Dataset Information

Searching for Personalized Medicine for Binge Drinking Smokers: Smoking Cessation Using Varenicline, Nicotine Patch, or Combination Nicotine Replacement Therapy.

ABSTRACT:

Objective

Heavy drinking is common among smokers and is associated with especially poor health outcomes. Varenicline may affect mechanisms and clinical outcomes that are relevant for both smoking cessation and alcohol use. The current study examines whether varenicline, relative to nicotine replacement therapy, yields better smoking cessation outcomes among binge drinking smokers.

Method

Secondary data analyses of a comparative effectiveness randomized controlled trial of three smoking cessation pharmacotherapies (12 weeks of varenicline, nicotine patch, or nicotine patch and lozenge) paired with six counseling sessions were conducted. Adult daily cigarette smokers (N = 1,078, 52% female) reported patterns of alcohol use, cigarette craving, and alcohol-related cigarette craving at baseline and over 4 weeks after quitting. Smoking cessation outcome was 7-day biochemically confirmed point-prevalence abstinence.

Results

Binge drinkers had higher relapse rates than moderate drinkers at 4-week post-target quit day but not at the end of treatment or long-term follow up (12 and 26 weeks). Varenicline did not yield superior smoking cessation outcomes among binge drinkers, nor did it affect alcohol use early in the quit attempt. Varenicline did produce relatively large reductions in alcohol-related cigarette craving and overall cigarette craving during the first 4 weeks after quitting.

Conclusions

Varenicline did not yield higher smoking abstinence rates or reduce alcohol use among binge drinkers. Varenicline did reduce alcohol-related cigarette craving but this did not translate to meaningful differences in smoking abstinence. Varenicline's effects on smoking abstinence do not appear to vary significantly as a function of drinking status.

SUBMITTER: Kaye JT

PROVIDER: S-EPMC7437557 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Extended use of combined pharmacotherapies to treat tobacco dependence may increase smoking abstinence; few studies have examined their effectiveness. The objective of this study was to evaluate smoking abstinence with standard nicotine patch (NRT), extended use of combined formulations of nicotine replacement therapy (NRT+), or varenicline (VR).A total of 737 smokers, including those with medical and psychiatric comorbidities, were randomly assigned to one of the above three treatment conditions. The NRT group received 10 weeks of patches (21 mg daily maximum); the NRT+ group received patches (35 mg daily maximum) and gum or inhaler for up to 22 weeks; and the VR group received 1 mg twice daily for up to 24 weeks (22 weeks post target quit date). All participants also received six standardized 15-minute smoking cessation counseling sessions by nurses experienced in tobacco dependence treatment. The primary outcome was carbon monoxide-confirmed continuous abstinence rates (CAR) from weeks 5-52. Secondary outcomes were: CAR from weeks 5-10 and 5-22, and carbon monoxide-confirmed 7-day point prevalence (7PP) at weeks 10, 22, and 52. Adjusted and unadjusted logistic regression analyses were conducted using intention-to-treat procedures.The CARs for weeks 5-52 were 10.0 %, 12.4 %, and 15.3 % in the NRT, NRT+, and VR groups, respectively; no group differences were observed. Results with 7PP showed that VR was superior to NRT at week 52 (odds ratio (OR), 1.84; 97.5 % Confidence Interval (CI), 1.04-3.26) in the adjusted intention-to-treat analysis. Those in the VR group had higher CAR at weeks 5-22 (OR, 2.01; CI, 1.20-3.36) than those in the NRT group. Results with 7PP revealed that both NRT+ (OR, 1.72; CI, 1.04-2.85) and VR (OR, 1.96; CI, 1.20-3.23) were more effective than NRT at 22 weeks. As compared to NRT monotherapy, NRT+ and VR produced significant increases in CAR for weeks 5-10 (OR, 1.52; CI, 1.00-2.30 and OR, 1.58; CI, 1.04-2.39, respectively); results were similar, but somewhat stronger, when 7PP was used at 10 weeks (OR, 1.57; CI, 1.03-2.41 and OR, 1.79; CI, 1.17-2.73, respectively). All medications were well tolerated, but participants in the VR group experienced more fatigue, digestive symptoms (e.g., nausea, diarrhea), and sleep-related concerns (e.g., abnormal dreams, insomnia), but less dermatologic symptoms than those in the NRT or NRT+ groups. The frequency of serious adverse events did not differ between groups.Flexible and combination NRT and varenicline enhance success in the early phases of quitting. Varenicline improves abstinence in the medium term; however, there is no clear evidence that either varenicline or flexible, dual-form NRT increase quit rates in the long-term when compared to NRT monotherapy.ClinicalTrials.gov Identifier: NCT01623505 ; Retrospectively registered on July 13, 2011.

