ORLANDO, Fla. — In the first clinical trial designed specifically for patients hospitalized for acute coronary syndrome (ACS), varenicline demonstrated efficacy for smoking cessation when initiated in hospital.

The findings were presented at the American Heart Association Scientific Sessions by Mark J. Eisenberg, MD, professor of medicine and director of Cardiovascular Health Services Research Program, Jewish General Hospital at McGill University in Montreal, Canada, and simultaneously published in Circulation.

The EVITA (Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome) trial assessed whether or not varenicline (Pfizer, New York, NY) treatment begun prior to hospital discharge would be effective in patients with ACS. More than 90% of the patients experienced myocardial infarction just before starting treatment. They also underwent interventional procedures such as cardiac catherization, percutaneous coronary intervention, or coronary artery bypass grafting.


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“This is the highest-risk population ever exposed to varenicline,” said Dr Eisenberg during his presentation.

Morbidity and mortality are substantially increased among patients who continue to smoke following ACS diagnosis, but less than one-third are able to remain abstinent, the researchers noted. Nicotine-replacement therapies (NRTs) are frequently prescribed in-hospital, but there have been no randomized clinical trials. NRTs include nicotine patches and gum, both of which have been studied in younger, healthier patients.

All patients (N=302) were hospitalized for ACS and received placebo or varenicline for 12 weeks. The average age was 55 years, approximately 75% were male, and two-thirds were randomized in Canada and one-third in the United States. At the time of the study, patients smoked a mean of 21 cigarettes per day and had been smoking a mean of 36 years. Treatment began 2 days after admission to the hospital with follow-ups via telephone and clinic.

The primary end point — point prevalence smoking abstinence, as defined by self-report of complete abstinence in the 7 days prior to the 24-week visit and confirmed by a measured exhaled carbon monoxide ≤10 ppm — was met in 47.3% of patients who received varenicline compared with 32.5% who received placebo (P=.0012). The abstinence rate in the treatment group was even higher than in the placebo group at 4 weeks (60% vs 37.7%; P<.001) and at 12 weeks (57.7% vs 36.4%; P<.001). At 24 weeks, point prevalence abstinence rates were 47.3%  in the varenicline group vs 32.5% in the placebo group (P=.012) for a number needed to treat (NNT) of 6.8.

Continuous smoking abstinence (defined as not having 1 puff of a cigarette during the entire follow-up period and exhaled carbon monoxide ≤10 ppm) was evaluated as a secondary end point. The researchers noted, “Continuous abstinence is a very rigorous end point which does not allow for any ‘slips.’” The varenicline group had a continuous abstinence rate of 35.8% compared with 25.8% in the placebo group (P=.081; NNT=10.0).

The researchers also evaluated rates of reduction ≥50% in cigarette in daily cigarette consumption. At 24 weeks, this rate was 67.4% with varenicline vs 55.6% for placebo (P<.05; NNT=8.5).

While the study was not powered to evaluate safety end points, the researchers noted that within 30 days of discontinuation of the study drug, serious adverse events occurred in 11.9% of the varenicline group and 11.3% of the placebo group, and major adverse cardiovascular events occurred in 4.0% of the varenicline group and 4.6% of the placebo group.

Two deaths also occurred within 30 days of drug discontinuation in the varcenicline group and 1 occurred after 30 days. Two were cardiovascular-related (congestive heart failure and sudden death) and 1 resulted from a perforated ulcer.

In terms of other adverse events, 1 patient developed depression 25 days after taking 1 dose of varenicline and was hospitalized, and approximately 15% of the treatment group reported abnormal dreams.

A 12-month follow-up of this study will conclude in December 2015 and results should be available in early 2016.

Disclosures: Dr Eisenberg received honoraria from Pfizer Inc for providing continuing medical education on smoking cessation.

References

1. Eisenberg M. LBCT.02 – Decreasing the Global Burden of Disease: Breakthroughs in Prevention. The Efficacy and Safety of Varenicline, a Selective Alpha4beta2 Nicotinic Receptor Partial Agonist, for Smoking Cessation in Patients Hospitalized With Acute Coronary Syndrome: A Randomized Controlled Trial. Presented at the American Heart Association Scientific Sessions. November 7-11, 2015; Orlando, FL.

2. Eisenberg M, Windle SB, Roy N, et al; for the EVITA Investigators. Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome. Circulation. 2016; 133:00-00. DOI: 10.1161/CIRCULATIONAHA.115.019634.