Advertisement

Variability in Antithrombotic Therapy After Infrainguinal Lower Extremity Bypass

Published:September 19, 2022DOI:https://doi.org/10.1016/j.avsg.2022.08.016

      Abstract

      Objectives

      Antiplatelet monotherapy is recommended after infrainguinal lower extremity bypass (LEB). However, there is a paucity of high-quality data to guide therapy, and antiplatelet therapy is often prescribed in combination with anticoagulation. We therefore aimed to assess the variability in use of antithrombotic therapy after infrainguinal LEB.

      Methods

      The Vascular Quality Initiative dataset (2015-2021) was retrospectively reviewed to determine discharge patterns of antithrombotic therapy for all patients undergoing infrainguinal LEB. Monotherapy on discharge was defined as either single antiplatelet therapy (SAPT) or single anticoagulant (SAC). Combination therapy was dual antiplatelet therapy (DAPT), anticoagulant + antiplatelet (ACAP), or triple therapy. Hierarchical multivariable logistic regression with random effects for physician and center was used to identify predictors of combination therapy. Median odds ratios (MOR) were derived to quantify degree of variability in antithrombotic therapy.

      Results

      There were 29,507 patients undergoing infrainguinal LEB (monotherapy = 10,634 vs combination therapy = 18,873). SAPT (90.6%) was the most common form of monotherapy, while DAPT (57.7%) and ACAP (34.6%) were the most common combination therapies. Patients undergoing LEB to popliteal targets were more likely to be prescribed monotherapy (SAC or SAPT) than to infra-popliteal targets (60.6% vs 56.6%, P<.001). Combination therapy (DAPT, ACAP, or triple therapy) was more often used in patients with tibial or plantar arteries as the bypass target. Patients undergoing bypass using autogenous vein were more likely to receive monotherapy compared with those receiving other conduits (64.8% vs 52.9%, P<.001), while patients with prosthetic grafts were more likely to receive combination therapy (37.9% vs 28.2%, P<.001). There were no significant differences in post-operative bleeding (P=.491) or 30-day mortality (P=.302) between the two groups. Prior peripheral vascular interventions (OR 1.89, 95% CI 1.79 - 1.99), concomitant peripheral vascular intervention (OR 1.83, 95% CI 1.66 - 2.02), prosthetic graft use (OR 1.74, 95% CI 1.64 - 1.85), prior percutaneous coronary intervention (OR 1.53, 95% CI 1.43 - 1.65), plantar distal target (OR 1.46, 95% CI 1.29 - 1.65), alternative conduits (OR 1.39, 95% CI 1.25 - 1.53), and tibial distal targets (OR 1.36, 95% CI 1.28 - 1.44) were independent predictors of combination therapy in a multivariable regression model. Upon adjusting for patient-level factors, there was significant physician-level (MOR: 1.65, 95% CI 1.61-1.67) and center-level (MOR: 1.64, 95% CI 1.57-1.69) variability in the selection of antithrombotic therapy.

      Conclusions

      Significant physician- and center-level variability in the use of antithrombotic regimens after infrainguinal bypass reflects the paucity of available evidence to guide therapy. Pragmatic trials are needed to assess antithrombotic strategies and guide recommendations aimed at optimizing cardiovascular and graft-specific outcomes after lower extremity bypass.

      Keywords

      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:

