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Am Fam Physician. 2020;102(1):17-18

Author disclosure: No relevant financial affiliations.

Clinical Question

Does combining long-acting and short-acting nicotine replacement therapy (NRT) help patients quit smoking? Is any single form of NRT more effective than another?

Evidence-Based Answer

Patients using a combination of nicotine patch and fast-acting NRT are more likely to quit smoking than those on any single therapy alone (number needed to treat [NNT] = 29; 95% CI, 20 to 47). Rates of smoking cessation are not significantly different when directly comparing nicotine patches with fast-acting forms (e.g., lozenges, gum, inhalers, sprays), although dropout rates are higher with fast-acting forms. Rates of smoking cessation do not significantly differ among the various fast-acting forms.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

In 2017, roughly 47.4 million U.S. adults (19.3%) used tobacco products; cigarettes were the most commonly used product.2 Tobacco use is a leading cause of preventable illness and death worldwide, accounting for more than 7 million deaths annually.1 Although two-thirds of smokers are interested in quitting, less than one-third use evidence-based cessation aids, and less than 10% successfully quit annually.3 The authors of this review sought to determine the effectiveness and safety of different formulations, doses, durations, and schedules of NRT.

This review included 63 randomized controlled trials, involving 41,509 participants, that compared various forms of NRT with a primary outcome of smoking cessation at six months (with or without additional 12-month follow-up) and a secondary outcome of cardiac adverse effects.1 Participants were 45 years of age on average and smoked at least one pack per day.

High-quality evidence gathered from 14 randomized controlled trials with 11,356 participants suggested that a combination of nicotine patches and fast-acting NRT (e.g., lozenges, gum, inhaler, oral spray) yielded better smoking cessation rates than either single therapy alone (absolute risk reduction [ARR] = 3.5%; 95% CI, 2.1% to 5%; NNT = 29; 95% CI, 20 to 47) with no statistically significant difference in adverse effects. The duration of combination therapy did not appear to impact quit rates. One study of 402 participants comparing 50-week gum use and 10-week gum use found no difference in smoking cessation rates (ARR = 1.7%; relative risk [RR] = 1.04; 95% CI, 0.82 to 1.32). Three studies, with a combined 2,168 subjects, compared treatment durations of patch plus gum at intervals between two and 26 weeks, and found no difference in cessation rates.

Quit rates for 21-mg patches alone were higher than for 14-mg patches alone (NNT = 12), but increasing doses up to 44 mg had no added benefit. Dropout rates were lower with the patch (five per 1,000) compared with fast-acting forms (23 per 1,000; number needed to harm = 56; 95% CI, 17 to 222; RR = 4.23; 95% CI, 1.54 to 11.63; three studies; 1,482 participants). None of the eight studies (3,319 participants) that compared a form of fast-acting NRT with nicotine patches found a statistically significant difference in rates of smoking cessation (RR = 0.90; 95% CI, 0.77 to 1.05). The 4-mg gum alone resulted in greater smoking cessation rates than the 2-mg gum alone (RR = 1.85; 95% CI, 1.36 to 2.50) in high-dependency smokers, but there was no difference in low-dependency smokers, as defined by established dependency scales.

The cost, dosing schedule, and whether the formulation was chosen by the patient or the physician did not affect cessation rates. Other smoking cessation aids, such as bupropion (Wellbutrin) and varenicline (Chantix), were not examined in this review.

The U.S. Preventive Services Task Force (USPSTF) recommends using a combination of behavioral interventions and pharmacotherapy for all nonpregnant smokers who are trying to quit. According to the USPSTF, the best and most effective combinations are those that are acceptable to and feasible for the patient.4 This review demonstrates that there are multiple effective nicotine replacement interventions, allowing flexibility for patients to choose the method that will work best for them.

The practice recommendations in this activity are available at http://www.cochrane.org/CD013308.

Editor's Note: The numbers needed to treat and harm, confidence intervals, absolute risk reductions, and relative risks reported in this Cochrane for Clinicians were calculated by the authors based on raw data provided in the original Cochrane review.

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