Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Systematic Review Article

Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis

Author(s): Marco De Carlo*, Giovanni Di Minno, Tobias Sayre, Mir Sohail Fazeli, Gaye Siliman and Claudio Cimminiello

Volume 19, Issue 5, 2021

Published on: 20 August, 2020

Page: [542 - 555] Pages: 14

DOI: 10.2174/1570161118666200820141131

open access plus

Abstract

Background: Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD.

Methods: We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses.

Results: We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65-0.93) and ticagrelor (HR 0.80; 95% CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95% CrI 0.43-1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed a significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk.

Conclusion: This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.

Keywords: Antiplatelet therapies, lower extremity artery disease, network meta-analysis, peripheral artery disease, systematic literature review, clopidogrel monotherapy.

Graphical Abstract
[1]
Fowkes FG, 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(9901): 1329-40.
[http://dx.doi.org/10.1016/S0140-6736(13)61249-0] [PMID: 23915883]
[2]
Aboyans V, Ricco JB, Bartelink MEL, et al. ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J 2018; 39(9): 763-816.
[http://dx.doi.org/10.1093/eurheartj/ehx095] [PMID: 28886620]
[3]
Gerhard-Herman MD, Gornik HL, 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(12): e686-725.
[http://dx.doi.org/10.1161/CIR.0000000000000470] [PMID: 27840332]
[4]
CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348(9038): 1329-39.
[http://dx.doi.org/10.1016/S0140-6736(96)09457-3] [PMID: 8918275]
[5]
Hiatt WR, Fowkes FG, Heizer G, et al. EUCLID Trial Steering Committee and Investigators. Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease. N Engl J Med 2017; 376(1): 32-40.
[http://dx.doi.org/10.1056/NEJMoa1611688] [PMID: 27959717]
[6]
Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions version 60 2019.www.training.cochrane.org/handbook
[7]
Higgins JP, Altman DG, Gøtzsche PC, et al. Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
[http://dx.doi.org/10.1136/bmj.d5928] [PMID: 22008217]
[8]
Dias S, Welton NJ, Sutton AJ, Ades AE. NICE Decision Support Unit Technical Support Documents NICE DSU Technical Support Document 2: A Generalised Linear Modelling Framework for Pairwise and Network Meta-Analysis of Randomised Controlled Trials National Institute for Health and Care Excellence. London: NICE 2014.
[9]
Anand SS, Bosch J, Eikelboom JW, et al. COMPASS Investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2018; 391(10117): 219-29.
[http://dx.doi.org/10.1016/S0140-6736(17)32409-1] [PMID: 29132880]
[10]
Anand SS, Caron F, Eikelboom JW, et al. Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease: The COMPASS Trial. J Am Coll Cardiol 2018; 71(20): 2306-15.
[http://dx.doi.org/10.1016/j.jacc.2018.03.008] [PMID: 29540326]
[11]
Jackson MR, Johnson WC, Williford WO, Valentine RJ, Clagett GP. 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(2): 292-8.
[http://dx.doi.org/10.1067/mva.2002.120383] [PMID: 11854727]
[12]
Johnson WC, Williford WO, Corson JD, Padberg FT Jr. Hemorrhagic complications during long-term postoperative warfarin administration in patients undergoing lower extremity arterial bypass surgery. Vascular 2004; 12(6): 362-8.
[http://dx.doi.org/10.2310/6670.2004.00043] [PMID: 15895759]
[13]
