A prospective observational study to evaluate a possible relationship between vitamin K antagonist therapy and risk of peripheral arterial disease in patients with type 2 diabetes

Diabetes Obes Metab. 2024 Aug;26(8):3290-3298. doi: 10.1111/dom.15656. Epub 2024 May 15.

Abstract

Aim: The use of vitamin K antagonists (VKAs) may increase the risk of peripheral arterial disease (PAD) because vitamin K is a strong inhibitor of medial arterial calcification. Type 2 diabetes (T2D) exposes patients to an increased risk of PAD. We examined how the use of VKAs modulates the risk of incident PAD in people with T2D.

Materials and methods: SURDIAGENE is a French cohort including 1468 patients with T2D with a prospective follow-up from 2002 to 2015. The primary outcome of the current analysis was the first occurrence of PAD, a composite of lower-limb amputation (LLA) or lower-limb revascularization. LLA and lower-limb revascularization were considered individually as secondary outcomes.

Results: During a 7-year median follow-up, PAD occurred in 147 (10%) of the 1468 participants. The use of VKAs was not significantly associated with the risk of PAD [multivariable adjusted hazard ratio (HR) 1.42, 95% confidence interval (CI), 0.88-2.31]. During the study period, LLA and lower-limb revascularization occurred in 82 (6%) and 105 (7%) participants, respectively. The use of VKAs was significantly associated with increased risk of LLA [multivariable adjusted HR 1.90 (95% CI, 1.04-3.47)], but not lower-limb revascularization [multivariable adjusted HR 1.08 (95% CI, 0.59-1.97)].

Conclusions: In this prospective study, we did not observe any excess risk of PAD requiring lower-limb revascularization in people with type 2 diabetes using VKAs. However, our data suggest a high risk of LLA in VKA users. Further studies are required to confirm this observation.

Keywords: cardiovascular disease; cohort study; diabetes complications; macrovascular disease; observational study; type 2 diabetes.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Amputation, Surgical* / statistics & numerical data
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Angiopathies* / epidemiology
  • Diabetic Angiopathies* / prevention & control
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Humans
  • Incidence
  • Lower Extremity / blood supply
  • Lower Extremity / surgery
  • Male
  • Middle Aged
  • Peripheral Arterial Disease* / epidemiology
  • Prospective Studies
  • Risk Factors
  • Vitamin K* / antagonists & inhibitors

Substances

  • Vitamin K
  • Anticoagulants