Project description:ImportanceSmoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality.ObjectiveTo compare the efficacies of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26-week quit rates.Design, setting, and participantsThree-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization.InterventionsParticipants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered.Main outcomes and measuresThe primary outcome was carbon monoxide-confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide-confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52.ResultsAmong 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, -0.76% (95% CI, -7.4% to 5.9%); for patch vs C-NRT, -4.0% (95% CI, -10.8% to 2.8%); and for varenicline vs C-NRT, -3.3% (95% CI, -9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did the nicotine patch for vivid dreams, insomnia, nausea, constipation, sleepiness, and indigestion.Conclusions and relevanceAmong adults motivated to quit smoking, 12 weeks of open-label treatment with nicotine patch, varenicline, or C-NRT produced no significant differences in biochemically confirmed rates of smoking abstinence at 26 weeks. The results raise questions about the relative effectiveness of intense smoking pharmacotherapies.Trial registrationclinicaltrials.gov Identifier: NCT01553084.

Project description:INTRODUCTION:Varenicline (VAR) is an effective smoking-cessation therapy compared to the commonly used nicotine-replacement therapy patch (NRT-P). However, comparative real-world evidence on smoking-cessation therapies is limited, especially for economic outcomes. METHODS:Using national claims databases (2012-2016) in the United States (US), adults initiating VAR or NRT-P without use of any other smoking-cessation products were followed for up to 1 year on a quarterly basis. Outcomes included smoking-attributable (SA) (cardiovascular, diabetes, pulmonary diseases, and smoking cessation) and all-cause costs (2017 US dollars). Adjusted mean costs were estimated from multivariable regressions, with baseline characteristics and propensity scores as covariates. Annual adjusted costs were calculated from quarterly averages. RESULTS:The VAR cohort (n = 209,284) was younger (mean age 46.7 vs. 49.0 years) and had fewer comorbidities [mean Charlson Comorbidity Index (CCI): 0.8 vs. 1.6] than the NRT-P cohort (n = 34,593). After adjustment, VAR cohort had lower SA and all-cause medical costs than NRT-P cohort in Quarters 1-4 (Q1-Q4) of follow-up, and had lower SA and all-cause total costs in Q2-Q4. Annually, VAR cohort had higher SA total costs ($307) and lower all-cause costs (- $2089) than NRT-P cohort. Annual medical costs were lower in VAR cohort (- $640 for SA and - $2876 for all-cause), and pharmacy costs were higher ($762 for SA and $777 for all-cause). In adherent patients (VAR: n = 38,744; NRT-P: n = 2702), VAR patients had lower annual medical costs (- $794 for SA and - $1636 for all-cause) and higher pharmacy costs ($1175 for SA and $1269 for all-cause); differences in SA and all-cause total costs were not statistically significant between treatment groups. CONCLUSIONS:Lower SA and all-cause medical costs associated with the use of VAR versus NRT-P resulted in savings in all-cause total costs and, among adherent patients, potentially offset the high pharmacy costs of VAR. FUNDING:Pfizer, Inc.

