Hatsukami DK, et al. - This analysis focused on the impacts of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure. Researchers found that immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time vs gradual reduction or a control group among smokers. They did not observe significant differences between gradual reduction and control.

Methods

• Researchers conducted a double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention at 10 US sites.
• Between July 2014 and September 2016, a volunteer sample of daily smokers with no intention to quit within 30 days was enlisted, with the last follow-up completed in March 2017.
• Main interventions were
  • Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes;
  • gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes;
  • maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes.
• Main outcomes and measures analyzed were between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention.

Results

• Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were noted in the immediate compared with gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055).
• Significantly lower levels of exposure were noted in the immediate reduction compared to control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055).
• They did not find significant differences between the gradual reduction compared to control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P=.18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P=.64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P=.52).