Varenicline Boosts Long-term Quit Rate in Post-ACS Smokers: EVITA

Smokers who are hospitalized for ACS may be especially receptive to advice on how to quit and to tools for keeping themselves off cigarettes. Now, research published online today in CMAJ shows that patients with MI and unstable angina who start taking a 12-week regimen of the antismoking drug varenicline (Chantix; Pfizer) during their hospital stay are significantly more likely to not smoke by 1 year compared with those given placebo.

Long-term data from the randomized EVITA trial show a nearly 11% absolute difference in 1-year quit rates between the two groups. Still, even among those on drug therapy, six in 10 individuals continued to smoke, report Sarah B. Windle, MPH (Jewish General Hospital, McGill University, Montreal, Canada), and colleagues. Six-month follow-up from the trial was reported by TCTMD back in 2015.

The absolute difference seen in the latest analysis “is huge,” senior author Mark Eisenberg, MD (Jewish General Hospital, McGill University), commented to TCTMD. Given that “it’s very, very difficult to quit,” it’s not surprising that most patients failed to do so, he said, pointing out that individuals who agreed to participate in the study were highly motivated. In the real world, quit rates would likely be even lower, Eisenberg predicted.

Eisenberg, an interventional cardiologist, said that initially he wasn’t convinced varenicline would work so well but now he sees ACS as a window of opportunity for smoking cessation.

“I was not doing this. I wanted to see the results of the trial,” he acknowledged. “I now think that when I’m doing an angioplasty at 3 o’clock in the morning, somebody with acute MI, and I actually type into the computer their prescription for aspirin and Plavix, that I should write a prescription for varenicline to start right away in everybody.”

A multidisciplinary approach that starts in the hospital is best, Eisenberg stressed. “Most cardiologists don’t feel they’re competent to give smoking cessation, so they don’t even want to open up that can of worms.” The important thing here is that even in a trial designed to involve very little counseling, the drug therapy was beneficial, he explained.

“It’s an important message for interventional cardiologists. We could be the bandleaders here, because we’re the ones [treating them acutely],” Eisenberg advised.

Quinn R. Pack, MD (Baystate Health, Springfield, MA), also a cardiologist, said varenicline is the only evidence-based therapy he knows of that can help people stop smoking post-MI. The 10% improvement shown in EVITA represents “a nice impact,” he told TCTMD. “It’s a tough addiction, and so we should use every tool that we’ve got. In my mind, this is an excellent step forward. . . . As far as a pharmacologic therapy goes, this is as good as it gets.”

[Cardiologists] tend to punt this one to the primary care providers with the hope that the primary doc will just take care of it. And that doesn’t happen. Quinn R. Pack

EVITA enrolled 302 patients (mean age 55 years; 75.2% men) who were hospitalized for ACS, randomly assigning them to receive varenicline or placebo for 12 weeks. The median time from admission to first dose was 2 days, with a median hospital stay of 3 days. Most had presented with STEMI (56%), while 37.8% had NSTEMI and 6.3% had unstable angina. In addition to varenicline or placebo, patients received low-intensity counselling.

Smoking status was self-reported but validated using exhaled carbon monoxide. Overall, 34.4% did not smoke cigarettes at 52 weeks after their ACS, with varenicline users showing a higher quit rate than the placebo group (39.9% vs 29.1%). The 10.7% gap translated into a number needed to treat of 10. Patients in the varenicline arm also were more likely to report decreasing their daily cigarette smoking by 50% or greater (57.8% vs 49.7%), though that difference didn’t reach statistical significance.

Rates of serious adverse events and MACE were similar in the two groups.

Concerns raised 9 years ago by the US Food and Drug Administration (FDA) about varenicline and the potential for mental-health side effects were mostly dropped by the agency in 2016. Indeed, neither Eisenberg nor Pack expressed any worries about the drug in this regard, and both cited the EAGLES trial as reassuring. Currently, varenicline’s label advises keeping an eye out for neuropsychiatric adverse events like changes in mood or suicidal ideation, adding that patients should “discontinue Chantix and contact a healthcare provider if they experience such adverse events.”

Smoking Cessation as ‘Standard Practice’?

Varenicline “is the best agent we have out there” in terms of efficacy, surpassing nicotine patches, bupropion, and counseling alone, Eisenberg said.

Yet, as reported by Pack and his fellow investigators last year, fewer than one-quarter of smokers hospitalized for a cardiac event in the United States receive any form of pharmacotherapy to help them quit. “This is a major opportunity for cardiologists to change their practice,” Pack noted to TCTMD.

In an editorial accompanying the new CMAJ paper, Robert D. Reid, PhD, Kerri-Anne Mullen, PhD, and Andrew L. Pipe, MD (University of Ottawa Heart Institute, Canada), are similarly blunt: “Given the powerful effect of smoking cessation on subsequent cardiovascular morbidity and mortality, smoking cessation interventions including counseling and medications, initiated in the hospital and integrated into postdischarge support, should be standard practice for patients with acute coronary syndrome receiving treatment at hospitals in Canada.

“Anything less,” they say, “reflects substandard care.”

Pack even now isn’t confident that there will be a shift in practice. “Cardiologists are generally more interested in devices and procedures than they are in behaviors. They prescribe medicines pretty well, but most cardiologists (and there’s quite a lot of research that shows this) have never been adequately trained for smoking cessation,” he said.

Cardiologists often “haven’t ever prescribed varenicline in the past, or if they did, they did it just a few times. They don’t think about it,” Pack continued. “They tend to punt this one to the primary care providers with the hope that the primary doc will just take care of it. And that doesn’t happen. We know that there’s a sizeable performance gap there.”

Pack pointed out that, in EVITA, a large proportion of the placebo-group patients relapsed within 1 week. This provides a further argument that interventions must happen in the hospital, not 2 weeks later at a follow-up visit, he said.

Additionally, varenicline involves a “weeklong uptitration period, where the medication slowly uptitrates because there’s some nausea associated with it if you just start on a full dose,” Pack noted. During this time, it might be useful to “tide people over” with a combination approach while the efficacy of varenicline is building, “something to help ease the withdrawal and cravings, which tend to peak actually at around 1 to 2 weeks into cessation,” he suggested.

Eisenberg also observed “that it takes a while to have bioaccumulation.” In most settings, people start varenicline about a week before they try to quit. In the ACS population, a different tactic is needed, because patients aren’t allowed to smoke in the hospital. He agreed that giving these individuals a combination therapy, such as a nicotine patch on top of varenicline, during hospitalization might “take care of their symptoms while in-hospital and maybe increase quit rates after discharge.”

It also might be helpful to extend therapy beyond 12 weeks, Eisenberg suggested. “It’s a chronic condition, so to think that 12 weeks is going to reverse habit—these patients were smoking for 35 years on average—[is perhaps unrealistic]. It’s unlikely to turn it around.”