Major and minor complications greater among smokers

A review of data from more than 14,000 intermittent claudication (IC) patients treated at Pittsburgh’s VA Healthcare System offered stark confirmation of what has long been known: smoking dramatically increases the risk of peripheral arterial disease (PAD), and smokers are likely to have serious—sometimes fatal—complications following procedures to treat IC.

Among more than 7,000 propensity-matched cases drawn from 14,350 cases reviewed, smokers had a greater risk for every type of complication—respiratory, wound, graft failure—within the 30 days following procedures, and that increased risk was observed for endovascular revascularizations, hybrid revascularization, and open revascularization, wrote Edith Tzeng, MD, of the division of vascular medicine at the University of Pittsburgh School of Medicine and Veterans Affairs Pittsburgh Healthcare System and colleagues in JAMA Cardiology.

“A total of 1,594 patients (11.1%) had complications, and 57 (0.4%) died. Among 7,710 propensity score–matched cases (including 3,855 smokers and 3,855 nonsmokers), 484 smokers (12.6%) and 34 nonsmokers (8.9%) experienced complications, an absolute risk difference (ARD) of 3.68% (95% CI, 2.31-5.06; P<0.001),” Tzeng et al wrote. “Compared with nonsmokers, any complication was higher for smokers following endovascular revascularization (26 [4.3%] versus 52 [2.1%]; ARD, 2.19%; 95% CI, 0.77-3.60; P=.003), hybrid revascularization (204 [17.3%] versus 163 [14.1%]; ARD, 3.18%; 95% CI, 0.23-6.13; P=.04), and open revascularization (228 [15.4%] versus 153 [10.3%]; ARD, 5.18%; 95% CI, 2.78-7.58; P<.001).”

The risk of complications was greatest among smokers who were “non-White Hispanic patients and those with COPD and nonfrail status compared with non-White Hispanic patients and those without COPD and frailty.”

In an editorial, Mark A. Creager, MD, of Dartmouth-Hitchcock’s Heart and Vascular Center in Lebanon, New Hampshire, and Naomi M. Hamburg, MD, of the Whitaker Cardiovascular Institute at Boston University School of Medicine, pointed out that cigarette smoking carries a greater risk for PAD than for CAD, with an attributable risk that exceeds 40%.

“Yet among patients with PAD, the percentage of active smokers likely exceeds 30%, and in the Veterans Affairs study reported by Reitz and colleagues, it exceeded 50%. Therefore, smoking cessation programs targeting patients with PAD are needed. Smoking cessation substantially reduces the incidence of PAD and PAD hospitalizations, although elevated risk persists even among former smokers,” Creager and Hamburg write. “Importantly, patients with PAD who quit smoking have decreased mortality and increased amputation-free survival compared with those who continue to smoke. Yet relatively few patients with PAD who smoke are referred for smoking cessation counseling or prescribed pharmacologic treatment, despite evidence supporting the efficacy of these interventions.”

BreakingMED asked Creager if he knew of any VA standard protocals for smoking cessation among IC patients.

“There is no systematic requirement for smoking cessation prior to revascularization for claudication Rx at the VA,” Creager wrote in an email reply. He added that, to his knowledge, “there is also no such requirement prior to approval for invasive treatment for intermittent claudication by CMS.”

Are there data demonstrating increased PAD risk with products such as electronic cigarettes and vape products, or are those products too new to market for such data to mature?

There is no current data that we are aware of about electronic cigarettes and PAD. We are awaiting more studies to address this question, and specifically what the vascular health effects are of transitions between tobacco products

The Pittsburgh researchers used “nearest-neighbor (1:1) propensity score matching 2011 to 2019 data from the Veterans Affairs Surgical Quality Improvement Program. Most of the patients (98.2%) were men and the median age was 65.7. More than half (54.5%) were smoking within the preprocedural year.

In the propensity-matched cohort, major severe complications were more common among smokers (n=255, 6.6%) versus nonsmokers (n=195, 5.0%)—ARD 1.56 (95% CI 0.51-2.60; P=0.004); matched OR 1.33 (95% CI 1.10-1.61; P< 0.001); and adjusted OR 1.21 (95% CI 0.03-1.13; P=0.02). Minor complications were also more common among smokers (n=265, 6.9%) versus nonsmokers (n=163, 4.2%)—ARD 2.65 (95% CI 163-3.67; P <0.001); matched OR 1.67 (95% CI 1.37-2.04; P<0.001); and adjusted OR 1.5 (95% CI 1.27-1.81; P<0.001).