Project description:ImportanceQuitting smoking is enhanced by the use of pharmacotherapies, but concerns have been raised regarding the cardiovascular safety of such medications.ObjectiveTo compare the relative cardiovascular safety risk of smoking cessation treatments.Design, setting, and participantsA double-blind, randomized, triple-dummy, placebo- and active-controlled trial (Evaluating Adverse Events in a Global Smoking Cessation Study [EAGLES]) and its nontreatment extension trial was conducted at 140 multinational centers. Smokers, with or without established psychiatric diagnoses, who received at least 1 dose of study medication (n = 8058), as well as a subset of those who completed 12 weeks of treatment plus 12 weeks of follow up and agreed to be followed up for an additional 28 weeks (n = 4595), were included.InterventionsVarenicline, 1 mg twice daily; bupropion hydrochloride, 150 mg twice daily; and nicotine replacement therapy, 21-mg/d patch with tapering.Main outcomes and measuresThe primary end point was the time to development of a major adverse cardiovascular event (MACE: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) during treatment; secondary end points were the occurrence of MACE and other pertinent cardiovascular events (MACE+: MACE or new-onset or worsening peripheral vascular disease requiring intervention, coronary revascularization, or hospitalization for unstable angina).ResultsOf the 8058 participants, 3553 (44.1%) were male (mean [SD] age, 46.5 [12.3] years). The incidence of cardiovascular events during treatment and follow-up was low (<0.5% for MACE; <0.8% for MACE+) and did not differ significantly by treatment. No significant treatment differences were observed in time to cardiovascular events, blood pressure, or heart rate. There was no significant difference in time to onset of MACE for either varenicline or bupropion treatment vs placebo (varenicline: hazard ratio, 0.29; 95% CI, 0.05-1.68 and bupropion: hazard ratio, 0.50; 95% CI, 0.10-2.50).Conclusions and relevanceNo evidence that the use of smoking cessation pharmacotherapies increased the risk of serious cardiovascular adverse events during or after treatment was observed. The findings of EAGLES and its extension trial provide further evidence that smoking cessation medications do not increase the risk of serious cardiovascular events in the general population of smokers.Trial registrationclinicaltrials.gov Identifier: NCT01574703.

Project description:Introduction:The effectiveness of varenicline compared with nicotine replacement therapy (NRT) in achieving smoking cessation in older smokers has not been investigated. This study prospectively compared the effectiveness of varenicline relative to NRT in smokers aged 25-54 years and separately in smokers aged 55 years or older. Methods:Among 13 397 smokers participating in the Smoking Cessation Program in Taiwan, 2012-2015, 6336 (19.2%, aged ?55) received varenicline and 7061 received NRT patch or gum (23.2%, aged ?55). Participants self-reported smoking behaviors by phone interview after 6 months. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for 7-day, 1-month, and 6-month point-prevalence abstinence. Age-specific models adjusted for sex, education, marital status, smoke-years, nicotine dependence, medical institution, clinic visit number, and duration of medication received. Results:Among smokers aged 25-54 years, varenicline users had a greater point-prevalence abstinence than NRT users (e.g., 7-day point-prevalence: 34.0% vs. 23.5%), with adjusted OR ranging from 1.23 (CI: 1.09-1.39; 6-month point-prevalence) to 1.37 (CI: 1.24-1.50; 1-month point-prevalence). Among smokers aged 55 years or older, point-prevalence was similar for varenicline and NRT users (e.g., 7-day point-prevalence: 32.3% vs. 33.1%), and ORs did not suggest that varenicline has greater effectiveness than NRT. Sex and level of nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT. Conclusions:Varenicline did not offer greater effectiveness in achieving abstinence than NRT for smokers 55 years or older, whereas it was more effective than NRT in smokers aged 25-54 years. These findings highlighted the need for age-specific approaches for effective tobacco control. Implications:In this prospective investigation of a national cohort, older smokers (aged ?55 years) who received varenicline did not have a greater point-prevalence abstinence after 6 months compared with those who used NRT patch or gum. Younger smokers (aged 25-54 years) who received varenicline had a greater likelihood of abstinence than NRT users. Sex and nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT patch or gum. Age-appropriate approaches for effective tobacco control are needed.

Project description:BackgroundVarenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10-week standard regimen of transdermal nicotine replacement therapy (NRT) for smoking cessation.MethodsIn this 52-week, open-label, randomised, multicentre, phase 3 trial conducted in Belgium, France, The Netherlands, UK and USA, participants were randomly assigned (1:1) to receive varenicline uptitrated to 1 mg twice daily for 12 weeks or transdermal NRT (21 mg/day reducing to 7 mg/day) for 10 weeks. Non-treatment follow-up continued to week 52. The primary outcome was the biochemically confirmed (exhaled carbon monoxide < or = 10 ppm) self-reported continuous abstinence rate (CAR) for the last 4 weeks of the treatment period in participants who had taken at least one dose of treatment. Secondary outcomes included CAR from the last 4 weeks of treatment through weeks 24 and 52, and measures of craving, withdrawal and smoking satisfaction.ResultsA total of 376 and 370 participants assigned to varenicline and NRT, respectively, were eligible for analysis. The CAR for the last 4 weeks of treatment was significantly greater for varenicline (55.9%) than NRT (43.2%; OR 1.70, 95% CI 1.26 to 2.28, p<0.001). The week 52 CAR (NRT, weeks 8-52; varenicline, weeks 9-52) was 26.1% for varenicline and 20.3% for NRT (OR 1.40, 95% CI 0.99 to 1.99, p = 0.056). Varenicline significantly reduced craving (p<0.001), withdrawal symptoms (p<0.001) and smoking satisfaction (p<0.001) compared with NRT. The most frequent adverse event was nausea (varenicline, 37.2%; NRT, 9.7%).ConclusionsThe outcomes of this trial established that abstinence from smoking was greater and craving, withdrawal symptoms and smoking satisfaction were less at the end of treatment with varenicline than with transdermal NRT.Trial registration numberNCT00143325.

Project description:Background and aimsThe phase-based model of smoking cessation treatment suggests that treatment needs may vary across phases (e.g. pre-cessation, cessation). This study tested the comparative effects of varenicline and combination nicotine replacement therapy (C-NRT) relative to nicotine patch monotherapy on pre-cessation and cessation phase candidate withdrawal, expectancy and motivation mediators; relations between mediators and abstinence; and indirect effects of enhanced treatments on abstinence via candidate mediators.DesignSecondary mediation analysis of data from the open-label, randomized Wisconsin Smokers' Health Study 2, a comparative effectiveness trial of varenicline or C-NRT, versus patch monotherapy, in adults who smoked, recruited via media and community outreach.SettingResearch clinics in Madison and Milwaukee, Wisconsin, USA.ParticipantsA total of 1051 daily smokers motivated to quit smoking (52.5% female; mean age = 48.1, standard deviation = 11.6).InterventionsTwelve weeks of varenicline (n = 407) or 12 weeks of combination nicotine patch and nicotine lozenge therapy (n = 421), both compared with 12 weeks of patch control condition (n = 230), with individual smoking cessation counseling.MeasurementsThe primary abstinence outcome was biochemically verified 7-day point-prevalence abstinence 4 weeks post-target quit day (TQD). Candidate mediators (craving, positive smoking expectancies, withdrawal symptoms, and quitting motivation) were assessed via ecological momentary assessment from 1 week prior (pre-cessation phase) to 4 weeks after (cessation phase) the TQD.FindingsPre-cessation and cessation mean levels and slopes of craving [adjusted odds ratio (aOR) = 0.34-0.79], smoking expectancies (aOR = 0.46-0.79) and quitting motivation (aOR = 1.35-7.21) significantly predicted 4-week post-TQD abstinence (P < 0.05). Significant varenicline mediation occurred via greater suppression in pre-cessation craving [mediated effect (ab) = 0.09, standard error (SE) = 0.03, 95% confidence interval (CI) = 0.04-0.14] and smoking expectancies (ab = 0.06, SE = 0.02, 95% CI = 0.02-0.12). C-NRT mediation occurred via greater reduction in pre-post-TQD changes in craving (ab = 0.04, SE = 0.02, 95% CI = 0.01-0.08) and expectancies (ab = 0.03, SE = 0.02, 95% CI = 0.001-0.07), relative to patch monotherapy.ConclusionAmong adult smokers seeking to quit, varenicline seems to work through its effects on suppression of craving and smoking expectancies pre-cessation while combination nicotine replacement therapy mediation seems to work through cessation-related reduction in craving and smoking expectancies changes.