ABSTRACT
INTRODUCTION: Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed. METHODS: This partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8-12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy. RESULTS: Abstinence rates were 42.9% (95% CI: 36-64) in the control group versus 30.4% (95% CI: 23-37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67-80) versus 52% (95% CI: 49-64) at Week 12 (p<0.001), respectively. The strategy of combining drugs after Week 4 increased abstinence rates in both groups and the significant difference between genetic and control groups was maintained. CONCLUSIONS: Results show that using these selected genetic markers was inferior to starting treatment with varenicline (control group), which is currently the most effective smoking cessation drug; moreover, the addition of bupropion in cases of varenicline monotherapy failure improves the efficacy rate until the end of treatment. CLINICAL TRIAL IDENTIFIER: NCT03362099.
ABSTRACT
BACKGROUND: To establish the impact of tobacco smoking on mortality is essential to define and monitor public health interventions in developing countries. METHODS: The Smoking-Attributable Mortality, Morbidity and Economic Costs (SAMMEC) software was used to estimate the smoking attributable mortality (SAM) in 15 Brazilian State Capitals and the Federal District for the year 2003. Smoking prevalence and mortality data of people aged 35 years or older were obtained for each city from the Brazilian Household Survey on Non Communicable Diseases Risk Factors (2002-2003) and from the Brazilian Mortality System (2003), respectively. RESULTS: In 2003, of the 177,543 deaths of persons aged 35 years and older 24,222 (13.64%) were attributable to cigarette smoking. This total represents 18.08% of all male deaths (n = 16,896) and 8.71% (n = 7,326) of all female deaths in these cities. The four leading causes of smoking-attributable death were chronic airways obstruction (4,419 deaths), ischemic heart disease (4,417 deaths), lung cancer (3,682 deaths), and cerebrovascular disease (3,202 deaths). Cigarette smoking accounted for 419,935 years of potential life lost (YPLL) (279,990 YPLL for men and 139,945 YPLL for women) in the same period. CONCLUSION: Tobacco use caused one out of five male deaths and one out of ten female deaths in the sixteen cities in 2003. Four leading causes of smoking attributable deaths (ischemic heart disease, chronic airways obstruction, lung cancer and cerebrovascular disease) accounted for 64.9% of SAM. Effective and comprehensive actions must be taken in order to slow this epidemic in Brazil.
