Gradual Versus Abrupt Smoking Cessation

Context Patients may vary in their expressed preferences about how to stop smoking cigarettes. Whether an initial gradual reduction in cigarette use before an attempt at quitting is as effective as abrupt cessation is not known. Contribution In this trial, adult smokers randomly assigned to gradually reduce smoking before a planned quit date were less likely to achieve abstinence than those who quit abruptly. Implication Abrupt cessation of smoking is more likely to lead to sustained abstinence. Conventionally, smokers are advised to quit abruptly by setting a quit day to stop smoking in 1 step. Worldwide guidelines for smoking cessation generally recommend abrupt cessation and do not support a gradual reduction in smoking (13); however, many smokers report stopping gradually (46). It is important to know whether gradual cessation has a lower success rate so physicians can provide evidence-based advice. Evidence on whether gradual cessation is less effective than abrupt cessation conflicts. Observational data on quit attempts made primarily without behavioral support suggest that stopping abruptly is superior (4, 7). However, a Cochrane review of 10 randomized trials (8) suggests that the difference in quit rates achieved using the 2 approaches is slight, with a relative risk (RR) of 0.94 (95% CI, 0.79 to 1.13). Several trials included in the review had design features that make it difficult to discern whether the differences in quit rates were solely due to the method used to achieve abstinence. None were designed to assess noninferiority, and the pooled 95% CI obtained encompasses a substantial reduction in the efficacy of gradual compared with abrupt quitting. We conducted a large trial to test whether an initial gradual reduction in smoking results in noninferior quit rates compared with abrupt cessation. Methods Design We randomly assigned adult smokers to gradually reduce tobacco use over 2 weeks before a planned quit day (gradual-cessation group) or to stop smoking abruptly on a planned quit day (abrupt-cessation group). The gradual-cessation group received short-acting nicotine replacement therapy (NRT) and nicotine patches before the quit day. The abrupt-cessation group received only nicotine patches before the quit day. Both groups had behavioral counseling, nicotine patches, and short-acting NRT after the quit day. Our primary outcome was validated abstinence 4 weeks after the quit day. We also evaluated 6-month abstinence and whether outcomes differed according to participants' preferred method of quitting. Participants We recruited adult smokers who were addicted to tobacco, defined as those who smoked at least 15 cigarettes or 12.5 grams of loose-leaf tobacco daily or who had an end-expiratory carbon monoxide (CO) concentration of at least 15 ppm. Participants had to be willing to quit smoking 2 weeks after trial enrollment. Exclusion criteria included current participation in cessation treatment, contraindications to NRT, participation in other medical trials, and circumstances precluding the ability to meet the demands of the trial. Persons who were dependent on alcohol or illicit drugs or who had severe acute or chronic medical or psychiatric conditions were included unless their conditions were so severe that it was unlikely that they would be able to meet the demands of the trial. The lead general practitioner at 31 volunteer practices in England searched their electronic patient records and wrote to all registered patients who smoked to invite them to the study. Potential participants were encouraged to call the researchers who explained the trial and screened patients for eligibility. Eligible smokers were booked for an appointment with a research nurse during which the study was explained, eligibility was confirmed, and written informed consent was obtained. Interventions Participants were asked to set a quit day 2 weeks after enrollment, and the intervention differed between groups only during these weeks. In the gradual-cessation group, participants aimed to reduce smoking to half of the baseline amount by the end of the first week (known as visit 1) and to a quarter of the baseline amount at the end of the second week (visit 0) in daily increments. Reduction over 2 weeks was chosen because qualitative evidence suggests that this keeps persons more focused on quitting than longer reduction (9), data from a trial support this approach (10), and the 2-week reduction before quit day is current practice in the United Kingdom. (11). Participants in the gradual-cessation group chose 1 of the following 3 structured reduction programs: scheduled (1, 12), hierarchical, or smoke-free periods (Appendix). The nurse created reduction schedules with the participants to boost understanding and memory and discussed strategies to prompt adherence. Smoking reduction is more successful when participants use NRT (13), so we provided the gradual-cessation group with nicotine patches, 