ACE Inhibitors and Diabetic Foot Ulcers

NewsBot · Sep 16, 2010

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The differential effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers with respect to foot ulcer and limb amputation in those with diabetes.
Margolis DJ, Hoffstad O, Thom S, Bilker W, Maldonado AR, Cohen RM, Aronow BJ, Crombleholme T.
Wound Repair Regen. 2010 Sep;18(5)

Diabetic foot ulcers (DFU) or lower extremity amputation (LEA) are complications of diabetes. In those with diabetes, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are commonly used to prevent the progression of kidney disease. Recent studies have indicated that angiotensin may affect angiogenesis and wound repair. Our goal was to evaluate in those with diabetes the likelihood of developing a DFU or LEA among users of ACEi or ARB using a retrospective cohort design of general practices in the United Kingdom. We studied 40,342 individuals at least 35 years of age with diabetes who were first prescribed ACEi or ARB between 1995 and 2006. A total of 35,153 individuals were treated with ACEi, 12,437 individuals with ARB, and 7,310 both. The hazard ratio for DFU was 0.50 (95% confidence intervals: 0.43, 0.59), showing an increased risk of DFU for those using ACEi vs. ARB. The hazard ratio for LEA was 0.72 (0.48, 1.01). However, among those with lower extremity peripheral arterial disease the hazard ratio was 0.45 (0.22, 0.91) for the new onset of a LEA. In conclusion, among those with diabetes, exposure to ACEi as compared with ARB increases the risk of developing a DFU or LEA
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NewsBot · Mar 6, 2022

Healing of diabetic foot ulcers is independently associated with the use of angiotensin receptor blockers but not with those of diuretics and angiotensin conversion enzyme inhibitors
Marion Lapray et al
Diabetes Metab. 2022 Mar 1;101336

Aim: Dysregulation of the renin angiotensin system (RAS) has been proven in diabetic animal models, and studies in humans show that diuretic use is associated with lower limb amputation in diabetes. While patients with diabetes are often treated with diuretics and RAS blockers, the association between wound healing and these treatments is still unknown. We aimed to determine whether the use of diuretics and RAS blockers could influence healing of diabetic foot ulcers (DFU).

Methods: Two hundred seventy-six patients referred to a specialized diabetes foot care unit for a new foot ulcer were included in this retrospective observational study.

Results: Healing rate was significantly higher in patients not treated with diuretics than in those receiving diuretics (75.9 vs. 62.9%, P = 0.026) and in patients treated with angiotensin receptor blockers (ARB) than in those not treated with ARB (79.5 vs 64.4%, P = 0.012). The difference was not significant for angiotensin conversion enzyme inhibitor use. ARB use was independently and positively associated with wound healing in a multivariate adjusted model including several factors affecting wound healing (odds ratio (OR) 2.79 [1.13, 6.86] P = 0.025). Diuretic use was negatively associated with wound healing in univariate analysis (OR 0.54 [0.32, 0.91] P = 0.02) but not in multivariate adjusted analysis (OR 0.53 [0.26, 1.10] P = 0.088).

Conclusions: This novel study found that ARB use is independently and positively associated with wound healing in 276 patients with DFU. On the contrary, diuretics were associated with healing rate only at univariate analysis. Further prospective studies are needed to confirm our findings.
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NewsBot · May 22, 2022

Renin-Angiotensin-Aldosterone System Inhibitors, Statins, and Beta-Blockers in Diabetic Patients With Critical Limb Ischemia and Foot Lesions
Paolo Cimaglia et al
J Cardiovasc Pharmacol Ther. Jan-Dec 2022

Medical therapy for secondary prevention is known to be under-used in patients with peripheral artery disease (PAD). Few data are available on the subgroup with critical limb ischemia (CLI). Prescription of cardiovascular preventive therapies was recorded at discharge in a large, prospective cohort of patients admitted for treatment of CLI and foot lesions, stratified for coronary artery disease (CAD) diagnosis. All patients were followed up for at least 1 year. The primary endpoint was major adverse cardiovascular events (MACE). 618 patients were observed for a median follow-up of 981 days. Renin-angiotensin-aldosterone system (RAAS) inhibitors, statins, beta-blockers, and antithrombotic drugs were prescribed in 52%, 80%, 51%, and 99% of patients, respectively. However, only 43% of patients received optimal medical therapy (OMT), defined as the combination of RAAS inhibitor plus statin plus at least one antithrombotic drug. It was observed that the prescription of OMT was not affected by the presence of a CAD diagnosis. On the other hand, it was noticed that the renal function affected the prescription of OMT. OMT was independently associated with MACE (HR 0.688, 95%CI 0.475-0.995, P = .047) and, after propensity matching, also with all-cause mortality (HR 0.626, 95%CI 0.409-0.958, P = .031). Beta-blockers prescription was not associated with any outcome. In conclusion, patients with critical limb ischemia are under-treated with cardiovascular preventive therapies, irrespective of a CAD diagnosis. This has consequences on their prognosis.
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