Smoking-cessation therapy efficacious when initiated in hospital following ACS

ORLANDO, Fla. — Treatment with the smoking-cessation agent varenicline initiated in the hospital after ACS, in conjunction with low-intensity counseling, increased smoking abstinence compared with placebo.

The randomized, placebo-controlled, double blind EVITA trial evaluated the efficacy of varenicline (Chantix, Pfizer) in 302 patients hospitalized with ACS (56% STEMI, 38% non-STEMI, 6% stable angina) in the United States and Canada. Close to 100% of patients had cardiac catheterization during the index hospitalization. The patients’ mean age was 55 years; 75% were men.

The study enrolled adults who reported smoking for more than 3 decades but who were motivated to quit, Eisenberg, professor of medicine and director of the cardiovascular health services research program at Jewish General Hospital and McGill University in Montreal, Canada, said during a press conference. At the time of ACS, the patients reported smoking about a pack a day (mean, 22 cigarettes).

Mark J. Eisenberg, MD, of Jewish General Hospital/McGill University, Montreal, Quebec, Canada, and colleagues randomly assigned patients to 12 weeks of twice-daily varenicline 1 mg or matching placebo, on top of low-intensity counseling on smoking cessation. Follow-up by telephone occurred at weeks 1, 2 and 8 and clinical visits occurred at weeks 4, 12 and 24.

“This is the highest-risk patient population that has been exposed to varenicline,” Eisenberg said.

At 24 weeks, the primary endpoint of point-prevalence smoking abstinence was 47.3% in the varenicline group vs. 32.5% in the placebo group (P = .012; number needed to treat, 6.8). Point-prevalence smoking abstinence was assessed by 7-day recall and biochemical validation using expired carbon monoxide, Eisenberg said during a press conference.

In other results, the rate of continuous abstinence was 35.8% in the varenicline group vs. 25.8% in the placebo group (P = .081; number needed to treat, 10) and the rate of reduction ≥50% in daily cigarette consumption was 67.4% vs. 55.6%, respectively (P = .05; number needed to treat, 8.5).

Serious adverse events occurred in 11.9% of the varenicline group vs. 11.3% of the placebo group (P > .99) and major adverse CV events occurred in 4% vs. 4.6%, respectively. The most common side effects at 12 weeks were insomnia (varenicline, 17.9% vs. placebo, 12.6%; P = .26), nausea (13.9% vs. 8.6%, respectively; P = .2) and abnormal dreams (15.2% vs. 4.6%, respectively; P < .01). Seizure or suicidal ideation was not reported, but one patient had a neuropsychiatric event classified as “other.” Three deaths occurred in the varenicline group; one death was attributable to congestive HF, the second to sudden death and the third to a perforated ulcer.

Eisenberg noted that the EVITA study was “not powered to look at safety endpoints.”

“Future studies are needed to establish safety in these patients,” he said.

Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist. The therapy reduces cravings and symptoms of withdrawal during smoking abstinence.

“These findings suggest that smoking remains a persistent problem in patients experiencing ACS and that varenicline is an efficacious pharmacotherapy for smoking cessation in these patients,” the researchers wrote in the simultaneous publication in Circulation. “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 [Wellbutrin, GlaxoSmithKline] in these patients suggest that it is not efficacious.” – by Katie Kalvaitis

References:

Eisenberg MJ, et al. Late-Breaking Clinical Trials 2. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.

Eisenberg MJ, et al. Circulation. 2015;doi:10.1161/CIRCULATIONAHA.115.019634.

Disclosure: Eisenberg reports receiving honoraria from Pfizer for providing continuing medical education on smoking cessation.