Johnson WC, Williford WO. Department of Veterans Affairs Cooperative Study #362. 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(3): 413-21.
[http://dx.doi.org/10.1067/mva.2002.121847] [PMID: 11877686]
[14]
Koppensteiner R, Spring S, Amann-Vesti BR, et al. Low-molecular-weight heparin for prevention of restenosis after femoropopliteal percutaneous transluminal angioplasty: a randomized controlled trial. J Vasc Surg 2006; 44(6): 1247-53.
[http://dx.doi.org/10.1016/j.jvs.2006.07.044] [PMID: 17145426]
[15]
Li H, Zhang F, Liang G, et al. A prospective randomized controlled clinical trial on clopidogrel combined with warfarin versus clopidogrel alone in the prevention of restenosis after endovascular treatment of the femoropopliteal artery. Ann Vasc Surg 2013; 27(5): 627-33.
[http://dx.doi.org/10.1016/j.avsg.2012.07.011] [PMID: 23540665]
[16]
Moll F, Baumgartner I, Jaff M, et al. ePAD Investigators. Edoxaban Plus Aspirin vs Dual Antiplatelet Therapy in Endovascular Treatment of Patients With Peripheral Artery Disease: Results of the ePAD Trial. J Endovasc Ther 2018; 25(2): 158-68.
[http://dx.doi.org/10.1177/1526602818760488] [PMID: 29552984]
[17]
Monaco M, Di Tommaso L, Pinna GB, Lillo S, Schiavone V, Stassano P. Combination therapy with warfarin plus clopidogrel improves outcomes in femoropopliteal bypass surgery patients. J Vasc Surg 2012; 56(1): 96-105.
[http://dx.doi.org/10.1016/j.jvs.2012.01.004] [PMID: 22551909]
[18]
Patel MR, Becker RC, Wojdyla DM, et al. Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared with clopidogrel: Data from the PLATO Trial. Eur J Prev Cardiol 2015; 22(6): 734-42.
[http://dx.doi.org/10.1177/2047487314533215] [PMID: 24830710]
[19]
Jones WS, Tricoci P, Huang Z, et al. Vorapaxar in patients with peripheral artery disease and acute coronary syndrome: insights from Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER). Am Heart J 2014; 168(4): 588-96.
[http://dx.doi.org/10.1016/j.ahj.2014.06.017] [PMID: 25262270]
[20]
Bonaca MP, Bhatt DL, Storey RF, et al. Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. J Am Coll Cardiol 2016; 67(23): 2719-28.
[http://dx.doi.org/10.1016/j.jacc.2016.03.524] [PMID: 27046162]
[21]
Soga Y, Iida O, Hirano K, Suzuki K, Yokoi H, Nobuyoshi M. Restenosis after stent implantation for superficial femoral artery disease in patients treated with cilostazol. Catheter Cardiovasc Interv 2012; 79(4): 541-8.
[http://dx.doi.org/10.1002/ccd.23304] [PMID: 21805619]
[22]
Fiotti N, Altamura N, Cappelli C, Schillan M, Guarnieri G, Giansante C. Long term prognosis in patients with peripheral arterial disease treated with antiplatelet agents. Eur J Vasc Endovasc Surg 2003; 26(4): 374-80.
[http://dx.doi.org/10.1016/S1078-5884(03)00318-6] [PMID: 14511998]
[23]
Armstrong EJ, Anderson DR, Yeo KK, et al. Association of dual-antiplatelet therapy with reduced major adverse cardiovascular events in patients with symptomatic peripheral arterial disease J Vasc Surg 2015; 62: 157-65.
[http://dx.doi.org/10.1016/j.jvs.2015.01.051]
[24]
Arcan JC, Blanchard J, Boissel JP, Destors JM, Panak E. Multicenter double-blind study of ticlopidine in the treatment of intermittent claudication and the prevention of its complications. Angiology 1988; 39(9): 802-11.
[http://dx.doi.org/10.1177/000331978803900904] [PMID: 3048155]
[25]
Balsano F, Coccheri S, Libretti A, et al. Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial. J Lab Clin Med 1989; 114(1): 84-91.
[PMID: 2661700]
[26]