21 mg/d, and a choice of short-acting NRT products (gum, lozenges, nasal spray, sublingual tablets, inhalator, or mouth spray) during the reduction period. For such products as gum and lozenges, the instruction was to use 1 dose per cigarette missed. Participants in the abrupt-cessation group were asked to smoke as normal and not reduce between the baseline appointment and quit date. To balance the behavioral support time, participants identified the times of day when cigarettes would be the hardest to give up and planned strategies to avoid relapse after the quit day. Before quitting, participants in the abrupt-cessation group were asked to use nicotine patches, 21 mg/d, but no short-acting NRT. Nicotine patches were used in this group before the quit day because some evidence suggests that precessation NRT increases quit rates, and this protocol aimed to balance the effect between groups (14). Other than these differences, the treatment program in both groups was identical. Participants were seen by a research nurse at their primary care practice weekly for 2 weeks before their quit day (baseline and visit 1), the day before their quit day (visit 0), weekly for 4 weeks after quitting (visits 1 through 4), and finally 8 weeks after the quit day (visit 8). The behavioral support for both groups from visit 0 onward was withdrawal-oriented therapy, which is typical of a smoking cessation clinic in the United Kingdom (12, 15). Withdrawal-oriented therapy focuses on the commitment to abstain completely and provides support early, which is when withdrawal symptoms are worst and relapse is most likely. Pharmacotherapy was identical in both groups from the quit day onward and consisted of a nicotine patch, 21 mg/d, plus short-acting NRT of the participant's choice. Participants were encouraged to use their NRT liberally in anticipation of or in response to cravings. Randomization Participants were randomly assigned in a 1:1 ratio to gradual or abrupt cessation at the baseline visit. An independent statistician used Stata, version 10.1 (StataCorp), to accomplish randomization stratified by research nurse, with randomly ordered blocks of 2, 4, and 6 to ensure balance. After the participant granted consent, the research nurse opened sealed, numbered envelopes in turn. For pairs (for example, husband and wife), one person was allocated randomly and the other was allocated to the same group. Measures Participant demographic characteristics, smoking history, nicotine dependence, and preference for gradual or abrupt cessation were recorded at baseline. At each subsequent clinic session, we assessed the amount smoked and measured salivary cotinine and exhaled CO concentrations. Tobacco withdrawal symptoms were also measured using the mood and physical symptoms scale, which we present here as the mean scores for urge intensity and withdrawal symptoms (16). We also assessed adverse events, and participants rated the severity of possible symptoms of nicotine overdose during the 2-week (prequit day) period of NRT and concurrent smoking. Nicotine overdose symptoms were provided as a checklist, and participants were asked, "Have you been troubled by any of the following problems in the past 24 hours? " They rated each symptom on a scale ranging from "not at all" to "extremely. " All participants were asked to complete daily diaries in the 2 weeks before quit day to measure adherence to medication and behavioral instructions. Trial group preference was reassessed at 4-week follow-up. The primary outcome was Russell Standard 4-week abstinence. The Russell Standard allows a 2-week grace period from quit day for slips and uses an intention-to-treat approach that assumes that persons lost to follow-up are smokers. Russell Standard abstinence is validated by an exhaled CO concentration of less than 10 ppm (17). Secondary outcomes were Russell Standard abstinence at 8-week and 6-month follow-up; 7-day point prevalence abstinence at 4-week, 8-week, and 6-month follow-up, validated by an exhaled CO concentration of less than 10 ppm; and urges to smoke and nicotine withdrawal symptoms at 1- and 4-week follow-up. Statistical Analysis Our chosen noninferiority margin was equal to an RR of 0.81 or a 19% reduction in the effectiveness of quitting gradually compared with abruptly. This is an absolute difference in quit rates of 9.5 percentage points at 4 weeks, assuming a 50% quit rate in the abrupt-cessation group (18). Using a 1-sided of 5%, we needed 343 participants per group to have 80% power to detect this difference in the primary outcome. In the abstinence analysis, we present RRs because of the high incidence of abstinence (>10%). The primary noninferiority analysis (abstinence at 4 weeks) was based on a 1-sided of 0.05, and therefore a 90% CI was calculated. In accordance with CONSORT (Consolidated Standards of Reporting Trials) (17), we interpreted this CI in relation to our predetermined noninferiority margin (RR, 0.81). To assess superiority, which is