Every internist agrees that cigarette smoking is harmful for patients. But in terms of the safety of electronic nicotine delivery systems (aka e-cigarettes) and their potential role in smoking cessation, inconsistent data have divided expert opinions and stymied clinical consensus.
Despite the disagreement, internists may encounter patients who, after having little success with FDA-approved nicotine replacement therapies (NRTs), ask if e-cigarettes could help them quit smoking. In June, James S. Yeh, MD, MPH, ACP Member, presented this clinical scenario in the New England Journal of Medicine, which featured a “for” perspective, an “against” perspective, and an informal readership poll. Of 666 poll respondents, two-thirds voted to recommend the use of e-cigarettes for smoking cessation, whereas the others voted against recommending their use.
The case vignette is more than hypothetical quandary, as an increasing number of patients over the past couple of years have asked for clinical opinions on e-cigarettes, said Dr. Yeh, a physician at Massachusetts General Hospital and an instructor in medicine at Harvard Medical School in Boston. “It seems like e-cigarettes hold promise, but at the same time, we don't really know anything about their safety. It is important to continue to emphasize with patients the iterative process of quitting smoking with the current standard of smoking cessation strategies,” he said.
As researchers attempt to clear the air, however, one theme consistently emerges in favor of e-cigarettes: reducing the harm caused by tobacco. Yet, even in the wake of recent FDA regulation, experts agreed that the dearth of long-term safety evidence makes e-cigarettes an impracticable smoking cessation strategy, at least for now.
Harm reduction and efficacy
The U.K.'s Royal College of Physicians in April provided perhaps the most eminent show of clinical support for e-cigarettes to date. For all their potential harms, the devices should be promoted widely as a replacement for cigarettes and are likely to benefit public health, the group concluded in its report.
In terms of evidence for harm reduction, the current best estimate is that e-cigarettes are about 95% less harmful than tobacco cigarettes, according to the report. The estimate stems from a 2014 study, published in European Addiction Research, comparing the overall harms, including mortality, of 12 different nicotine products. NRTs (e.g., nasal sprays, oral products, and patches) are even safer than e-cigarettes, posing negligible harm in comparison to cigarettes, the international panel of experts determined.
Jonathan Foulds, PhD, a coauthor of the paper, pointed out that 5% of the 480,000 annual premature deaths in the U.S. due to smoking still equals 24,000 deaths. “If you look at it that way, it's definitely not saying that these things are harmless; it's just saying that they're a lot less harmful than the currently dominant product,” said Dr. Foulds, a professor of public health sciences and psychiatry at Penn State University College of Medicine in Hershey, Pa.
Unsurprisingly, the study drew both support and vitriol from clinicians and public health experts. “There's a lot of heat on the topic,” Dr. Foulds said, “unfortunately much more heat than there is light (data).”
The data that do exist on the efficacy of e-cigarettes mostly come from abroad, with 1 of the most recent studies published online on Sept. 13 by The BMJ. Researchers correlated England's jump from 2006 to 2015 in successful quit rates (from about 11% to 19%) to the increasing prevalence of e-cigarette use among smokers (from a negligible amount to about 21%). During this time, the use of prescription-based NRTs dropped significantly, the time-series analysis found.
In addition, patients seem to prefer e-cigarettes over the nicotine inhaler, according to a study published in 2014 in the Journal of General Internal Medicine. In the crossover trial, smokers who had never used NRT used each product for 3 days before answering survey questions.
“E-cigarettes scored consistently higher than the inhaler in satisfaction and reward, acceptability, ‘cooler’ image, and perceived helpfulness in quitting smoking. In addition, despite a lack of evidence regarding safety and effectiveness, over three-quarters of participants said they would use the e-cigarette to quit smoking, compared to less than one-quarter for the FDA-approved nicotine inhaler,” said lead author Michael Steinberg, MD, MPH, FACP, professor and chief of the division of general internal medicine at Rutgers Robert Wood Johnson Medical School in New Jersey.
In terms of clinical trials, the best-designed study to date was published in 2013 in The Lancet, according to Dr. Foulds. Researchers found e-cigarettes to be slightly better than the nicotine patch in promoting abstinence among smokers, but the effects were only modest. “The e-cigarette used in the trial delivered very little nicotine,” Dr. Foulds said. “It's not surprising that it didn't get a very high quit rate.”
That's one of the problems with research in this area: “No single randomized controlled trial has studied an e-cigarette that has been demonstrated to have good nicotine delivery before the trial,” said Dr. Foulds, although he is in the process of doing that with colleagues at the Tobacco Centers of Regulatory Science at Virginia Commonwealth University in an ongoing randomized placebo-controlled trial of e-cigarettes to reduce cigarette consumption.
Most of the researchers in the tobacco control field would agree that those who switch entirely from smoking cigarettes to using e-cigarettes are probably reducing the harms they're being exposed to, Dr. Steinberg said. “But it's a much more complicated picture than that. … I think we really need some more traditional scientific evidence that shows that e-cigarettes are effective at helping people stop using tobacco cigarettes before we can start proposing them as a cessation method,” he said.
In addition to the question marks surrounding e-cigarettes' viability as a smoking cessation strategy, there is also scant long-term safety evidence because of their relatively recent popularity. In May, the FDA deemed e-cigarettes to be under its regulatory authority as a tobacco product.
Regulation means some positive effects, such as ensuring ingredient transparency, but it's not likely to facilitate clinical trials, Dr. Foulds said. As soon as an e-cigarette product makes a therapeutic claim, it will jump into the regulatory hands of the FDA Center for Drug Evaluation and Research and have to go through the years-long process of being licensed as a medication, he said. “In the meantime, technology will have moved on,” and any licensed e-cigarettes would have to compete against those already on the market, Dr. Foulds said.
So it doesn't appear that doctors will get gold-standard clinical evidence any time soon. Because of this, Dr. Steinberg recommends that physicians continue to inform patients that the best way to quit is to use FDA-approved, proven tobacco treatment methods, such as NRT, varenicline, or bupropion. But for patients who are able to stop smoking by using e-cigarettes, he recommends being supportive.
“In those people, we don't tell them, ‘Stop your e-cigarettes, this is bad.’ We say, ‘You've probably improved your health and reduced your harm, and we're here to support you. You can continue to use what's been helpful for you,’” Dr. Steinberg said.
Dr. Foulds recommended the same, noting that pharmacotherapies like varenicline may be even more effective when combined with NRTs and behavioral counseling.
“It's a tricky position for doctors. Unfortunately, I think because of the lack of the usual data on which a doctor relies, there's a tendency for some to say they're not safe, they may be harmful, etc.,” he said. “So people are not getting advice from clinicians to use them; they're just using their own common sense and word of mouth from other people who are using them successfully.”
Still, considering the paucity of safety data, Dr. Yeh said there must be an abundance of caution among internists. “But at the same time, I'm hopeful for the promises that these kinds of devices have, especially if they're proven to be effective and safe,” he said.
For Dr. Foulds, the hope for e-cigarettes is far-reaching. “To my mind, people smoke for nicotine. They like cigarettes because it's an easy way to get very rapid nicotine absorption, and now that we know that some of these e-cigarettes can do that, in my opinion, these e-cigarettes could replace cigarettes,” he said.
More evidence is coming, said Dr. Steinberg, including his own work surveying 2,000 physicians on a yearly basis for the next 3 years to assess how their communications with patients about e-cigarettes change over time. “I think 3 years from now, we're going to have a much different perspective on whether these products really are effective at helping people quit smoking or not,” he said.