Balsano F, Violi F. The ADEP Group. Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. Circulation 1993; 87(5): 1563-9.
[http://dx.doi.org/10.1161/01.CIR.87.5.1563] [PMID: 8491012]
[27]
Becquemin JP. Effect of ticlopidine on the long-term patency of saphenous-vein bypass grafts in the legs. N Engl J Med 1997; 337(24): 1726-31.
[http://dx.doi.org/10.1056/NEJM199712113372404] [PMID: 9392698]
[28]
Beebe HG, Dawson DL, Cutler BS, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med 1999; 159(17): 2041-50.
[http://dx.doi.org/10.1001/archinte.159.17.2041] [PMID: 10510990]
[29]
Belch JJ, Dormandy J, 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: 825-33.
[http://dx.doi.org/10.1016/j.jvs.2010.04.027]
[30]
Berger J, Heizer G, Baumgartner I, et al. Ticagrelor in patients wtih symptomatic peripheral artery disease and prior coronary artery disease. Eur Heart J 2017; 23(6): 523-30.
[http://dx.doi.org/10.1177/1358863X18775594]
[31]
Berger JS, Abramson BL, Lopes RD, et al. Ticagrelor versus clopidogrel in patients with symptomatic peripheral artery disease and prior coronary artery disease: Insights from the EUCLID trial. Vasc Med 2018; 23(6): 523-30.
[http://dx.doi.org/10.1177/1358863X18775594] [PMID: 29992857]
[32]
Bergqvis D. Study group on pharmacological treatment after PTA. Platelet inhibition with ASA/dipyridamole after percutaneous balloon angioplasty in patients with symptomatic lower limb arterial disease. A prospective double-blind trial. Eur J Vasc Surg 1994; 8: 83-8.
[http://dx.doi.org/10.1016/S0950-821X(05)80126-4] [PMID: 8307222]
[33]
Bhatt DL, Flather MD, Hacke W, et al. CHARISMA Investigators. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 2007; 49(19): 1982-8.
[http://dx.doi.org/10.1016/j.jacc.2007.03.025] [PMID: 17498584]
[34]
Blanchard J, Carreras LO, Kindermans M. Results of EMATAP: a double-blind placebo-controlled multicentre trial of ticlopidine in patients with peripheral arterial disease. Nouv Rev Fr Hematol 1994; 35(6): 523-8.
[PMID: 8152898]
[35]
Bonaca MP, Creager MA, Olin J, et al. Peripheral Revascularization in Patients With Peripheral Artery Disease With Vorapaxar: Insights From the TRA 2°P-TIMI 50 Trial. JACC Cardiovasc Interv 2016; 9(20): 2157-64.
[http://dx.doi.org/10.1016/j.jcin.2016.07.034] [PMID: 27765312]
[36]
Bonaca MP, Gutierrez JA, Creager MA, et al. Acute Limb Ischemia and Outcomes With Vorapaxar in Patients With Peripheral Artery Disease: Results From the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis in Myocardial Infarction 50 (TRA2°P-TIMI 50). Circulation 2016; 133(10): 997-1005.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019355] [PMID: 26826179]
[37]
Bonaca MP, Scirica BM, Creager MA, et al. Vorapaxar in patients with peripheral artery disease: results from TRA2°P-TIMI 50. Circulation 2013; 127: 1522-9.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000679]
[38]
Brass EP, Cooper LT, Morgan RE, Hiatt WR. A phase II dose-ranging study of the phosphodiesterase inhibitor K-134 in patients with peripheral artery disease and claudication. J Vasc Surg 2012; 55: 381-9.
[http://dx.doi.org/10.1016/j.jvs.2011.09.004] [PMID: 22119244]
[39]
Castelli P, Basellini A, Agus GB, et al. Thrombosis prevention with ticlopidine after femoropopliteal thromboendarterectomy. Int Surg 1986; 71(4): 252-5.
[PMID: 3549601]
[40]
Dawson DL, Cutler BS, Hiatt WR, et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 2000; 109(7): 523-30.
[http://dx.doi.org/10.1016/S0002-9343(00)00569-6] [PMID: 11063952]
[41]