      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

      9. References

        • Fowkes F.G.
        • 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
        • Nehler M.R.
        • Duval S.
        • Diao L.
        • et al.
        Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population.
        J Vasc Surg. 2014; 60: 686-695 e2
        • Rothwell P.M.
        • Coull A.J.
        • Silver L.E.
        • et al.
        Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study).
        Lancet. 2005; 366: 1773-1783
        • Albers M.
        • Battistella V.M.
        • Romiti M.
        • Rodrigues A.A.
        • Pereira C.A.
        Meta-analysis of polytetrafluoroethylene bypass grafts to infrapopliteal arteries.
        J Vasc Surg. 2003; 37: 1263-1269
        • Albers M.
        • Romiti M.
        • Braganca Pereira C.A.
        • Fonseca R.L.
        • da Silva Junior M.
        A meta-analysis of infrainguinal arterial reconstruction in patients with end-stage renal disease.
        Eur J Vasc Endovasc Surg. 2001; 22: 294-300
        • Albers M.
        • Romiti M.
        • Brochado-Neto F.C.
        • De Luccia N.
        • Pereira C.A.
        Meta-analysis of popliteal-to-distal vein bypass grafts for critical ischemia.
        J Vasc Surg. 2006; 43: 498-503
        • Albers M.
        • Romiti M.
        • Brochado-Neto F.C.
        • Pereira C.A.
        Meta-analysis of alternate autologous vein bypass grafts to infrapopliteal arteries.
        J Vasc Surg. 2005; 42: 449-455
        • Albers M.
        • Romiti M.
        • Pereira C.A.
        • Antonini M.
        • Wulkan M.
        Meta-analysis of allograft bypass grafting to infrapopliteal arteries.
        Eur J Vasc Endovasc Surg. 2004; 28: 462-472
        • Suckow B.D.
        • Kraiss L.W.
        • Stone D.H.
        • et al.
        Comparison of graft patency, limb salvage, and antithrombotic therapy between prosthetic and autogenous below-knee bypass for critical limb ischemia.
        Ann Vasc Surg. 2013; 27: 1134-1145
        • Sarac T.P.
        • Huber T.S.
        • Back M.R.
        • et al.
        Warfarin improves the outcome of infrainguinal vein bypass grafting at high risk for failure.
        J Vasc Surg. 1998; 28: 446-457
        • Dorffler-Melly J.
        • Buller H.R.
        • Koopman M.M.
        • Prins M.H.
        Antithrombotic agents for preventing thrombosis after infrainguinal arterial bypass surgery.
        Cochrane Database Syst Rev. 2003; : CD000536
        • Liang N.L.
        • Baril D.T.
        • Avgerinos E.D.
        • Leers S.A.
        • Makaroun M.S.
        • Chaer R.A.
        Comparative effectiveness of anticoagulation on midterm infrainguinal bypass graft patency.
        J Vasc Surg. 2017; 66: 499-505 e2
        • 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: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2017; 69: e71-e126
        • Alonso-Coello P.
        • Bellmunt S.
        • McGorrian C.
        • et al.
        Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
        Chest. 2012; 141 (e669S-e90S)
        • Society for Vascular Surgery Lower Extremity Guidelines Writing G.
        • Conte M.S.
        • Pomposelli F.B.
        • et al.
        Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: management of asymptomatic disease and claudication.
        J Vasc Surg. 2015; 61: 2S-41S
        • Aboyans V.
        • Ricco J.B.
        • Bartelink M.E.L.
        • et al.
        2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).
        Rev Esp Cardiol (Engl Ed). 2018; 71: 111
        • 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
        • Committee C.S.
        A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee.
        Lancet. 1996; 348: 1329-1339
        • Anand S.S.
        Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (the Dutch Bypass Oral anticoagulants or Aspirin study). Lancet 2000; 355: 346-351.
        Vasc Med. 2001; 6: 61
        • Monaco M.
        • Di Tommaso L.
        • Pinna G.B.
        • Lillo S.
        • Schiavone V.
        • Stassano P.
        Combination therapy with warfarin plus clopidogrel improves outcomes in femoropopliteal bypass surgery patients.
        J Vasc Surg. 2012; 56: 96-105
        • Johnson W.C.
        • Williford W.O.
        Department of Veterans Affairs Cooperative S. Benefits, morbidity, and mortality associated with long-term administration of oral anticoagulant therapy to patients with peripheral arterial bypass procedures: a prospective randomized study.
        J Vasc Surg. 2002; 35: 413-421
        • Bhatt D.L.
        • Flather M.D.
        • Hacke W.
        • et al.
        Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.
        J Am Coll Cardiol. 2007; 49: 1982-1988
        • Cacoub P.P.
        • Bhatt D.L.
        • Steg P.G.
        • Topol E.J.
        • Creager M.A.
        • Investigators C.
        Patients with peripheral arterial disease in the CHARISMA trial.
        Eur Heart J. 2009; 30: 192-201
        • Warfarin Antiplatelet Vascular Evaluation Trial I.
        • Anand S.
        • Yusuf S.
        • et al.
        Oral anticoagulant and antiplatelet therapy and peripheral arterial disease.
        N Engl J Med. 2007; 357: 217-227
        • Belch J.J.
        • Dormandy J.
        • Committee C.W.
        • et al.
        Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.
        J Vasc Surg. 2010; 52 (33 e1-2): 825-833
        • Eikelboom J.W.
        • Connolly S.J.
        • Bosch J.
        • et al.
        Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.
        N Engl J Med. 2017; 377: 1319-1330
        • Eikelboom J.W.
        • Bhatt D.L.
        • Fox K.A.A.
        • et al.
        Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease.
        J Am Coll Cardiol. 2021; 78: 14-23
        • Bonaca M.P.
        • Bauersachs R.M.
        • Anand S.S.
        • et al.
        Rivaroxaban in Peripheral Artery Disease after Revascularization.
        N Engl J Med. 2020; 382: 1994-2004
        • Normand S.T.
        • Landrum M.B.
        • Guadagnoli E.
        • et al.
        Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: a matched analysis using propensity scores.
        J Clin Epidemiol. 2001; 54: 387-398
        • Larsen K.
        • Merlo J.
        Appropriate assessment of neighborhood effects on individual health: integrating random and fixed effects in multilevel logistic regression.
        Am J Epidemiol. 2005; 161: 81-88
        • Merlo J.
        • Chaix B.
        • Ohlsson H.
        • et al.
        A brief conceptual tutorial of multilevel analysis in social epidemiology: using measures of clustering in multilevel logistic regression to investigate contextual phenomena.
        J Epidemiol Community Health. 2006; 60: 290-297
        • Lee M.
        • Ahmed Z.V.
        • Huang J.
        • et al.
        Real-world antithrombotic treatment variability in patients undergoing peripheral vascular intervention: Insights from the VQI registry.
        Am Heart J. 2021; 244: 31-35
        • Brumberg R.S.
        • Back M.R.
        • Armstrong P.A.
        • et al.
        The relative importance of graft surveillance and warfarin therapy in infrainguinal prosthetic bypass failure.
        J Vasc Surg. 2007; 46: 1160-1166
        • Belkin N.
        • Stoecker J.B.
        • Jackson B.M.
        • et al.
        Effects of dual antiplatelet therapy on graft patency after lower extremity bypass.
        J Vasc Surg. 2021; 73: 930-939
        • Jackson M.R.
        • Johnson W.C.
        • Williford W.O.
        • Valentine R.J.
        • Clagett G.P.
        The effect of anticoagulation therapy and graft selection on the ischemic consequences of femoropopliteal bypass graft occlusion: results from a multicenter randomized clinical trial.
        J Vasc Surg. 2002; 35: 292-298
        • Bedenis R.
        • Lethaby A.
        • Maxwell H.
        • Acosta S.
        • Prins M.H.
        Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery.
        Cochrane Database Syst Rev. 2015; : CD000535
        • Debus E.S.
        • Nehler M.R.
        • Govsyeyev N.
        • et al.
        Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.
        Circulation. 2021; 144: 1104-1116