A clinical trial to test whether three proven smoking cessation treatments could also reduce alcohol intake found no differences between the medications, but the rates of behaviour change for alcohol consumption and smoking were high in all treatment groups.
Results suggest these medications could play an important role to reduce alcohol use and smoking at the same time. Unexpectedly, nicotine replacement therapy performed as well as the prescription drugs varenicline and cytisine.
The study, published in JAMA Network Open, involved 400 people living with HIV in Russia and was designed by researchers from Vanderbilt University Medical Center (VUMC), Boston University School of Medicine, Boston Medical Center and First Pavlov State Medical University of St. Petersburg, Russia. The investigators, who included addiction specialists and HIV researchers, recruited volunteers who self-identified as engaging in risky drinking and daily smoking. Participants were followed up to 12 months after enrolment in the clinical trial. Medications were placebo-controlled, so participants and investigators did not know who was assigned to which medication.
The study showed that after three months, alcohol consumption decreased regardless of whether participants were given nicotine replacement therapy, varenicline or cytisine. The main outcome was number of heavy drinking days in the past month at three months, and secondary outcomes included abstinence from alcohol at three months, and abstinence from smoking at six months.
“A single medication to treat both risky drinking and smoking could improve health efficiently and significantly. Risky drinking and smoking frequently co-occur, and they both threaten health by increasing risk of cardiovascular disease, cancer and other important health outcomes,” said the study’s lead author, Dr Hilary Tindle, MPH, the William Anderson Spickard, Jr. MD Professor of Medicine, and associate professor of Medicine at VUMC.
Researchers are increasingly focusing on comorbidities among people living with HIV, such as cardiovascular disease and cancer, to improve their longevity because there are now effective treatments for the virus.
“It was gratifying to see high-risk research participants being included in NIH-funded research,” said Dr Matthew Freiberg, MSc, a study principal investigator, Dorothy and Laurence Grossman Chair in Cardiology and professor of Medicine at VUMC. “They are not only living with HIV, but also have a high burden of hepatitis, multi-substance use and mental health issues. Such participants are often excluded from drug trials. If a medication as simple as nicotine replacement could help them, that would be a win.”
Freiberg noted that when investigators had designed the study, they envisioned the nicotine replacement as the “control” arm for alcohol consumption. Nicotine replacement therapy has been available in the United States to treat tobacco addiction since the early 1980s and is not used for reduction of alcohol consumption.
The study enrolled participants who engaged in five or more heavy drinking days in the past month (defined as five or more drinks in one day for a man or four or more drinks in one day for a woman) and who smoked five or more cigarettes a day.
VUMC researchers worked with Dr Jeffrey Samet, MA, MPH, the John Noble, MD, Professor in General Internal Medicine and professor of Community Health Science at Boston University Schools of Medicine and Public Health, and colleague on the study. Samet’s research focuses on substance abuse and HIV infection.
“Another important observation in our post-hoc analysis was that rates of alcohol consumption were lower, and rates of alcohol abstinence were higher, among the people who quit smoking, compared with those who continued to smoke. These results need further study to understand if findings were due to the medications directly, quitting smoking or both,” said Samet, the senior author on the study.
Tindle added that there is much to be learned about how the study drugs – termed nicotinic acetylcholine receptor agonists – may work to reduce voluntary alcohol intake. Studies in animal models show that stimulation of a very specific receptor type containing the alpha four subunit is required. Importantly, all three of the study medications target these very receptors.
The investigators concluded that the results of the study, conducted from July 2017 to December 2020, extends prior work in several ways. Notably, this is the largest trial to study nicotinic acetylcholine receptor partial agonists to target alcohol consumption and the first to examine cytisine to treat both alcohol and tobacco. Cytisine is not yet approved by the US Food and Drug Administration to treat tobacco use but it has been used widely in Eastern Europe for decades and is under active study globally.
The study received funding from the National Institute on Alcohol Abuse and Alcoholism in support of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS, the Providence/Boston Center for AIDS Research and the Tennessee Center for AIDS Research.
Study details
Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use: A Randomised Clinical Trial
Hilary A. Tindle, Matthew S. Freiberg, Debbie M. Cheng, Natalia Gnatienko, Elena Blokhina, Tatiana Yaroslavtseva, Sally Bendiks, ; Gregory Patts, Judith Hahn, P Kaku So-Armah, Michael Stein, Kendall Bryant, Dmitry Lioznov, Evgeny Krupitsky, Jeffrey H. Samet,
Published in JAMA Network Open on 5 August 2022
Key Points
Question Are varenicline and cytisine more efficacious than nicotine to treat alcohol and smoking among individuals who smoke daily, have HIV, and engage in risky drinking?
Findings This randomised clinical trial of 400 individuals with HIV who engaged in risky drinking and daily smoking found that alcohol consumption at three months was decreased in all groups (active varenicline and placebo nicotine replacement therapy [NRT], placebo varenicline and active NRT, active cytisine and placebo NRT, and placebo cytisine and active NRT) but heavy drinking days did not differ significantly by group. Smoking abstinence at 6 months did not differ by group, but abstinence rates were high.
Meaning This study found that varenicline and cytisine were not more efficacious than nicotine to treat risky drinking and smoking but that rates of behaviour change for alcohol consumption and smoking were high in all treatment groups, suggesting a role for these medications in individuals who report risky drinking and smoking.
Abstract
Importance
Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions.
Objective
To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT.
Design, Setting, and Participants
This four-group randomised, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrolment. Data were analysed from May 2021 through June 2022.
Interventions
Participants received alcohol and tobacco counselling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4).
Main Outcomes and Measures
The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months.
Results
Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking.
Conclusions and Relevance
This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behaviour change rates were high in all groups.
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