BACKGROUND AND PURPOSE:

• Cinciripini et al. (JAMA Netw Open, 2024) determine the best subsequent strategy for nonabstinence following initial treatment with varenicline or combined nicotine replacement therapy (CNRT)

METHODS:

• Double-blind, placebo-controlled, sequential multiple assignment randomized trial
• Participants
  • 18 to 75 years
  • Smoked 5 or more cigarettes per day with an expired CO of ≥6 ppm
• Interventions
  • Initial randomization
    • Varenicline for 6 weeks, 2 mg/d
    • CNRT for 6 weeks, 21 mg patch + 2 mg lozenge
  • Rerandomization for those who were nonabstainers after 6 weeks
    • Continue for 6 weeks
    • Switch to other treatment option for 6 weeks
    • Increase medication dose for 6 weeks
      • ≥3mg/d varenicline | 42 mg patch + lozenges
• Study design
  • All participants received brief weekly counseling
• Primary outcomes
  • Biochemically verified 7-day point prevalence abstinence at the end of treatment at 12 weeks

RESULTS:

• 490 participants
  • Female: 43% | Non-Hispanic White: 58%
  • Mean age: 48.1 years
• After first phase
  • CNRT group
    • Abstinent: 54 participants | Nonabstinent: 191
    • Rerandomized: 151
  • Varenicline:
    • Abstinent: 88 | Nonabstinent: 157
    • Rerandomized: 122
• The end-of-treatment abstinence rate for phase 1 nonabstainers
  • Initial CNRT
    • Continued: 8% (95% credible interval [CrI], 6 to 10)
    • Increased dosage: 14% (95% CrI, 10 to 18)
    • Switched to varenicline: 14% (95% CrI, 10 to 18)
    • Absolute risk difference 6% (95% CrI, 6 to 11)
    • >99% posterior probability that either strategy conferred benefit over continuing the initial dosage
  • Initial varenicline
    • Continued: 3% (95% CrI, 1% to 4%)
    • Increased dosage: 20% (95% CrI, 16 to 26)
    • Switched to CNRT: 0% (95% CrI, 0 to 0)
    • Absolute risk difference 18% (95% CrI, 13% to 24%)
    • >99% posterior probability of increasing the varenicline dosage conferring benefit
• At 6 months, only increased dosages of the CNRT and varenicline provided benefit over continuation of the initial treatment dosages

CONCLUSION:

• For those who attempted to quit smoking using varenicline but did not achieve abstinence after the first attempt, increasing the dosage was more helpful than continuing at the initial dosage
• For those who used CNRT to quit, both increasing the CNRT dosage, or switching to varenicline, were more helpful than continuing at the same dosage
• The authors state

For individuals who do not achieve abstinence after treatment with varenicline, increasing the dosage enhances abstinence relative to continuing at the initial dosage, whereas for those who don’t achieve abstinence with CNRT, a dosage increase or switching to varenicline are viable rescue strategies, with continuous abstinence results favoring a dosage increase

Learn More – Primary Sources:

Smoking Cessation After Initial Treatment Failure With Varenicline or Nicotine Replacement: A Randomized Clinical Trial