Varenicline Safe for Smoking Cessation, Reduces Hospitalization Risk

Greg Carney, PhD

Varenicline, an effective medication for smoking cessation, was not associated with an increased risk of cardiovascular or neuropsychiatric hospitalizations compared with nicotine replacement therapy, according to new study findings.

Bupropion, a smoking cessation aid and antidepressant, was linked with lower risks of cardiovascular hospitalizations and higher risks of neuropsychiatric hospitalizations compared with nicotine replacement therapy.

The findings suggested that varenicline should continue to be considered as a treatment option for smoking cessation.

Greg Carney, PhD, and a team of investigators designed a retrospective new-user cohort study to analyze 2 alternatives to nicotine replacement therapy, varenicline and bupropion, to learn associated hospitalizations.

Carney, a research program manager in the anesthesiology, pharmacology, and therapeutics department at University of British Columbia in Canada, and colleagues used US administrative data from 2006-2016 covering >100 million individuals. Data came from the Truven Health MarketScan Research Database of insurance claims from employers, health plans, and state Medicaid agencies. Data included deidentified and linkable patient claims for outpatient prescription medications, physician outpatient visits and services, and hospital discharge records.

Patients in the study were >18 years old who used varenicline, bupropion 150 mg sustained release, or any form of nicotine replacement therapy. Exclusion criteria included if a patient did not have >12 months of continuous health insurance; being <18 years old; using >1 smoking cessation product; having a prior prescription for any smoking cessation pharmacotherapy in the previous 12 months; and being diagnosed or treated for depression in the 12 months before the index date.

The primary measure of the study was a composite of hospitalized cardiovascular events, while secondary outcomes included a composite of hospitalized neuropsychiatric events and individual aspects of the primary measure.

Nearly 618,500 patients met inclusion criteria. Among them, 454,698 used varenicline, 131,562 used bupropion, and 32,237 used nicotine replacement therapy. Patients were an average of 46 years old, and nicotine replacement therapy users were an average 3.5 years older than bupropion users and 3.6 years older than varenicline patients.

Women made up 61% of the bupropion group (79,662) compared with 44% (199,376) and 46% (14,827) of the varenicline and nicotine replacement therapy cohorts.

At baseline, patients who used nicotine replacement therapy had higher rates of alcohol abuse; chronic obstructive pulmonary disease; diabetes; chronic kidney disease; and history of cardiovascular disease than those who took varenicline or bupropion.

During a one-year follow-up period, varenicline was associated with a 20% one-year relative risk reduction of cardiovascular event hospitalizations compared to nicotine replacement therapy (RR, .8; 95% CI, .75-.85). Bupropion was associated with a 25% one-year relative risk reduction compared to such therapy (RR, .75; 95% CI, .69-.81).

Varenicline, compared with nicotine replacement therapy, was also associated with a one-year relative risk reduction for 5 outcomes: cerebral infarction (RR, .71; 95% CI, .6-.84); hospitalization for heart failure (RR, .72; 95% CI, .65-.81); hospitalization for peripheral vascular disease (RR, .83; 95% CI, .75-.92); ischemic heart disease (RR, .92; 95% CI, .82-1.03); and angina (RR, .9; 95% CI, .72-1.13). There was an increase in risk for coronary revascularization (RR, 1.07; 95% CI, .77-1.47).

The medication was associated with a 35% reduction in one-year relative risk of hospitalization for neuropsychiatric events (RR, .69; 95% CI, .59-.72).

Compared with nicotine replacement therapy, bupropion was linked to lower one-year relative risks of hospitalization for ischemic heart disease (RR, .79, 95% CI; .69—.91); cerebral infarction (RR,.78; 95% CI, .64–.96); heart failure (RR, .84; 95% CI, .74–.96); and peripheral vascular disease (RR, .65; 95% CI, .57–.74). In addition, there were lower reductions for coronary vascularization (RR, .68; 95% CI, .44–1.03) and angina (RR, .80; 95% CI, .59– 1.07).

Bupropion was associated with a 21% increase in one-year relative risk of hospitalization for neuropsychiatric events compared to nicotine replacement therapy (RR, 1.21; 95% CI, 1.09-1.35).

In a comparison between bupropion versus varenicline, there was a 17% reduction in one-year relative risk of cardiovascular event hospitalization (RR, .83; 95% CI, .78-.97) and a 77% increase in one-year hospitalization for neuropsychiatric events (RR, 1.77; 95% CI, 1.66-1.88).

The findings of the study addressed the need for evidence of the safety of varenicline and bupropion compared to nicotine replacement therapy. The results added support to the US Food and Drug Administration’s decision to remove the varenicline Boxed Warning for neuropsychiatric events.

“We hope that our study’s findings will promote a better understanding of these medications for quitting smoking,” Carney said in a statement.

The study, “Cardiovascular and neuropsychiatric safety of smoking cessation pharmacotherapies in non-depressed adults: a retrospective cohort study,” was published online in the journal Addiction.