Just 3.2% of adult smokers with peripheral artery disease (PAD) were prescribed the smoking-cessation drug varenicline, according to a new study.

Smoking is the leading modifiable risk factor associated with progression of PAD, and varenicline has the greatest efficacy among available cessation medications, the authors wrote. 

The medication tends to be underutilized, said lead author Ken R. Cohen, MD, but its minimal use among patients with PAD was surprising.

“I expected the rate to be on the low side, but not 3%,” Cohen, who is chief medical officer and executive director of Health Outcomes Research at Optum Health in Eden Prairie, Minnesota, told Medscape Medical News. “That’s dismally low.”

Few Prescriptions Filled

PAD, caused by atherosclerotic obstructions in the limbs, affects 8.5 million people in the US and more than 235 million globally. Smoking is linked to a threefold to fourfold greater risk of developing PAD and a higher chance of disease progression, postsurgical outcomes, and limb ischemia, while quitting smoking improves clinical outcomes.

The cross-sectional study analyzed medical and pharmacy claims from 135,156 de-identified individuals obtained from the OptumLabs Data Warehouse and enrollment records for commercial health insurance and Medicare Advantage plans.

The group included adults (54.4% men) with symptomatic PAD based on at least one medical claim for intermittent claudication between July 1, 2016, and December 31, 2022. Eligible participants were insured for at least 6 months prior to the claim and a 12-month washout period ensured that none had prior intermittent claudication diagnoses.

Among the participants, 107,065 (79.2%) were smokers according to diagnosis or procedure codes in their electronic health records, and 3394 (3.2%) filled at least one prescription for varenicline after their claudication diagnosis.

Varenicline use was higher in those aged 65 years or younger than those older than 65 years (43.1% vs 18.6%) and commercially insured patients vs Medicare enrollees (4.2% vs 3.0%).

The results were published in a research letter online on February 23 in JAMA Open Network.

Lingering Concerns?

The authors acknowledged their results probably underestimated the use of varenicline.

Timothy B. Baker, PhD, associate director and director of Research at the Center for Tobacco Research and Intervention at the University of Wisconsin-Madison, told Medscape Medical News that physicians may be reluctant to prescribe varenicline due to lingering concerns about its safety and unpleasant side effects, which included suicidal ideation and other neuropsychiatric effects.

Pfizer released the drug under the brand name Chantix in 2006 and took it off the market in 2021 after the detection of nitrosamine contamination. Varenicline has been available only in generic form since that year. The loss of Pfizer’s product cut into the supply tremendously and it took a long time to come back, Baker said, but “it’s quite safe now and should be used.”

The study didn’t examine information not contained in the claims or electronic health record data such as socioeconomic factors, smoking intensity, or use of nonprescription cessation methods like quitlines or counseling. The research is part of a larger trial, currently under review, examining whether medical treatments or vascular interventions result in better outcomes in patients with newly symptomatic PAD.

Smoking Assessment Should Be ‘Routine’

“These findings suggest barriers at both clinician and patient levels,” the authors wrote.

By the point of PAD diagnosis, patients may have tried quitting tobacco multiple times and may be on the verge of giving up; that’s a critical moment to counsel them to quit and prescribe varenicline to help, Cohen said.

But he and Baker agreed the realities of modern medical care — time pressures, focusing on immediate care instead of long-term health goals, and diffusion of responsibility in which the smoking discussion is lost — often discourage successful quitting.

In an invited commentary also published online on February 23 in JAMA Open Network, Baker wrote that past attempts to treat smoking in the context of cancer, severe mental illness, and pulmonary disorders “[suggest] that exhorting clinicians to do more will not work.” Instead, he argued for changes in electronic health record systems that “routinize” assessment of smoking status of patients with PAD and make it easier to link them to quitlines or specialists.

The National Cancer Institute’s Cancer Center Cessation Initiative provides a successful model, Baker said. Beginning in 2017, 52 cancer centers shared insights to develop and implement evidence-based tobacco cessation programs for adults with cancer. More than 100,000 patients received cessation treatment between 2018 and 2022. The knowledge gained from the initiative is available for adaptation in other disease contexts.

While busy physicians may not always have the time for a lengthy consultation, Cohen said, data show that 1 minute of counseling can engage a patient to quit smoking.

“A message like ‘It’s the single most important thing they can do’ may be enough,” Cohen said.

Study co-authors Jarvis, Catlett, and Sullivan reported owning stock in United Health Group. No other disclosures were reported. Commentary authors Baker, Fiore, and Stein reported receiving grants from the National Institutes of Health during the conduct of the study.

Kat Long is a science journalist in the Washington, DC, area.