Nicotine e-cigarettes, counseling aid smoking cessation in randomized trial

Mark J. Eisenberg

In the randomized E3 trial, nicotine e-cigarettes combined with individual counseling was more effective for smoking cessation at 12 weeks than non-nicotine e-cigarettes with counseling or counseling alone.

Mark J. Eisenberg, MD, MPH, professor of medicine at McGill University in Montreal, presented results of the 376-participant randomized trial. Adults who were randomly assigned to nicotine e-cigarettes and smoking-cessation counseling were more likely to continue to abstain from smoking at 12 weeks than those who received counseling only (21.9% vs. 9.1%; RR = 2.5; 95% CI, 1.3-4.6).

Moreover, participants assigned non-nicotine e-cigarettes with individual counseling were also more likely to abstain from smoking compared with those assigned counseling alone (17.3% vs. 9.1%; RR = 1.9; 95% CI, 1-3.8), but less likely than the nicotine e-cigarette arm.

Additionally, participants assigned nicotine e-cigarettes smoked a mean difference of 5.7 fewer traditional cigarettes per day (95% CI, –8 to –3.3) vs. counseling, and those who received non-nicotine e-cigarettes smoked a mean difference of 3.6 fewer per day (95% CI, –6.3 to –1) vs. counseling.

“Nicotine e-cigarettes with individual counseling for 12 weeks is efficacious for smoking cessation compared to counseling alone,” Eisenberg said. “Non-nicotine e-cigarettes with individual counseling has benefits, which appear to be intermediate between those of nicotine e-cigarettes with counseling and counseling alone.”

During the trial treatment period, few serious adverse events occurred. These included one respiratory event (chronic obstructive pulmonary disease exacerbation) in the nicotine e-cigarette arm; one cardiac event (MI) and four other events in the non-nicotine e-cigarette arm; and two other events in the counseling arm. All serious adverse events were adjudicated by the endpoints evaluated committee as deemed unrelated to the treatment participants received. Eisenberg noted that the E3 trial was not powered to look at statistical differences in adverse events.

“Very few serious adverse events occurred during the 12 weeks; however, there clearly remains a need for additional safety data,” Eisenberg said.

Participant enrolled in the E3 trial reported smoking an average of 21 traditional cigarettes per day for 35 years. The mean age at baseline was 53 years. Participants reported their smoking cessation progress via three phone calls and two clinic visits over 12 weeks. Carbon monoxide breath tests verified smoking abstinence.

“Longer-term follow-up data from the E3 trial will help determine if the benefits that we saw will persist over time,” Eisenberg said.

Six- and 12-month follow-up data will be reported in the future, according to Eisenberg.

“As clinicians, we are certainly struggling with whether to recommend e-cigarettes to promote smoking cessation because we have a lack of real data to support whether there’s a clear benefit to this strategy in improving those outcomes,” Eugene Yang, MD, MS, FACC, professor of medicine at the University of Washington School of Medicine, said during a virtual panel discussion.

He noted that a concern is “whether we are really substituting one bad habit for another bad habit.”

“This study clearly shows a small benefit with short-term follow-up at 12 weeks. The intent was to have 52-week follow-up, which you are now conducting. But as we know, the relapse rates are high for those individuals at both 6 and 12 months, and so getting that additional information will certainly be beneficial,” Yang said. – by Scott Buzby

Reference:

Eisenberg M, et al. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 28-30, 2020 (virtual meeting).

Disclosures: Eisenberg and Yang report no relevant financial disclosures.

Editor’s note: This article was updated on April 3, 2020, to correct the data on smoking abstinence at 12 weeks. The Editors regret the error.

PERSPECTIVE

Martha Gulati, MD, MS, FACC, FAHA, FASPC

The findings are interesting, but do not answer whether this is the magic that we’ve been looking for to help people quit smoking. I would call this preliminary data hopeful, but there are a lot of missing pieces.

When patients use e-cigarettes to quit smoking, I don’t know what’s in the e-cigarette. Additionally, my question is whether I am replacing one form of nicotine for another?  And is it safer? And nicotine is addictive, so how will I wean them off e-cigarettes?  What’s the long-term safety of using an e-cigarette? And will this truly be better than other smoking cessation aids we have available? We cannot tell this from 12 weeks of data. And if the  participants use e-cigarettes for 52 weeks, there is the potential to addict them to e-cigarettes for life. I can’t tell them that is OK.

As a health care community, we are terrible at getting people to quit smoking, despite having different drugs and other techniques that we can use to help. The counseling part is always necessary. When we use counseling, we know that is a way to keep patients engaged; they feel like they can talk about the symptoms that they have; if they do fail to quit smoking, using whatever methodology, we can always reset the button and see why they failed. And don’t forget that every arm of this study did include counselling.

A big reason for our poor performance on smoking cessation is our health care system. It’s hard to get reimbursed for preventive therapies or the kind of counseling that was offered in this study. As a community, we really need to invest in prevention. As a preventive cardiologist, I always say we do sick care really well, but we don’t do health care very well.

These data will not change my personal clinical practice. I work with my patients to help them quit smoking, but with e-cigarettes there are a lot of unknowns. This year, all we’re talking about is COVID-19, but last year what we were concerned about was e-cigarettes, especially in young people, and the associated lung effects. That’s taken a back seat to everything else going on, and rightfully so, but we can’t forget that we don’t know what people are inhaling.

E-cigarette companies were probably worried that this study wouldn’t come out in their favor. I have always believed that if a company wants to promote a product, then it should give unrestricted research grants to the right investigators to try to show that the product does what the company thinks it does. These companies should put their money where their mouth is and they should want these studies if they want people to use their products.

Martha Gulati, MD, MS, FACC, FAHA, FASPC
Division Chief of Cardiology
University of Arizona College of Medicine – Phoenix
Physician Executive Director
Banner – University Medicine Heart Institute, Phoenix
Editor-in-Chief
American College of Cardiology’s CardioSmart
Disclosures: Gulati reports no relevant financial disclosures.

PERSPECTIVE

B. Hadley Wilson, MD, FACC

The investigators are to be congratulated for the first large-scale study of this kind on the effects of e-cigarettes on smoking cessation. It was very interesting that in this 12-week period combined with counseling, e-cigarettes were effective in achieving smoking cessation in a significant number of patients with few adverse events. It was also interesting that e-cigarettes without nicotine were also effective, though somewhat less so. The study only went for 12 weeks, so it will be important to see if compliance with smoking cessation is durable with e-cigarettes and counseling. It certainly appears to be a step in the right direction, and further study is warranted.

B. Hadley Wilson, MD, FACC
Executive Vice Chair, Atrium Health’s Sanger Heart & Vascular Institute
Clinical Professor of Medicine, UNC School of Medicine
Chair, Membership Committee
American College of Cardiology Board of Trustees
Disclosures: Wilson reports no relevant financial disclosures.