Smoking-Cessation Drug Bupropion Not Effective in the Post-AMI Setting

January 29, 2013

MONTREAL, Quebec City— Treatment with bupropion failed to halt cigarette smoking in patients hospitalized with acute MI, as more than two-thirds of these patients returned to smoking by 12 months after their AMI [1]. Although safe and well tolerated in the immediate post-AMI period, investigators conclude that the smoking-cessation drug is not effective in patients who had an AMI.

Dr Mark Eisenberg (McGill University, Montreal, QC), the lead investigator of the Zyban as an Effective Smoking Cessation Aid for Patients following an Acute Coronary Syndrome (ZESCA) study, which is published in the February 5, 2013 issue of the Journal of the American College of Cardiology, told heartwire he was disappointed in the findings, given the massive public-health benefits of getting these patients to stop smoking.

"When we originally conceived the trial, I was initially looking for a magic bullet that would cure smoking in patients who are smokers who come in with MIs," he said. "We're very effective in the [cardiac care unit] CCU dealing with patients with MI. Everybody gets aspirin, clopidogrel, a statin, beta-blockers, and ACE inhibitors. I thought if we had one more magic pill that we could give while the patients were admitted with MI, and this could get them to stop smoking, this would have had a tremendous public-health benefit."

Speaking with heartwire , Eisenberg said that a patient with MI who continues to smoke has more than double the risk of recurrent MI or death compared with a patient who stops smoking. With several effective agents available to help with smoking cessation, including nicotine-replacement therapy, the researchers were hopeful that the study would be positive but weren't surprised, given the difficulties in getting smokers, most of whom smoked for more than three decades or more, to quit.

The ZESCA Study

The ZESCA study was a multicenter, double-blind, placebo-controlled, randomized clinical trial in 392 patients hospitalized with AMI. All patients received bupropion of placebo for nine weeks and were followed for 12 months.

At one year, 37.2% of patients in the bupropion treatment arm had stopped smoking while 32.0% in the placebo arm had also quit, a nonsignificant difference. Eisenberg said the study might even overestimate the number of patients who quit smoking post-MI, as ZESCA enrolled motivated individuals with a desire to stop. There was a reduction in the number of cigarettes smoked, down from 23/day at baseline to 8.4/day at 12 months.

The trial enrolled just 20% of their expected target because patients were frequently adamant they would quit on their own or were not interested in quitting. Eisenberg told heartwire that while a cardiovascular event might be a "teachable moment" for the patient and their family, having an AMI is not the same today as it was 30 years ago. "Now they're in the hospital for a couple of days, they have an angioplasty, and then they're back on the golf course," he said.

In the ZESCA study, counseling involved what would typically occur in the AMI population, that being a brief two-minute counseling session with the cardiologist. Further interactions with research nurses involved approximately five minutes of counseling. This occurred in the hospital and with telephone conversations to assess for side effects. On average, patients received about 40 minutes of counseling in both the treatment and placebo arms.

"Critics may say that we would have had a much better result if we had high-intensity counseling, but that is often logistically difficult to deliver in most MI patients," said Eisenberg. "We were trying to replicate what typically goes on and to see if the addition of a medication known to be an effective smoking-cessation agent would be enough to do it. But that did not appear to be the case."

The researchers are currently conducting a similar study known as the Evaluation of Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome (EVITA) trial.Eisenberg noted that head-to-head studies of varenicline (Champix/Chantix, Pfizer) and bupropion have suggested varenicline is more effective in getting patients to quit smoking, leaving them optimistic the next study might be positive. However, they are encountering similar issues in that many patients, smokers for more than 30 years, are insisting on going "cold turkey" or who feel hopeless that they can quit.

Achieving Success in This High-Risk Population

In an editorial accompanying the study [2], Dr Neil Benowitz (University of California, San Francisco) and Dr Judith Prochaska (Stanford University, CA) write that hospitalization for an acute cardiovascular event provides an opportunity for patients to quit smoking because patients are likely highly motivated to quit and have to at least temporarily stop while hospitalized.

That said, their level of dependence is often quite high, with many patients smoking for years despite having several cardiovascular risk factors, and the duration of their hospital stay is often brief. In addition, some physicians might be reluctant to prescribe a smoking-cessation drug in the post-AMI setting because patients are already prescribed a number of cardiovascular medications, as well as other medications for comorbid conditions. Regardless, physicians need to actively engage their patients to help them quit smoking.

"In conclusion, the standard of care for managing patients after myocardial infarction should include not only blood pressure and lipid management but also smoking cessation," write Benowitz and Prochaska. "At present, the quit rates for smokers after myocardial infarction are higher than those for the general population of smokers, yet given the enormous health risks, still much too low."

Recommendations for Smoking Cessation in Hospital

The editorialists recommend that the following be implemented in the hospital to assist with smoking cessation in the high-risk AMI population:

Effective counseling in the hospital for all smokers--"Hospital-based cessation treatment needs to be proactive, tailored to readiness to quit, progressive in the use of nicotine replacement for the management of withdrawal symptoms, and focused on gaining buy-in and building rapport for continued treatment and patient adherence posthospitalization," they write.

Effective transition from inpatient to outpatient smoking-cessation treatment (minimum one-month follow-up).

Prescription of medication to manage withdrawal and support long-term cessation.

Management of comorbid mental health issues, including depression, which can be triggers for smoking relapse.

These recommendations, they point out, are in line with the Joint Commission's current recommended hospitalwide standards.

The study was funded by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Quebec. Eisenberg received funding from Pfizer Canada, to perform the EVITA trial. Disclosures for the coauthors are listed in the paper.