Background: This post-hoc subanalysis of the VEIN STEP study assessed the effectiveness of conservative treatment, particularly venoactive drugs (VAD), in reducing chronic venous disease (CVD) signs and symptoms and improving quality of life (QoL) for patients with type 2 diabetes (T2D) in a real-life setting. Methods: VEIN STEP was an observational, prospective study conducted in adult outpatients who consulted for symptomatic CVD (NCT04574375). CVD symptoms (10-cm Visual Analog Scale and Patient Global Impression of Change), disease severity (Venous Clinical Severity Score), and QoL (Chronic Venous Insufficiency Questionnaire CIVIQ-14) were assessed. Results: Overall, 6084 patients were analyzed, of whom 702 (11.5%) had T2D. These patients were more likely to be older, present with a more advanced CEAP class, have a higher body mass index, greater symptom severity and reduced QoL scores than those without T2D (p< 0.001 for all). Almost all patients with T2D (97.3%) received VAD-based treatment, mainly micronized purified flavonoid fraction (MPFF, 72.2%) or diosmin (24.6%). After 4 weeks, conservative therapy was associated with significant improvements in CVD symptoms and QoL (p< 0.001). Physicians also noted a significant improvement in disease severity (p< 0.001). The decrease in global symptom intensity was significantly greater among patients treated with MPFF than in those treated with diosmin (mean − 2.7± 1.8 vs − 2.0± 1.8, p=0.004). Greater reductions in symptom intensity were also observed in patients treated with MPFF for pain (p=0.011), leg heaviness (p=0.006), and swelling (p=0.014), with a tendency for greater improvement of cramps. QoL improved for patients receiving MPFF and those receiving diosmin, with changes in CIVIQ-14 global index score of − 21.3± 15.8 and − 15.5± 14.6, respectively. Conclusion: These findings indicate that patients with concomitant CVD and T2D are more likely to have greater symptom severity and disease burden. In such patients, VAD-based conservative therapy, particularly MPFF, was associated with significant improvements in CVD-related symptoms and QoL. Plain Language Summary: Chronic venous disease (CVD) is a common condition that often coexists with type 2 diabetes (T2D), with which it shares many risk factors such as aging, obesity, and inactive lifestyles. The VEIN STEP observational study included over 6,000 patients with CVD, 11.5% of whom also had T2D. Subjects with both conditions had worse symptoms, more severe disease, and lower quality of life than those with CVD alone. For the majority, interventions consisted of non-surgical treatments such as compression therapy and venoactive drugs, especially micronized purified flavonoid fraction (MPFF) and diosmin. There is a strong connection between CVD and T2D and the presence of one condition should prompt physicians to examine the patient for the other. This study shows that early diagnosis and treatment can significantly reduce CVD symptoms and improve quality of life. It also calls for more attention to managing CVD in people with T2D to reduce complications and improve outcomes. Keywords: chronic venous disease, conservative therapy, micronized purified flavonoid fraction, observational study, type 2 diabetes, venoactive drug
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