RAS Inhibitors Show Promise for CLTI Patients After Interventions


Physicians should consider prescribing high-dose angiotensin inhibitors for patients with chronic limb-threatening ischemia (CLTI), a recent study from Harvard University suggests.

The report was published in the March edition of the Journal of Vascular Surgery by researchers from the Division of Vascular and Endovascular Surgery from the Beth Israel Deaconess Medical Center led by vascular surgeon Dr. Marc Schermerhorn.

The team 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.

In this population, RAS inhibition resulted in:
• Reduced mortality (67% versus 54% survival at three years)
• Lower 30-day myocardial infarction (1.6% versus 4.3%)
• No difference in major adverse limb events, amputation, or reinterventions

“These benefits were restricted to those prescribed high-dose RAS inhibition, and not realized in those on lower doses,” noted first author Dr. Thomas Bodewes. As such, the authors recommend that, “physicians should strive to maintain patients on high-dose RAS inhibition, provided that such doses are tolerated in terms of blood pressure.”
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 renin-angiotensin system (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
• Enhanced fibrinolysis

Despite this evidence, questions remain. The authors note 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.
There are relatively modest number of non-white 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.

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