Renin-Angiotensin System Inhibitors Studied for Patients With Chronic Limb-Threatening Ischemia

February 28, 2018—The Society for Vascular Surgery (SVS) announced the publication of findings from a study demonstrating that physicians should consider prescribing high-dose angiotensin inhibitors for patients with chronic limb-threatening ischemia (CLTI). The study was published by researchers from the Division of Vascular and Endovascular Surgery from the Beth Israel Deaconess Medical Center led by Marc Schermerhorn, MD, in Journal of Vascular Surgery (2018;667:800–808).

According to the SVS, the investigators conducted a retrospective review of 1,161 patients between 2005 and 2014 and evaluated the effect of renin-angiotensin system (RAS) inhibition on mortality in patients undergoing revascularization (both endovascular and surgical bypass) for CLTI.

The investigators reported that in this population, RAS inhibition resulted in reduced mortality (67% vs 54% survival at 3 years), lower 30-day myocardial infarction rate (1.6% vs 4.3%), and no difference in major adverse limb events, amputation, or reinterventions.

In the SVS announcement, study investigator Thomas Bodewes, MD, noted, "These benefits were restricted to those prescribed high-dose RAS inhibition and not realized in those on lower doses." Because of this, the investigators recommended that, "physicians should strive to maintain patients on high-dose RAS inhibition, provided that such doses are tolerated in terms of blood pressure."

As explained in the SVS announcement, patients with CLTI are heavily burdened with atherosclerosis, which affects nearly all important vascular beds, including the cerebral, coronary, peripheral, renal, and mesenteric circulatory systems. A growing body of evidence suggests that RAS inhibition has multiple cardiovascular benefits including blood pressure control, decrease in preload and afterload, stabilization of plaque, inhibition of smooth muscle proliferation, improved vascular endothelial function, reduced ventricular hypertrophy, and enhanced fibrinolysis.

The SVS noted that despite this evidence, questions remain.

The study investigators cautioned that this was a retrospective single-institution review, and despite adjustment for multiple variables, the association between RAS inhibitor use and long-term outcomes may be confounded by other factors including some that were unmeasured. These factors include that there are relatively modest number of nonwhite patients, and actual use of the medications beyond hospital discharge among the study patients is unknown. There are potential side effects to the use of RAS inhibitors that providers must consider in the dosing of these medications. Larger confirmatory studies are needed to confirm these findings and strengthen the evidence, reported the SVS.