Smokers who use two forms of nicotine replacement therapy (NRT), including a patch and nicotine gum, lozenges or other short-acting delivery treatments, are more likely to successfully quit smoking than those who rely on a single NRT, according to Cochrane reviewers. In a report examining the efficacy and safety of different forms, deliveries, and doses of NRT for smoking cessation, Nicola Lindson, PhD, of the University of Oxford in England, and colleagues, concluded that there is now "high quality evidence" supporting the use of dual therapy, based on their review of 63 trials involving around 41,500 participants. Using a nicotine patch and another form of NRT, such as a gum or lozenge, was associated with a 5% to 36% increase in the likelihood of successful smoking cessation versus using NRT alone. Use of the higher dose of widely available nicotine gum (containing 4 mg of nicotine instead of 2 mg) and beginning NRT before the smoking quit date were also associated with a higher likelihood of successful smoking cessation, they wrote in the Cochrane Review. Lindson told MedPage Today that earlier Cochrane reviews examining NRT, including one in 2018, also compared the treatment to placebo or no treatment at all. Those reviews confirmed the efficacy of NRT -- available as skin patches, gum, nasal and oral spray, inhalers, lozenges, and tablets -- in helping smokers kick the habit. "That is now a settled question," she said. "What we were really trying to do here is explore the best ways to use NRT to make it as effective as possible." In the analysis, 17% of smokers who combined a patch with another type of NRT successfully quit smoking versus 14% of smokers who used a single type of NRT. "That may sound like a small difference,"but it is important to remember than giving up smoking is hard," Lindson said. "So any increase in successful outcomes is important, especially on a population level." Review Details The review included all randomized trials with follow-up of ≥6 months; trials comparing NRT to control or to other non-NRT pharmacotherapies were not included. Quit attempts were considered successful when the participants had abstained from smoking for ≥6 months. In all, 24 of 63 studies included in the analysis were judged to have a high risk of bias, but restricting the analysis to studies with a low or unclear risk of bias did not significantly alter the findings. The analysis revealed there was high-certainty evidence that combination NRT (fast-acting form plus patch) results in higher long-term quit rates than single form NRT (risk ratio 1.25, 95% CI 1.15-1.36, I2=4%; 14 studies with 11,356 participants). Also, there was moderate-certainty evidence indicating that 42/44 mg are as effective as 21/22 mg (24-hour) patches (RR 1.09, 95% CI 0.93-1.29, I2=38%; five studies with 1655 participants), and that 21 mg are more effective than 14 mg (24-hour) patches (RR 1.48, 95% CI 1.06-2.08; one study with 537 participants). Results of five studies comparing 4 mg gum to 2 mg gum found the higher dose to be more effective (RR 1.43, 95% CI 1.12-1.83, I2=63%; 856 participants), but subgroup analysis suggested that only smokers who are highly dependent may benefit. Nine studies examining the effect of starting NRT prior to quit day (pre-loading) -- versus using it from quit day onward -- exhibited moderate-certainty evidence, limited by risk of bias, of a favorable effect of pre-loading on abstinence (RR 1.25, 95% CI 1.08-1.44, I2=0%; nine studies with 4,395 participants). There was high-certainty evidence suggesting that using either a form of fast-acting NRT or a nicotine patch results in similar long-term quit rates (RR 0.90, 95% CI 0.77-1.05, I2 =0%; eight studies with 3,319 participants). There was no evidence of an increased safety risk in people using two forms of NRT, or higher doses of fast-acting NRT, although the researchers did note that most of the studies did not examine safety. "We also looked at how long NRT should be used for, whether NRT should be used on a schedule or as wanted, and whether more people stop smoking when NRT is provided for free versus if they have to pay for it. However, more research is needed to answer these questions," the researchers wrote. Lindson said many guidelines now recommend dual NRT to smokers who want to quit, and most smoking cessation specialists prescribe it. But she added that general practitioners and the public largely have not gotten the message that attempting smoking cessation with two forms of NRT can improve cessation success. Not as Good as Vaping? Smoking cessation researcher K. Michael Cummings, of the Medical University of South Carolina at Charleston, agreed that the Cochrane findings will come as no surprise to people in the field. "Dual NRT treatment is common practice within the treatment community, but that doesn't mean other clinicians and the public are aware of the benefits," he told MedPage Today. Cummings, who was not involved in the review, added that the evidence favoring higher doses of NRT, and starting therapy before a quit date, is also strong. But he said even the best available, approved NRT therapies may prove to be less effective for smoking cessation than vaping, due to a key difference in delivery. While patches, gum, and other approved NRTs deliver nicotine slowly, vaping products more closely mimic nicotine delivery from cigarette smoking. This is especially true for popular, high nicotine e-cigarettes like the JUUL brand. Cummings cited a 2019 randomized trial of e-cigarettes versus NRT that found vaping to be almost twice as effective as NRT for smoking cessation. But the study also revealed that 80% of participants randomized to vaping who quit smoking cigarettes were still vaping a year later (63 of 78 participants), while just 9% of those who successfully stopped smoking with NRT were still the therapy a year later (four of 44 participants). Source
