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Metformin Is Associated with Improved Survival and Decreased Cardiac Events With No Impact on Patency and Limb Salvage After Revascularization for Chronic Limb Ischemia
Sikandar Z. Khan, MBBS1, Mariel Rivero, MD2, Linda Harris, MD1, Maciej Dryjski, MD1, Gregory Cherr, MD1, Nader D. Nader, MD2, Hasan H. Dosluoglu, MD2.
1SUNY Buffalo, Buffalo, NY, USA, 2VA Western NY Healthcare System, Buffalo, NY, USA.

Objective(s): The incidence of cardiovascular and limb-specific adverse outcomes is higher in PAD patients with diabetes. Metformin is the first-line drug therapy for Type 2 diabetes and is associated with fewer adverse cardiovascular events. However, the effect of Metformin on limb-specific outcomes is unclear. The objective of this study was to assess the effect of Metformin on outcomes following intervention for PAD.
Methods: Patients who underwent revascularization for chronic limb ischemia (Rutherford 3-6) between 06/2001-12/2014 were retrospectively identified. Primary Patency (PP), Secondary Patency (SP), Limb Salvage (LS), Major Adverse Cardiac Events (MACE) and survival rates of patients on Metformin were compared to those not on Metformin using Kaplan-Meier and Cox regression.
Results: 1564 limbs in 1204 patients were identified (147 Metformin, 196 Other oral Hypoglycemics (OH), 216 Insulin only, 645 Non-diabetics). Non-diabetics had significantly lower incidence of coronary artery disease and hypertension as compared to other subgroups (P <.05). Statin and aspirin use was significantly higher in the Metformin group (P<.05). Insulin group had significantly greater number of patients with end-stage renal disease and CLI (P<.05). 60-month PP was significantly greater in non-diabetics 62% (P=.005) with no significant difference between Metformin 56%, OH 60% and Insulin 51% groups (P= .06). 60-month SP was similar in Metformin 76%, OH 85%, Insulin 76% and Non-Diabetics 80% (P= .272). LS was significantly worse in Insulin group 62% (P<.001) with no significant difference between Metformin 84%, OH 83% and Non-diabetic 87% (P= .451). 60-month survival was significantly improved in Metformin 60% and Non-diabetic 60% as compared to OH 41% and Insulin group 30% (P<.001).Freedom from MACE was significantly greater in Metformin 44% and Non-diabetic 52% as compared to OH 37% and Insulin group 25% (P<.001). Metformin use (HR 0.7 (0.5-0.9), P =0.008) was an independent factor associated with survival. (Figure)
Conclusions:
Metformin is not associated with improved patency or limb salvage rates but is independently associated with improved survival and decreased MACE in patients with PAD. Limb salvage was similar in non-diabetics and patients on Metformin and other oral hypoglycemics. Insulin use was associated with increase limb loss.


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