EVITA: Varenicline Started in ACS Hospitalization Can Help Smokers Quit

November 09, 2015

ORLANDO, FL ( UPDATED WITH COMMENTARY ) — The smoking-cessation drug varenicline (Chantix/Champix, Pfizer), which has been shown to work in patients with stable coronary disease, can also help those hospitalized with acute coronary syndromes to kick the habit, according to researchers based on their randomized, controlled trial[1].

In the Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome (EVITA) trial, patients who were smokers and who started on varenicline while hospitalized for ACS were significantly more likely than a control group to be smoking-abstinent 24 weeks later. The smoking-cessation intervention also included "low-intensity counseling," a mean of 46 minutes total for the entire trial.

"Our results are important because clinical trials have not examined the efficacy of nicotine-replacement therapy in this patient population and because several trials of bupropion in these patients suggest that it is not efficacious," observe Dr Mark J Eisenberg, Jewish General Hospital/McGill University, Montreal, QC) and colleagues. Their report is published today in Circulation to coincide with Eisenberg's scheduled EVITA presentation here at the American Heart Association (AHA) 2015 Scientific Sessions.

Success in a Challenging Patient Population

"Without smoking-cessation therapy, less than a third of smokers hospitalized with acute coronary syndrome remain abstinent after discharge," Eisenberg said for heartwire from Medscape. "And in fact, the numbers that I'm presenting today are probably much better than they are in real life, because many patients are not motivated to quit—not even willing to take medication for smoking cessation."

EVITA is, he said, "I think, the first trial with a clinical therapy started in the hospital that looks like it's effective for smoking cessation in ACS patients."

Dr David A Wood (National Heart & Lung Institute, Imperial College London, UK), who isn't an EVITA investigator, sees an opportunity in the predischarge setting to double-down on smoking-cessation medications. "Patients with ACS stop smoking, for the most part, obviously, in the hospital. And so the question is, can you prevent them from relapsing once they leave?" he said to heartwire .

"Managing withdrawal with nicotine-replacement therapy in-hospital in the context of ACS is extremely important in addition to, based on this trial, starting varenicline to prevent relapse," according to Wood.

"Varenicline will reduce the craving for cigarettes, but the impact is not immediate. Using nicotine-replacement therapy will immediately affect that craving. So the combination of the two may be very powerful."

ACS hospitalization is a special opportunity in other ways for getting patients off cigarettes in that it represents a powerful "teachable moment," emphasized Dr Donald Lloyd-Jones (Northwestern University Feinberg School of Medicine, Chicago, IL), also not with EVITA. The trial, he told heartwire , produced "very good results," but there were just 12 weeks of therapy, "so it does require follow-up if we want to sustain it."

Eisenberg acknowledged that the difference in smoking-abstinence rates between the two groups in the trial attenuated a bit between 12 and 24 weeks, but "it's normal in all smoking-cessation trials that there's a tapering off as we go."

That underscores the importance of continued late follow-up and taking further action as needed. "You see somebody at 1 year post-MI who's still smoking, maybe it's time to go after them again, perhaps with another medication of smoking-cessation and behavioral therapy."

Breath Test Confirmed Smoking Cessation

EVITA's 302 smokers ACS in the US and Canada were randomized to start on varenicline or placebo in-hospital and to continue them for 12 weeks. Entry required them to have smoked at least 10 cigarettes a day (the mean was 21 per day, and they averaged 36 years of smoking).

Dr Mark J Eisenberg

The group's mean hospitalization time was 3 days; 56% had been hospitalized with ST-segment-elevation MI (STEMI), 38% with non-STEMI, and 6% with unstable angina; 98% underwent cardiac catheterization, 84% had PCI, and 6% went to CABG.

Varenicline was given at 0.5 mg in one daily dose for 3 days, followed by 0.5 mg twice a day for 4 days, followed by 1.0 mg twice a day for the rest of 12-week treatment period (the study continued with follow-up out to week 24).

Patients were evaluated for "point prevalence smoking abstinence" at 24 weeks, the primary end point, determined by the patients' own report of complete abstinence during the previous 7 days of follow-up and confirmed by measurements of exhaled carbon monoxide. Regardless of what a patient reported, exhaled carbon monoxide >10 ppm indicated smoking in the previous week for the purposes of the study. Continuous abstinence meant the patient attended all follow-up visits and each time self-reported abstinence and tested negative for the carbon monoxide finding.

End Points at 24 Weeks in EVITA, Varenicline vs Placebo

End points Varenicline Placebo P NNT
Primary end point (%) 47.3 32.5 0.012 6.8
Continuous abstinence (%) 35.8 25.8 0.081 10.0
≥50% reduction in daily cigarettes 67.4 55.6 0.05 8.5

Rates of adverse events within a month of going off the randomized agent were not statistically different between the actively treated and placebo groups; the serious adverse-event rates (usually death or recurrent ACS) were 11.9% and 11.3%, respectively, and major adverse CV event rates were 4.0% and 4.6%, respectively.

Side effects, especially insomnia and nausea, were common in both groups, according to the authors. The only observed significant difference in side effects, with a higher rate in actively treated patients, was for "abnormal dreams," 15.2% vs 4.6% (P<0.01).

Discontinuation of randomized agent due to adverse events occurred at similar rates, 11.3% for the varenicline group and 12.8% for controls.

EVITA wasn't powered for safety end points, according to Eisenberg and colleagues; on the other hand, "the patient population enrolled in the trial was the highest-risk patient population treated with varenicline to date," they write.

"Over 90% of the patients enrolled in EVITA had a myocardial infarction within the few days preceding their first dose of study medication. If varenicline is associated with an increase in adverse cardiovascular events, one would expect to see a signal to that effect among the EVITA patient population."

The investigator-initiated trial was funded by Pfizer, from which Eisenberg discloses receiving honoraria. The report's coauthors report no relevant financial relationships, nor did Wood and Lloyd-Jones.

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