Abstract Body: In this study, we tested the hypothesis that α₁-antagonist use is associated with the onset of lower-extremity (LE) venous disease.

METHODS
We conducted a retrospective cohort study to examine the effect of α₁-blocker exposure on venous disease incidence. At the initial visit, all participants were verified to be free of venous disease by venous duplex ultrasonography. Participants were followed longitudinally, and a follow-up ultrasound was performed to assess for incident venous disease. Follow-up duration ranged from 9 to 13 years.

To further evaluate whether α₁-antagonist use was associated with symptomatic manifestations of venous disease, we conducted a cross-sectional study on a separate sample. All participants completed a survey assessing major symptoms of LE venous disease (heavy legs, aching legs, swelling, night cramps, restless legs, throbbing, itching, and/or tingling). Logistic regression was used to test for associations between α₁-antagonist use and venous disease symptoms, adjusting for age, sex, diabetes (DM) and smoking.

RESULTS
Our cohort study included 821 participants, of whom 14 were taking an α₁-blocker. The mean age at enrollment was 58 years; 65% of the cohort were female, 5% had DM, and 55% were never-smokers. A total of 330 subjects developed incident venous disease during follow-up. α₁-blocker use was associated with a 43% higher risk of venous disease (RR = 1.43, AR% = 30%, NNH = 5.8); however, this association was not statistically significant (Fisher’s test, p = 0.27; 95% CI 0.6–7.1).

To assess whether α₁-antagonist use was associated with self-reported venous symptoms, we performed a cross-sectional analysis of 1,056 individuals, of whom 25 were taking an α₁-blocker and 534 had venous disease. The mean age was 70 years; 67% were female, 10% had DM, and 67% were never-smokers. We did not find a significant association between α₁-blocker use and reports of any venous disease symptoms (p = 0.34), although the trend was positive (OR = 1.52). However, we found that α₁-antagonist use was associated with higher odds of restless legs (OR = 3.3; p = 0.073; 95% CI: 0.73–10.94). Suggestive but non-significant positive associations were also found for leg swelling (OR = 1.87; p = 0.29) and burning (OR = 2.67; p = 0.38).

CONCLUSION
Our findings suggest that α₁-antagonist use may be a risk factor for the development of symptomatic LE venous disease. Further analyses with greater statistical power are warranted to validate this association.