Association of Renin-Angiotensin-Aldosterone System Inhibitor Usage Patterns with Midterm Amputation-Free Survival after Lower Extremity Bypass for Peripheral Arterial Disease

Published:August 22, 2022DOI:


      Different renin-angiotensin-aldosterone system inhibitor (RAASI) usage patterns exist among patients undergoing lower extremity bypass (LEB) for peripheral arterial disease. We studied the association of RAASI usage patterns with LEB outcomes to determine which pattern is associated with improved survival after LEB.


      We evaluated peripheral arterial disease patients who underwent LEB between January 2014 and December 2018 in the Vascular Quality Initiative–Medicare matched database. Study cohorts included no RAASI use, preoperative RAASI use only, postoperative RAASI use only, and continuous RAASI use both preoperatively and postoperatively. Logistic and Cox regression was used to adjust for potential confounders. Primary outcome was 2-year amputation-free survival (AFS).


      Of 19,012 patients included, 1,574 (8.3%) were on RAASIs preoperatively only, 1,051 (5.5%) postoperatively only, and 8,484 (45.2%) continuously. Compared to no RAASI use, isolated preoperative RAASI use was associated with 2.8-fold increased odds of 30-day mortality (adjusted Odds Ratio, 2.75; 95% confidence interval [CI], 2.15–3.51; P < 0.001) whereas continuous RAASI use had 56% lower odds of 30-day mortality (adjusted Odds Ratio, 0.44; 95% CI, 0.34–0.58; P < 0.001). Two-year AFS was 63.2% for no RAASI use and 60.4%, 66.2%, and 73.4% for preoperative, postoperative, and continuous RAASI use, respectively (P < 0.001). While no RAASI use and postoperative RAASI use had comparable adjusted risks of 2-year major amputation or death (adjusted Hazard Ratio [aHR], 0.94; 95% CI, 0.83–1.06; P = 0.312), this risk was 14% higher for preoperative RAASI use only (aHR, 1.14; 95% CI, 1.04–1.26; P = 0.006) and 23% lower for continuous RAASI use (aHR, 0.77; 95% CI, 0.72–0.82; P < 0.001).


      Isolated preoperative RAASI use was associated with worse 30-day mortality and 2-year AFS, while continuous RAASI use was associated with improved 30-day mortality and 2-year AFS. Optimum survival benefit may be derived from continuous RAAS inhibition in the preoperative and postoperative periods.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Annals of Vascular Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Conte M.S.
        • Bradbury A.W.
        • Kolh P.
        • et al.
        Global vascular guidelines on the management of chronic limb-threatening ischemia.
        J Vasc Surg. 2019; 69: 3S-125S.e40
        • Fowkes F.G.R.
        • Rudan D.
        • Rudan I.
        • et al.
        Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.
        Lancet. 2013; 382: 1329-1340
        • Pande R.L.
        • Perlstein T.S.
        • Beckman J.A.
        • et al.
        Secondary prevention and mortality in peripheral artery disease: national health and nutrition examination study, 1999 to 2004.
        Circulation. 2011; 124: 17-23
        • Subherwal S.
        • Patel M.R.
        • Kober L.
        • et al.
        Missed opportunities: despite improvement in use of cardioprotective medications among patients with lower-extremity peripheral artery disease, underuse remains.
        Circulation. 2012; 126: 1345-1354
        • Armstrong E.J.
        • Chen D.C.
        • Westin G.G.
        • et al.
        Adherence to guideline-recommended therapy is associated with decreased major adverse cardiovascular events and major adverse limb events among patients with peripheral arterial disease.
        J Am Heart Assoc. 2014; 3: e000697
        • Chung J.
        • Timaran D.A.
        • Modrall J.G.
        • et al.
        Optimal medical therapy predicts amputation-free survival in chronic critical limb ischemia.
        J Vasc Surg. 2013; 58: 972-980
        • Coveney A.P.
        • O’Brien G.C.
        • Fulton G.J.
        ACE up the sleeve - are vascular patients medically optimized?.
        Vasc Health Risk Manag. 2011; 7: 15-21
        • Feringa H.H.H.
        • Van Waning V.H.
        • Bax J.J.
        • et al.
        Cardioprotective medication is associated with improved survival in patients with peripheral arterial disease.
        J Am Coll Cardiol. 2006; 47: 1182-1187
        • Kray J.E.
        • Dombrovskiy V.Y.
        • Vogel T.R.
        Use of angiotensin-converting enzyme inhibitors and freedom from amputation after lower extremity revascularization.
        Vasc Health Risk Manag. 2017; 13: 269-274
        • Beckwith C.
        • Munger M.A.
        Effect of angiotensin-converting enzyme inhibitors on ventricular remodeling and survival following myocardial infarction.
        Ann Pharmacother. 1993; 27: 755-766
        • Yusuf S.
        • Sleight P.
        • Pogue J.
        • et al.
        • Heart Outcomes Prevention Evaluation Study Investigators
        Effects of an angiotensin-converting–enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.
        N Engl J Med. 2000; 342: 145-153
        • Unkart J.T.
        • Allison M.A.
        • Abdelmalek J.A.
        • et al.
        Relation of plasma renin activity to subclinical peripheral and coronary artery disease (from the multiethnic study of atherosclerosis).
        Am J Cardiol. 2020; 125: 1794-1800
        • Cronenwett J.L.
        • Kraiss L.W.
        • Cambria R.P.
        The society for vascular surgery vascular quality initiative.
        J Vasc Surg. 2012; 55: 1529-1537
        • Mao J.
        • Etkin C.D.
        • Lewallen D.G.
        • et al.
        Creation and validation of linkage between orthopedic registry and administrative data using indirect identifiers.
        J Arthroplasty. 2019; 34: 1076-1081.e0
        • Halkin A.
        • Keren G.
        Potential indications for angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease.
        Am J Med. 2002; 112: 126-134
        • López-Sendón J.
        • Members T.F.
        • Swedberg K.
        • et al.
        Expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease: the Task Force on ACE-inhibitors of the European Society of Cardiology.
        Euro Heart J. 2004; 25: 1454-1470
        • Borer J.S.
        Angiotensin-converting enzyme inhibition: a landmark advance in treatment for cardiovascular diseases.
        Eur Heart J Suppl. 2007; 9E: E2-E9
        • Gerhard-Herman M.D.
        • Gornik H.L.
        • Barrett C.
        • et al.
        2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive Summary: a report of the American college of cardiology/American Heart Association task force on clinical practice guidelines.
        Circulation. 2017; 135: e686-e725
        • Furberg C.D.
        • Wright J.T.
        • Davis B.R.
        • et al.
        Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).
        J Am Med Assoc. 2002; 288: 2981-2997
        • Yusuf S.
        • Phil D.
        • Teo K.K.
        • et al.
        Telmisartan, ramipril, or both in patients at high risk for vascular events.
        N Engl J Med. 2008; 358: 1547-1559
        • Bodewes T.C.F.
        • Darling J.D.
        • O’Donnell T.F.X.
        • et al.
        Long-term mortality benefit of renin-angiotensin system inhibitors in patients with chronic limb-threatening ischemia undergoing vascular intervention.
        J Vasc Surg. 2018; 67: 800-808.e1
        • Roshanov P.S.
        • Rochwerg B.
        • Patel A.
        • et al.
        Withholding versus continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before noncardiac SurgeryAn analysis of the vascular events in noncardiac surgery patIents cOhort evaluatioN prospective cohort.
        Anesthesiology. 2017; 126: 16-27