The incidence of cardiovascular and limb-specific adverse outcomes is higher in
peripheral arterial disease (PAD) patients with diabetes.
Metformin is associated with improved cardiovascular morbidity and mortality. 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 after intervention for PAD.
METHODS: Patients who underwent revascularization for chronic limb
ischemia (Rutherford 3-6) between June 2001 and December 2014 were retrospectively identified. Primary patency (PP), secondary patency (SP),
limb salvage (LS), major adverse limb events (MALE),
major adverse cardiac events (
MACE), and survival rates were compared using Kaplan-Meier and Cox regression.
RESULTS: One thousand sixty-four limbs in 1204 patients were identified (147
metformin, 196 other
hypoglycemics [
OH], 216
insulin, and 645 nondiabetics (nondiabetes mellitus [DM]). Non-DM had significantly lower incidence of CAD (46%) than
insulin (65%),
metformin (56%), and
OH groups (63%) (P < 0.001).
Insulin patients (17%) had significantly higher incidence of
end-stage renal disease (
ESRD) than non-DM (3%),
metformin (1.4%), and
OH groups (8%) (P < 0.001). Ninety four percent of patients in the
metformin group were on
aspirin, which was significantly higher than non-DM (86%),
OH (83%), and
insulin groups (86%) (P = 0.02). Similarly,
statin use was significantly higher in the
metformin group (71%) than in
OH (64%),
insulin (61%), and non-DM groups (55%) (P = 0.002). Majority of patients in the
insulin group presented with
critical limb ischemia (CLI) (93%), which was significantly greater than the
metformin (59%),
OH (72%), and non-DM groups (50%) (P < 0.001). Sixty-month PP was significantly greater in non-DM group (62%) (P = 0.005) in overall comparison with no significant difference between
metformin (56%),
OH (60%), and
insulin (51%) groups (P = 0.06). Sixty-month SP was similar in
metformin (76%),
OH (85%),
insulin (76%), and non-DM (80%) groups (P = 0.27). LS was significantly worse in
insulin group (62%) (P < 0.001) with no significant difference between
metformin (84%),
OH (83%), and non-DM (87%) groups (P = 0.45). Freedom from MALE at 60 months was 53% in the
insulin group, which was significantly worse as compared with
metformin (71%),
OH (70%), and non-DM (67%) groups (P = 0.001). Sixty-month survival was significantly improved in
metformin (60%) and non-DM (60%) groups as compared with that in
OH (41%) and
insulin groups (30%) (P < 0.001). Freedom from
MACE was significantly greater in
metformin (44%) and non-DM (52%) groups than that in
OH (37%) and
insulin groups (25%) (P < 0.001).
Metformin use (HR, 0.7 [0.5-0.9]; P = 0.008) was an independent factor associated with freedom from mortality.
CONCLUSIONS: