Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use is associated with reduced major adverse cardiovascular events among patients with critical limb ischemia

Abstract

Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are recommended for secondary prevention in peripheral artery disease, but their effectiveness in patients with critical limb ischemia (CLI) is uncertain. We reviewed 464 patients with CLI who underwent diagnostic angiography or endovascular intervention from 2006-2013 at a multidisciplinary vascular center. ACEI or ARB use was assessed at the time of angiography. Major adverse cardiovascular events (MACE), mortality, and major adverse limb events (MALE) were assessed during three-year follow-up. Propensity weighting was used to adjust for baseline differences between patients taking and not taking ACEIs or ARBs. ACEIs or ARBs were prescribed to 269 (58%) patients. Patients prescribed ACEIs or ARBs had more baseline comorbidities including diabetes and hypertension (p<0.05). Patients prescribed ACEIs or ARBs had lower three-year unadjusted rates of MACE (40% versus 47%) and mortality (33% versus 43%). After propensity weighting, ACEI or ARB use was associated with significantly lower rates of MACE (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.58-0.99, p=0.04) and overall mortality (HR 0.71, 95% CI 0.53-0.95, p=0.02). There was no significant association between ACEI or ARB use and MALE (HR 0.97, 95% CI 0.69-1.35, p=0.2) or major amputation (HR 0.74, 95% CI 0.47-1.18, p=0.1). ACEI/ARB use is associated with lower MACE and mortality in patients with CLI, but there was no effect on limb-related outcomes.

Long-term outcomes in patients with critical limb ischemia and heart failure with preserved or reduced ejection fraction

“…Identifying high-risk patients and optimizing medical management of co-morbidities is critical to improving outcomes in this challenging patient population. [18][19][20][21]…”

Contemporary evaluation and management of lower extremity peripheral artery disease

“…In particular, ramipril has been shown to retard atherosclerotic progression in the carotid arteries and to reduce a composite endpoint of MI, stroke or cardiovascular death in patients with vascular disease 38. Further, the use of an ACE inhibitor or angiotensin receptor blocker in patients with CLI has been associated with significant reductions in MACE and mortality 39. Based on this, current consensus guidelines include a IIa recommendation supporting the use of ACE inhibitors in patients with symptomatic PAD regardless of blood pressure 11…”

Vascular specialist response to Medicare Evidence Development Coverage Advisory Committee (MEDCAC) panel on peripheral artery disease of the lower extremities

“…However, there are no randomized clinical trials in patients with CLI that have shown a decrease in revascularization rate, an increase in patency, a lower amputation rate, or faster wound healing with medical therapy alone. 21 A number of observational and single center studies have shown that patients with PAD and CLI are under-treated with guideline-recommended therapies (anti-platelet therapy, statins, and antihypertensive therapies). 22 Furthermore, under-treatment with guideline-recommended therapies was associated with increased repeat revascularization and amputation in patients undergoing revascularization.…”