A Q&A on Smoking Cessation With E-Cigarettes, REDUCE-IT Trial Findings

The American Journal of Managed Care^® (AJMC^® ) interviewed Martha Gulati, MD, cardiologist at Banner — University Medicine Heart Institute, on 2 late breaking clinical trials titled, “A Randomized Controlled Trial Evaluating The Efficacy And Safety Of E-Cigarettes For Smoking Cessation,” and “Eicosapentaenoic Acid Levels in REDUCE-IT and Cardiovascular Outcomes.”

The trial findings were released through the American College of Cardiology (ACC) and World Congress of Cardiology (WCC) Annual Meeting—ACC.20/WCC Virtual Experience.

AJMC^®: Based on study findings from smoking cessation with e-cigarettes (ECs), participants who received smoking cessation counseling and used ECs containing nicotine were more than twice as likely to successfully quit smoking compared with those who received counseling but did not use EC. As the long term health effects of ECs remain unknown, what factors come into play when considering vaping as a potential approach for patients?

Gulati: It's funny, before the coronavirus disease 2019 (COVID-19) crisis, we were talking about the vaping crisis—much gentler times because you used to think well, we could just stop vaping.

How much more beneficial? I think there's 2 concerns. One, the study I would take with a grain of salt because it was only short term. So, 12 weeks is great, and it's a celebrated success of quitting smoking for sure, but it's only 12 weeks. It's always long-term follow-up that really tells us if people can really quit. So, long-term, if you continue to use ECs, we still don't know the safety as the authors of this study pointed out nicely.

The concerns I have with ECs is the long term effects and short term effects of vaping, and a lot of it is us not knowing what's in the vaping substances. People were given ECs, but it's not like they controlled the content aside from 1 being nicotine and 1 being non-nicotine. When people go out to buy ECs, as my patients tell me they're using them to help them quit, the problem is I don't know what's in them. In general, none of us do.

We don't know the agents, we don't know the cancerous substances that can be in there, and we also don't know the aerosolized particles and the damage because that's what had been happening just a few short months ago when we were all talking about vaping, and how our younger population was dying from vaping. So, I think that if we're going to use these substances, knowing what is being put into these products would be far more helpful.

AJMC^®: How should physicians optimally implement vaping into smoking cessation?

Gulati: I think that I want more data before I would implement vaping. If somebody tells me that they're going to do it anyway, I'm of course going to support them. When I start smoking cessation counseling, which happens at every visit for a smoker for me, we talk about cigarettes—we talk about the effect on the heart and overall health. Then we talk about is this the time that you want to talk about quitting? If they do, we talk about the options. ECs often come up because of both the way that they're presented and the way that they sort of feel like a cigarette, and a lot of people think if I do it this way, I can quit smoking.

I always hesitate encouraging it unless it's the only option they're willing to consider because we have limited data on safety; but, again, I don't want to discourage a patient if this is the only thing that they are willing to consider, I will work with them to make it work. The other thing I think we need to work on is, and other studies hopefully will answer this, is if you use ECs, how long are you using them for? Is it for the rest of your life? Or is it going to be something just like when we use other substances to help people quit that we slowly wean them off of it.

If we can't wean them off of it, ECs are expensive and there's untold consequences. I don't know which one's worse—the cigarette or the EC yet because I don't have the data. So, that's always the issue that you have to work out with your patient, but of course, we're partners with our patients. This is shared decision-making, and we talk about what we know and what we don't know together as a patient and a physician, trying to make the best choice for the person in front of us. I think that's always how it will work until we have more data.

AJMC^®: REDUCE-IT findings indicated that higher levels of omega-3 fatty acid eicosapentaenoic acid (EPA) in the blood, as opposed to lower levels as initially thought, were associated with a significant reduction in cardiovascular events and deaths. Can you explain the significance of this finding?

Gulati: Dr. Bhatt’s findings are really interesting because there was 1 slide where he showed triglyceride lowering and how much it was associated with outcomes, but it's more than just triglycerides was the message that I got, because although we know the way that fish oil, at least 1 of the many things it does is it reduces triglycerides; but even by the measured level of EPA in the blood, it seems to have an association that for every unit, and I guess that unit was 1 microgram per milliliter—there was a about a 2% reduction in the end points for the study.

So, there's something mechanistically explaining about the EPA maybe, because we really don't know how fish oil works. So, mechanistically maybe explaining both why this drug was successful compared to other fish oils and what it might be doing—that there's something about EPA that is working. We know EPA versus some other forms of fish oil that have EPA and DHA [docosahexaenoic acid], and DHA seems to work perhaps more in the brain and EPA seems to be more targeted towards the vascular system. Again, the EPA levels that are circulating seemed, I don't know if we can say definitively, but seemed to have a role by circulating in the system, probably reducing inflammation, improving basal dilation, and potentially working to reduce cardiovascular events.

AJMC^®: As studies continue to examine the mechanisms behind icosapent ethyl in association with cardiovascular events, what factors still warrant further investigation?

Gulati: EPA levels didn't didn't tell us exactly the mechanism, it just said EPA is floating around here, right? It's in the circulation, but all the other parts of it are sort of hypothesized. We have animal studies, but we don't yet have human studies entirely showing the relationship with inflammation and other mechanistic pathways. So, it’s just saying, if we have EPA levels that are elevated, we're thinking this is what's going on, because it at least has some potential impact on the event.

So, we certainly need to know more about what that circulating EPA does. I think that the other question that this study brings up is—somebody asked a really good question at the end, 1 of the moderators asked, is more EPA better? Should we be both targeting levels of EPA or even giving potentially more? The answer is we don't know–that's what Dr. Bhatt said as well. We just don't know because we don't have those studies. This was a study of giving this form of fish oil, 4 grams total in a day, of this form of EPA.

We just don't know if we give more, both the safety profile, as well as the cardiovascular effect profile. I think 1 of the important things that I think for my patient that comes up on a regular basis is, so then can I just take any fish oil? Like over the counter or otherwise. This is a very different form—this prescription form is very different from the form that you get over the counter. You would have to take so many numbers of pills to even get this amount of EPA. So, I don't encourage people to think that they can somehow do this with supplements, they can't.

This same question comes up for patients: can I just eat fish? Again, I remind people that yes, fish can be beneficial, but that wasn't in this study. These were people who were higher risk patients based on the enrollment criteria for REDUCE-IT, and this is beyond diet. Diet alone also wouldn't get EPA levels to this level. So, not to discourage people from eating fish and maintaining a healthy diet with a more Mediterranean type of focus, but if you meet the criteria to get into REDUCE-IT, then this is the drug you should be taking.