Impact of Diabetes on Outcomes of Patients With Lower Extremity Artery Disease

During recent years, several observational studies used large administrative or clinical registries to emphasize the outcomes of patients who were treated for symptomatic lower extremity artery disease (LEAD). Between 13–50% of the patients with intermittent claudication (IC) and 50–90% with chronic limb-threatening ischemia (CLTI) will be amputated or even dead after 5 years.^1,2 In clinical cohorts, the prevalence of concomitant diabetes in patients treated for LEAD reached up to 50% and there is an interrelationship between concomitant diabetes mellitus and peripheral arterial disease. ³ Besides atherosclerotic plaques as common cause of LEAD, more recent data shows the additional role of non-atherosclerotic medial arterial calcification in patients with diabetes. ⁴ The possible impact of diabetes on LEAD symptoms, treatment decision, and outcomes may be crucial.

Lapébie and colleagues retrospectively used the Cohorte de Patients Artériopathes (COPART) registry comprising 2494 patients (49.5% with diabetes) to compare the prognosis during a 1-year follow-up after hospitalization for LEAD by diabetes status. ⁵ In adjusted multivariate analyses, diabetes was associated with major adverse cardiovascular events (MACE) and all-cause mortality after approximately 280 days, but not with major amputation. A meta-analysis including 31 studies with 58 113 patients recently compared the outcomes after LEAD treatment in diabetic patients with those without diabetes. ⁶ For a mean follow-up duration ranging from 1 to 89 months, diabetes was significantly associated with long-term mortality (relative risk (RR) = 1.67; 95% confidence interval (CI), 1.43–1.94; P < .001). ⁶ Diabetes was also significantly associated with lower primary and secondary patency.

The interesting study by Lapébie and colleagues underlines once again that the prevalence of diabetes among patients with LEAD is considerably high. ⁵ Although, diabetes prevalence in France is slightly lower than the mean prevalence among whole population aged 20–79 years in Europe (8.6 vs 9.2%, 2021), ⁷ almost half of the cohort were diabetics. It is notable that 250 patients were lost to follow-up before 365 days, emphasizing the challenge to collect complete longitudinal data in clinical cohorts.

Interestingly, the authors further discussed the obvious differences between clinical cohorts derived from either administrative data vs registries. Against that backdrop, the wide variation between databases concerning the proportion of women, patients with claudication, and endovascular procedures recently gained increasing interest. ⁸ It appears important to continue these efforts and collect real-world data to bring together the pieces in the puzzle. Furthermore, the strikingly high prevalence of diabetes may have manifold implications for both clinical practice and health services research. To name but a few, while many studies have adjusted their analyses for differences in optimal pharmacological treatment (e.g., statins, antiplatelets, and antihypertensives), the potential role of sodium-glucose co-transporter 2 (SGLT2) inhibitors in these patients remains uncertain. Initiated by an ongoing controversy concerning evidence for excess amputation rates from the Canagliflozin Cardiovascular Assessment Study (CANVAS) program, a large real-world study most recently found that SGLT2 inhibitors may improve heart failure outcomes in patients with both LEAD and diabetes. ⁹ In light of the wide variation and increasing evidence suggesting that patients with LEAD are underprivileged in terms of optimal pharmacological treatment, it might be reasonable to adjust analyses which include a considerable number of diabetics for antidiabetic drugs.