April 14, 2009 — Two randomized controlled trials reported in the April 7 issue of the Annals of Internal Medicine examined cutting-edge strategies to improve the population impact of existing strategies for tobacco smoking cessation.
"Cigarette smoking is a chronic, relapsing illness that is inadequately addressed in primary care practice," write Edward F. Ellerbeck, MD, MPH, from University of Kansas Medical Center in Kansas City, and colleagues. "Although most smokers will not quit after a single intervention, few studies have addressed the chronic nature of nicotine dependence by providing systematic, repetitive treatment opportunities. Providing treatment only to smokers who are already prepared to quit further limits the reach of current smoking cessation interventions."
Smoking Cessation, Counseling, Pharmacotherapy: First Study
The goal of the first randomized controlled trial was to compare cessation rates achieved with pharmacotherapy alone or combined with either moderate-intensity or high-intensity disease management including counseling and provider feedback.
From June 2004 to December 2007, a total of 750 persons who smoked more than 10 cigarettes per day were recruited from 50 rural primary care practices and randomly assigned to receive pharmacotherapy alone (n = 250), pharmacotherapy plus up to 2 counseling calls (moderate-intensity disease management; n = 249), or pharmacotherapy plus up to 6 counseling calls (high-intensity disease management; n = 251). These interventions were offered every 6 months for 2 years, and all participants were offered free pharmacotherapy. After counseling, patients in the moderate-intensity and high-intensity disease management groups had progress reports faxed to their clinicians.
The primary outcome measure was self-reported, point-prevalence smoking abstinence at 24 months. Secondary outcomes were overall (0 - 24 months) analyses of smoking abstinence, use of pharmacotherapy, and discussions about smoking with clinicians. Outcome measurements were performed by research assistants blinded to treatment assignment.
All treatment groups had similar use of pharmacotherapy. During the first, second, third, and fourth 6-month treatment cycles, 473 (63.8%) of 741 participants, 302 (40.9%) of 739 participants, 175 (23.9%) of 732 participants, and 179 (24.7%) of 726 participants requested pharmacotherapy, respectively. Treatment groups also did not differ in the percentage of participants who discussed smoking cessation with their clinician (37.5% - 59.5% of those who reported that they had seen a clinician during any given treatment cycle).
Throughout the study, abstinence rates improved. In overall analyses, abstinence rates were higher in the high-intensity disease management group vs the moderate-intensity disease management group (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.00 - 2.03) and in the combined disease management groups vs the pharmacotherapy-alone group (OR, 1.47; 95% CI, 1.08 - 2.00).
In the high-intensity and moderate-intensity disease management groups, self-reported abstinence at 24 months was 68 (27.9%) of 244 participants and 56 (23.5%) of 238 participants, respectively (OR, 1.33; 95% CI, 0.88 - 2.02) vs 56 (23.0%) of 244 participants in the pharmacotherapy-alone group. For combined disease management vs pharmacotherapy alone, OR was 1.12 (95% CI, 0.78 - 1.61).
"Smokers are willing to make repeated pharmacotherapy-assisted quit attempts, leading to progressively greater smoking abstinence," the study authors write. "Although point-prevalence abstinence did not differ at 24 months, analyses that incorporated assessments across the full 24 months of treatment suggest that higher-intensity disease management is associated with increased abstinence."
Limitations of this study include inability to separate the effect of pharmacotherapy management from the provision of free pharmacotherapy and validation of cessation in only 58% of self-reported quitters.
Triple-Combination Pharmacotherapy: Second Study
The second randomized trial evaluated triple-combination pharmacotherapy for medically ill smokers.
"Smokers with medical illnesses are at particular risk for complications caused by tobacco," write Michael B. Steinberg, MD, MPH, from University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School and School of Public Health, and Rutgers University in New Brunswick, and colleagues. "Clinical trial data on the effectiveness of triple-combination pharmacotherapy for tobacco dependence treatment in these high-risk smokers are not available."
