REVIEW OF: Cinciripini PM et al, JAMA 2024;331:1722–1731

STUDY TYPE: RCT

Smoking cessation is tough—most smokers don’t quit on the first try. In this trial, the researchers aimed to find the best follow-up strategy for patients who didn’t quit after an initial attempt, using varenicline or combined nicotine replacement therapy (CNRT).

The study used a two-phase randomized approach. In phase 1, 490 participants—who smoked about 20 cigarettes a day—received either varenicline (2 mg/day) or CNRT (a 21 mg nicotine patch plus 2 mg lozenges taken as needed, with a recommended use of at least 6 lozenges per day). Those who didn’t quit after 6 weeks were re-randomized in phase 2. Phase 2 had three options: continue the same treatment; increase the dose (to either 3 mg varenicline or 2 patches of CNRT); or switch treatments.

Phase 1 results: After 6 weeks, 36% of the varenicline group quit smoking, compared to 22% in the CNRT group.

Phase 2 results: For those who didn’t quit on CNRT, increasing the CNRT dose or switching to varenicline each led to a 14% quit rate, compared to only 8% for those who continued at the same dose. For non-quitters on varenicline, increasing the dose to 3 mg/day improved the quit rate to 20%. However, continuing the same dose resulted in only a 3% quit rate, and switching to CNRT led to no success (0% quit rate).

CARLAT TAKE
Consider CNRT a failure if patients aren’t abstinent at week 6, and then either increase the dose or try varenicline if appropriate. Although varenicline 3 mg/day is above the licensed dose, it may be worth trying if patients are tolerating 2 mg but not abstinent. Varenicline does come with the potential for suicidality, depression, agitation, or psychosis, but the FDA downgraded its black box warning in 2016 (see “How to Use Varenicline (Chantix)” in the May 2022 issue of TCPR).