets [TNT] and the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] trials).

To define the incremental risk of cigarette smoking in patients with coronary disease receiving contemporary medical therapy, we performed a post hoc analysis of 18,885 patients by combining data from the Treating to New Targets (TNT) and the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trials. These studies compared high-dose treatment (atorvastatin 80 mg/day) to moderate-dose treatment (atorvastatin 10 mg/day in TNT and simvastatin 20 to 40 mg/day in IDEAL) in patients with established coronary heart disease. The primary end point of this pooled analysis was major cardiovascular events, a composite of cardiac death, myocardial infarction, stroke, or resuscitated cardiac arrest. At baseline 4,196 patients had never smoked, 11,513 were ex-smokers, and 3,176 were current smokers. The adjusted hazard ratio for current smokers compared to never smokers was 1.68 (95% confidence interval 1.46 to 1.94) and that for current smokers compared to ex-smokers was 1.57 (95% confidence interval 1.41 to 1.76). Event rates for current smokers compared to ex-smokers were similarly increased in each treatment group. The difference in absolute event rates between current and ex-smokers in this pooled analysis was 4.5%, which is >2 times as large as the decrease in absolute event rates between high-dose and moderate-dose statin therapy found in the IDEAL (1.7%) and TNT (2.2%) trials, respectively. In conclusion, in patients with coronary disease receiving modern medical therapy, smoking cessation is of substantial benefit with a number needed to treat of 22 to prevent a major cardiovascular event over 5 years. Smoking cessation deserves greater emphasis in secondary prevention.