The purpose of this trial was to compare extended duration of a triple-medication combination vs standard-duration therapy with the nicotine patch alone and to determine 6-month abstinence rates in smokers with medical illnesses.
From 2005 to 2007, a total of 127 smokers 18 years or older with prespecified medical illnesses were recruited from the local community and evaluated at a single primary care setting. Blocked randomization was used to assign participants to receive either the nicotine patch alone for a standard 10-week, tapering course (n = 64) or the combination of nicotine patch, nicotine oral inhaler, and bupropion as needed (n = 63). Using computer-generated tables, nonstudy staff randomly assigned participants by telephone. To maintain concealment, no study staff had access to the randomization tables before randomization. However, participants and study personnel were not blinded to treatment assignment.
The main endpoint of the study was abstinence at 26 weeks after target quit date, confirmed by 7-day, exhaled carbon monoxide, and secondary endpoints were the time to first relapse, duration of medication use, and adverse effects of medications. Analyses were by intent-to-treat. Participants who were lost to follow-up (13 receiving patch alone and 18 receiving combination therapy) were classified as still smoking.
Baseline characteristics were similar in both treatment groups. In the combination group, abstinence rate at 26 weeks was 35% (22/63 patients) vs 19% (12/64 patients) in the patch-alone group (relapse benefit, 16%; 95% CI, 1% - 31%; P = .04). In the combination group, the adjusted OR for abstinence was 2.57 (95% CI, 1.05 - 6.32; P = .041), and the median time to relapse was significantly longer vs the patch-alone group (65 days vs 23 days; P = .005).
Some adverse effects were reported more frequently in the combination group vs the patch-alone group, including insomnia (25% vs 9%) and anxiety (22% vs 3%). However, both groups had similar study discontinuation rate because of adverse events (6%).
"Flexibly dosed triple-combination pharmacotherapy for up to 6 months was more effective than standard-duration nicotine patch therapy for outpatient smokers with medical illnesses," the study authors write.
Limitations of this study include loss to follow-up in approximately one quarter of participants, with similar proportions between treatment groups; and lack of blinding of treatment personnel and participants.
The Clinician’s Role
In an accompanying editorial, Nancy A. Rigotti, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, warns that care for tobacco dependence must not be fragmented and must still be coordinated by the clinician.
"Currently, the focus is on devising systems to institutionalize the routine identification and treatment of smokers in a way that allows busy clinicians to delegate some of the work of carrying out the recommendations of the USPHS [US Public Health Service] clinical practice guideline to others," Dr. Rigotti writes. "The physician's role in this model is to advise cessation, discuss pharmacotherapy options, and refer the smoker for counseling support."
"Steinberg and coworkers indicate that the discussion of pharmacotherapy should become more sophisticated," Dr. Rigotti concludes. "Ellerbeck and colleagues propose adding a population-based outreach strategy to office-based systems to improve treatment reach. A 'direct-to-smoker' outreach strategy might appeal to physicians because it reduces the burden of managing tobacco smoking, a major public health hazard."
The National Cancer Institute supported Dr. Ellerbeck's study, and study medication was provided by GlaxoSmithKline. The authors in Dr. Ellerbeck's study have disclosed no relevant financial relationships. The Cancer Institute of New Jersey and the Robert Wood Johnson Foundation supported Dr. Steinberg's study. Some of the coauthors of Dr. Steinberg's study have disclosed various financial relationships with the New Jersey Department of Health and Senior Services, National Institute of Drug Abuse; Pfizer; GlaxoSmithKline; and/or National Institutes of Health.
Dr. Rigotti has disclosed various financial relationships with Pfizer, sanofi-aventis, and Nabi Biopharmaceuticals.
Ann Intern Med. 2009;150:437-446, 447-454, 496-497.
Clinical Context
Although clinicians see approximately 70% of smokers annually, only half of smokers discuss their tobacco use with their clinician. Even fewer smokers receive counseling or treatment to stop smoking. This is despite evidence that advice regarding smoking cessation can be effective. In addition to counseling, clinicians may prescribe drug therapy proven to improve the rate of abstinence from smoking.
