E-Cigarettes Added to Counseling Can Help Smokers Quit at 12 Weeks
Results from the E3 trial hint that e-cigs are beneficial, but longer-follow-up and studies on more-current devices are needed.
Tobacco smokers who receive e-cigarettes in addition to counseling are twice as likely to quit by 12 weeks, according to data from the multicenter, randomized E3 trial. This benefit is seen even when the e-cigarettes don’t contain nicotine, though to a smaller degree.
With nicotine e-cigarettes, 22% of individuals quit smoking standard cigarettes. Without nicotine, the proportion was 17%, still higher than the 9% of patients given counseling alone.
“The long-term health effects of inhaling combustible tobacco are well established. However, even with the use of pharmacologic or behavioral therapy, well over two-thirds of those attempting to quit return to smoking within 1 year,” said Mark J. Eisenberg, MD (Jewish General Hospital, Montreal, Canada), reporting the results Monday at the virtual American College of Cardiology 2020 Scientific Session.
Some of the concerns clearly that we have in the clinical domain are whether we are substituting one bad habit for another bad habit. Eugene Yang
Many smokers have turned to e-cigarettes as a potential cessation aid, he said, but little is known about the efficacy and safety of this strategy. What’s key, though, is that these 12-week results are just the first piece of the puzzle—several experts, including Eisenberg himself, pointed to the need for longer-term follow-up.
E-Cigarettes, With or Without Nicotine
E3 enrolled 376 people (mean age 52 years; 53% men) at 17 sites in Canada. On average, these individuals had smoked around 21 cigarettes a day for 35 years prior to the study. All were considered motivated to quit, in that 91% had tried before but failed. Most had already tried smoking cessation medications or behavioral therapy, and around a third had tried e-cigarettes.
The researchers randomly assigned participants to one of three groups: e-cigarettes with nicotine, e-cigarettes without nicotine, or counseling alone. People in the first two groups were given a closed-system NJOY rechargeable device with tobacco-flavored refill cartridges containing 15 mg/mL nicotine or identical cartridges without nicotine.
Over the 12-week study period, all received around 100 minutes of counseling that encouraged quitting. Participants self-reported their progress during three phone calls. Twice during the 12 weeks, they visited a clinic to undergo a breath test for carbon monoxide to confirm whether they had or hadn’t smoked.
People who reported not smoking at all and also passed the breath test were judged to have quit.
Dropout was more common in the counseling-only group, which Eisenberg said is expected, since many participants had enrolled with the hope of receiving e-cigarettes. Analyses were intention-to-treat and done under the assumption that any participants who dropped out of the trial returned to smoking.
With nicotine e-cigarettes, there was a 12.8% absolute difference in 12-week quit rates compared with counseling alone (RR 2.4; 95% CI 1.3-4.6). Without nicotine, the e-cigarette group was 8.2% more likely to quit than the counseling group, not quite a significant difference (RR 1.9; 95% CI 1.0-3.8).
Even those who didn’t fully quit made some progress. Compared to the baseline of 21 cigarettes, people given nicotine e-cigarettes smoked eight times per day and those who vaped without nicotine did so 10 times daily. Counseling alone brought the number down to 14.
A much more rigorous measure of smoking cessation, Eisenberg noted, is “continuous abstinence,” where any cigarette use at any time point is counted as not quitting. At all points, the e-cigarette groups did slightly better than the counseling-only group with regards to this endpoint. By 12 weeks, continuous abstinence was seen in 5% of the nicotine e-cigarette participants, 3% of those given nicotine-free devices, and 1% of those who had counseling.
Side effects were few, though one man in the nicotine e-cigarette group experienced worsening of his chronic obstructive pulmonary disease. One participant assigned to receive nicotine-containing e-cigarettes experienced an exacerbation of chronic obstructive pulmonary disease.
Eisenberg pointed out that, because of a manufacturing delay in e-cigarettes, the researchers halted enrollment at 77% of their target. To deal with this reduction in statistical power, they then shortened the study from its planned 52-week follow-up, instead analyzing the primary endpoint at the end of the 12-week treatment period. Six- and 12-month data are still forthcoming, Eisenberg reported, and “will help determine if the benefits persist over time.”
Notably, E3 had already begun before cases of e-cigarette or vaping-related lung injury (EVALI) began being widely reported; none occurred within the confines of the study.
E-cigarettes as used in E3, though, wouldn’t be expected to cause this problem, Eisenberg told TCTMD. “EVALI appears to be related to adulteration of e-cigarette liquid with cannabis and vitamin E acetate. We used an e-cigarette with a closed-tank system so there was no chance of adulterating the liquid.”
A Longer Horizon Needed
During the late-breaking session, panelist Nancy Rigotti, MD (Massachusetts General Hospital, Boston, MA), described E3 as addressing a critical evidence gap on e-cigarettes’ efficacy for smoking cessation. Its main limitation is the short follow-up period, she stressed.
“Twelve weeks is really the ‘end of treatment’ point,” Rigotti observed. “We know that relapse after quitting is very common, and the norm for smoking cessation trials is to present at least 6 months of follow-up and ideally 12 months of follow-up to be sure that the effect of the intervention holds long-term and leads to permanent cessation.”
She also pointed out that e-cigarettes are a fast-moving industry, so the device tested in E3 is no longer current. “The best-selling products are now the pod mod devices, which are exemplified by Juul products and others. These deliver a higher dose of nicotine and [probably] do so more rapidly than the product that was tested,” Rigotti noted.
To Eisenberg, she raised the possibility that the results might differ if Juul had been the e-cigarette studied.
“My father was a doctor—he told me he liked to see 10 different studies in 10 different patient populations with 10 different products before he would consider accepting the results,” he replied.
It would be great, Eisenberg agreed, to know how the latest generation of e-cigarettes would perform. Yet, he said, “I think it might be problematic ethically to do this kind of study with Juul. We’re open to doing that; we actually contacted them at the beginning of this and they didn’t even want to talk to us to do a trial. But I think it’s important information and I’d like to see it as well.”
Asked by TCTMD about these ethical concerns, Eisenberg explained: “Regarding Juul, they have captured the majority of the e-cigarette market in the US. There are some ethical issues with doing e-cigarette trials. Many of the companies have been purchased by tobacco companies and researchers are reluctant to be involved [with them].”
Press-conference discussant Eugene Yang, MD (University of Washington School of Medicine, Seattle), said that clinicians are struggling with whether to recommend e-cigarettes for smoking cessation. “Some of the concerns clearly that we have in the clinical domain are whether we are substituting one bad habit for another bad habit,” he observed, citing emerging data about e-cigarettes perhaps increasing the risks of pulmonary disease and cardiovascular events.
Long-term follow-up will provide clarity not only on efficacy but also any safety concerns that could emerge, Yang told the media. An “area of opportunity” would be to compare e-cigarettes against US Food and Drug Administration-approved approaches like nicotine replacement therapy or medications that have already proven beneficial.
Eisenberg MJ. A randomized controlled trial evaluating the efficacy and safety of e-cigarettes for smoking cessation. Presented on: March 30, 2020. ACC 2020.
- Eisenberg reports no relevant conflicts of interest.