“Compared with nonsmokers, respiratory complications were higher for smokers following endovascular revascularization (20 [1.7%] versus 6 [0.5%]; ARD, 1.17%; 95% CI, 0.35-2.00; P=.009), hybrid revascularization (33 [2.8%] versus 10 [0.9%]; ARD, 1.93%; 95% CI, 0.85-3.02; P=.001), and open revascularization (32 [2.2%] versus 19 [1.3%]; ARD, 0.89%; 95% CI, 0-1.80; P=0.06). However, wound and thrombotic complications were only significantly higher for smokers compared with nonsmokers undergoing open procedures (wound: 146 [9.9%] versus 87 [5.8%]; ARD, 4.05%; 95% CI, 2.12-5.99; P<.001; thrombotic: 41 [2.8%] versus 16 [1.1%]; ARD, 1.71%; 95% CI, 0.72-2.69; P=.001),” Tzeng and colleagues wrote. “Notably, the risk of vascular graft failure was also significantly higher for smokers compared with nonsmokers undergoing open revascularization (33 [2.2%] versus 11 [0.7%]; ARD, 1.50%; 95% CI, 0.63-2.37; P=.001). Smoking was associated with increased 30-day mortality (23 [0.6%] versus 2 [0.1%]; ARD, 0.54%; 95% CI, 0.29-0.80).”

Tzeng and colleagues noted that although all smokers—even those with less severe disease—had increased risks for complications, that risk “fell by 29% for former smokers (n=4,755; adjusted odds ratio 0.71; 95% CI 0.61-0.83; P=.001)” with more than 1 year of smoking cessation and by 65% among never smokers (adjusted odds ratio, 0.45; 95% CI, 0.34-0.59).

In addition to being a retrospective study, the findings from Tzeng et al are limited by the fact that the data were extrapolated from billing information and medical records and thus have a risk of measurement error. Also, the sample was predominately male, data did not include annual incidence of IC procedures, and most importantly the data “could not discern if smoking cessation was part of PAD-related [optimum medical therapy]…”

The editorialists point out that smoking is a modifiable risk factor that must be addressed, and they make the case that pharmacologic intervention combined with behavioral therapy is the optimal approach for smoking cessation, according to the editorialists.”

“At each patient interaction, the importance of smoking cessation should be discussed using the AAC framework (Ask-Advise-Connect): (1) ask about smoking status, including all types of tobacco products (combustible cigarettes, electronic cigarettes, vape products, hookah, cigar products, and smokeless tobacco); (2) advise about the impact of smoking cessation on health status in a personalized manner; and (3) connect with referral to a formal smoking cessation program and prescriptions for medical therapies and follow-up,” they wrote,

Asked to clarify PAD risk with e-cigarettes or vape products, Creager acknowleged that there are “no current data that we are aware of about electronic cigarettes and PAD. We are awaiting more studies to address this question, and specifically what the vascular health effects are of transitions between tobacco products.”

Take advantage of the statewide quitlines in addition to health care system resources. The connection between smoking and procedural outcomes provides an opportunity to craft messaging that cessation therapies are part of the treatment plan to treat their intermittent claudication. Available pharmacologic options include nicotine replacement therapy, buproprion, and varenicline. Dual nicotine replacement with patch combined with either gum or lozenges is more effective than a single nicotine replacement product alone, as it delivers basal and bolus dosing. Varenicline has the greatest efficacy and has been shown to have no neuropsychiatric adverse effects compared with placebo,” Creager and Hamburg advised.

  1. In a cohort study of patients with intermittent claudication, smoking within a year of revascularization treatment was associated with a 48% increase in risk of early postprocedural complication.

  2. Former smokers (more than 1 year cessation) had a 29% lower risk of complications compared to current smokers, and the risk was 65% less for never smokers.

Peggy Peck, Editor-in-Chief, BreakingMED™

Tzeng and co-authors had no financial disclosure.

Creager is supported by a Strategically Focused Vascular Disease Research Network grant from the American Heart Association. Hamburg has consulted for Merck, Bayer, NovoNordisk, and Sanifit; has equity interest in Acceleron Pharma; and is supported by grants from the American Heart Association and the National Heart, Lung, and Blood Institute.

Cat ID: 206

Topic ID: 74,206,730,206,308,192,925,159