Two new studies examine the use of pharmacotherapy, with or without enhanced counseling, to promote cessation among cohorts of smokers.
Study Highlights
Ellerbeck and colleagues
This study was conducted in 50 rural primary care practices in Kansas. Patients eligible for study participation were adults older than 18 years who smoked more than 10 cigarettes per day for at least 1 year.
All participants were offered free pharmacotherapy with a 6-week course of nicotine patches or a 7-week course of sustained-release bupropion 150 mg twice daily.
Study subjects were randomly assigned to receive pharmacotherapy alone, pharmacotherapy plus moderate-intensity disease management, or pharmacotherapy plus high-intensity disease management. Moderate-intensity disease management included up to 2 counseling phone calls every 6 months, whereas high-intensity management allowed up to 6 calls every 6 months.
The primary outcome was self-reported 7-day smoking abstinence at 24 months. A minority of patients completed salivary cotinine assays to determine the validity of self-reports.
750 participants underwent randomization. The average number of cigarettes smoked daily at baseline was 24, and most patients were at the contemplation stage of smoking cessation.
The use of pharmacotherapy was similar among randomly assigned groups and waned with time. The average numbers of counseling calls in the moderate-intensity and high-intensity management groups were 8.2 and 3.6, respectively.
The rates of self-reported abstinence at 24 months were 23%, 23.5%, and 27.9% in the pharmacotherapy-alone, moderate-intensity management, and high-intensity management groups, respectively. There was no significant difference among groups in this outcome.
However, interim analyses of abstinence rates between 0 and 24 months demonstrated that the high-intensity management group was superior to the moderate-intensity group (OR of abstinence, 1.43), and both disease management groups were superior to the pharmacotherapy-alone group (OR, 1.47).
A cost-analysis demonstrated that higher-intensity disease management was more expensive vs the other treatment groups.
Steinberg and colleagues
Study participants smoked at least 10 cigarettes per day and also had concomitant chronic illness.
Participants were randomly assigned to a standard tapering course of the nicotine patch for 10 weeks or to a triple-drug regimen. The triple-drug regimen consisted of nicotine patches, a nicotine inhaler, and sustained-release bupropion at 150 mg/day. Study subjects receiving triple-drug therapy were advised to taper the use of the nicotine patch and bupropion as symptoms allowed, and they could use the nicotine inhaler as needed throughout the study period of 26 weeks.
The primary outcome was point abstinence from smoking at 26 weeks after target quit date. Abstinence was confirmed with measurements of exhaled carbon monoxide.
127 patients underwent randomization. Two thirds of participants smoked at least 20 cigarettes daily.
Participants receiving the patch alone used this treatment for an average of 35 days, whereas the triple-drug group used study treatment for a mean duration of 89 days. In the triple-drug group, the nicotine inhaler was the most commonly used drug at 26 weeks.
The triple-drug group had significantly higher rates of abstinence from smoking at 26 weeks vs the nicotine patch group (35% vs 19%, respectively; adjusted OR, 2.57). The difference between groups appeared by week 4.
Triple-drug therapy was also associated with a longer time to relapse (65 vs 23 days, respectively).
Rates of treatment discontinuation because of adverse events were similar in both treatment groups. Insomnia, anxiety, fatigue, and diarrhea were more common in participants receiving triple-drug therapy vs the nicotine patch alone.
Pearls for Practice
The first current study by Ellerbeck and colleagues demonstrates that counseling via telephone improved overall rates of self-reported abstinence from smoking during a 24-month study period, but the final rates of smoking abstinence at 24 months were similar in comparing interventions of counseling plus pharmacotherapy vs pharmacotherapy alone.
The second current study by Steinberg and colleagues demonstrates that flexibly-dosed triple-drug therapy promoted better rates of abstinence from smoking and a longer duration to relapse vs nicotine patch therapy alone.
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Two Studies Examine How to Improve Smoking Cessation Strateg
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