Quit rates after failed treatment for smoking cessation improve by upping dosage

For smokers who were not able to quit following initial treatment with varenicline or combined nicotine replacement therapy (CNRT), bumping up their dosages or switching from CNRT to varenicline appears to be an effective rescue strategy, as shown in a study.

In the group of participants who were treated with varenicline for 6 weeks but did not achieve abstinence, the abstinence rate at week 12 was 20 percent among those who subsequently received increased varenicline dosage, 0 percent among those who switched to CNRT, and 3 percent among those who continued treatment with their initial varenicline dosage. Evidence indicated a very high likelihood (more than 99 percent posterior probability) that continuing varenicline at the initial dosage would yield worse outcomes than switching to a higher dosage. [JAMA 2024;doi:10.1001/jama.2024.4183]

Meanwhile, the abstinence rate at week 12 in the group of participants who were treated with CNRT for 6 weeks but did not achieve abstinence was higher among those who subsequently received increased CNRT dosage (14 percent) and those who switched to varenicline (14 percent) than among those who continued with their initial CNRT dosage (8 percent). A strategy of either increasing the CNRT dosage or switching to varenicline had a more than 99 percent posterior possibility of being more effective than maintaining the initial CNRT dosage.

Raising the dosage of either medication did not compromise safety, according to the investigators, noting that the participants who received increased dosage of varenicline or CNRT had no increased risk of adverse events compared with those who continued with the initial treatment dosage.

For the secondary outcome of continuous abstinence (30 days) at 6 months, the results “indicated that only increased dosages of the CNRT and varenicline provided benefit over continuation of the initial treatment dosages,” the investigators said. “[In addition,] early quitters (week-6 abstainers) may benefit equally over the long term from their initial medication.”

Smoking cessation reduces the prevalence of tobacco-related cancers, stroke, cardiovascular disease, and diabetes, among others, and their associated morbidity and mortality. Not only does quitting reduce the associated healthcare expenditures but, more importantly, paves the way for better health outcomes, the investigators pointed out.

National surveys indicate a strong desire to quit smoking, with nearly 70 percent of smokers attempting to quit each year. However, the journey to becoming smoke-free can be challenging, such that only about 7.5 percent succeed and most require multiple quit attempts (≈ 6) to achieve long-term success. [MMWR Morb Mortal Wkly Rep 2017;65:1457-1464; MMWR Morb Mortal Wkly Rep 2019;68:1013-1019; BMJ Open 2016;6:e011045]

With the present study, clinicians may be able to guide their patients towards successful smoking cessation, helping them live healthier lives free from the burden of tobacco-related illnesses, according to the investigators.

The study included 490 participants (mean age 48.1 years, 43 percent female, 58 percent non-Hispanic White) who smoked an average of 20 cigarettes per day. They were randomly assigned to receive initial treatment with either 2 mg/d of varenicline or CNRT of a 21-mg patch plus 2-mg lozenge. Weekly brief counselling was conducted.

At week 6, abstinence was achieved by 63 of 88 participants who received varenicline and 42 of 54 of those who received CNRT. These participants maintained their treatment dosage through week 12.