Fagher B. Long-term effects of ticlopidine on lower limb blood flow, ankle/brachial index and symptoms in peripheral arteriosclerosis. A double-blind study. The STIMS Group in Lund. Swedish Ticlopidine Multicenter Study. Angiology 1994; 45(9): 777-88.
[http://dx.doi.org/10.1177/000331979404500905] [PMID: 8092543]
[42]
Hiatt W. A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID) 2017. Available at: https://clinicaltrials.gov/ct2/show/results/NCT01732822
[43]
Hiatt WR, Money SR, Brass EP. Long-term safety of cilostazol in patients with peripheral artery disease: the CASTLE study (Cilostazol: A Study in Long-term Effects). J Vasc Surg 2008; 47(2): 330-6.
[http://dx.doi.org/10.1016/j.jvs.2007.10.009] [PMID: 18155871]
[44]
Iida O, Yokoi H, Soga Y, et al. STOP-IC investigators. Cilostazol reduces angiographic restenosis after endovascular therapy for femoropopliteal lesions in the Sufficient Treatment of Peripheral Intervention by Cilostazol study. Circulation 2013; 127(23): 2307-15.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000711] [PMID: 23652861]
[45]
Janzon L, Bergqvist D, Boberg J, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. J Intern Med 1990; 227(5): 301-8.
[http://dx.doi.org/10.1111/j.1365-2796.1990.tb00164.x] [PMID: 2187948]
[46]
Jones WS, Baumgartner I, Hiatt WR, et al. International Steering Committee and Investigators of the EUCLID Trial. Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease. Circulation 2017; 135(3): 241-50.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.025880] [PMID: 27840336]
[47]
McCollum C, Alexander C, Kenchington G, Franks PJ, Greenhalgh R. Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial. J Vasc Surg 1991; 13(1): 150-61.
[http://dx.doi.org/10.1016/0741-5214(91)90022-M] [PMID: 1987387]
[48]
Milani M, Longoni A, Maderna M. Effects of picotamide, an antiplatelet agent, on cardiovascular, events in 438 claudicant patients with diabetes: a retrospective analysis of the ADEP study. Br J Clin Pharmacol 1996; 42(6): 782-5.
[http://dx.doi.org/10.1046/j.1365-2125.1996.00503.x] [PMID: 8971437]
[49]
Money SR, Herd JA, Isaacsohn JL, et al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg 1998; 27(2): 267-74.
[http://dx.doi.org/10.1016/S0741-5214(98)70357-X] [PMID: 9510281]
[50]
Neri Serneri GG, Coccheri S, Marubini E, Violi F. Drug Evaluation in Atherosclerotic Vascular Disease in Diabetics (DAVID) Study Group. Picotamide, a combined inhibitor of thromboxane A2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: the DAVID study. Eur Heart J 2004; 25(20): 1845-52.
[http://dx.doi.org/10.1016/j.ehj.2004.07.013] [PMID: 15474700]
[51]
Qamar A, Morrow DA, Bonaca MP, Eds. Efficacy and safety of vorapaxar on cardiovascular and limb outcomes in a broad population of patients with peripheral artery disease: analysis from TRA2P-TIMI 50.Vascular Medicine. London: SAGE Publications 2018.
[52]
Shigematsu H, Komori K, Tanemoto K, Harada Y, Nakamura M. Clopidogrel for Atherothrombotic Event Management in Patients with Peripheral Arterial Disease (COOPER) Study: Safety and Efficacy of Clopidogrel versus Ticlopidine in Japanese Patients. Ann Vasc Dis 2012; 5(3): 364-75.
[http://dx.doi.org/10.3400/avd.oa.12.00039] [PMID: 23555538]
[53]
Soga Y, Hamasaki T, Edahiro R, et al. STOP-IC investigators. Sustained effectiveness of cilostazol after endovascular treatment of femoropopliteal lesions: midterm follow-up from the sufficient treatment of peripheral intervention by cilostazol (STOP-IC) Study. J Endovasc Ther 2018; 25(3): 306-12.
[http://dx.doi.org/10.1177/1526602818771358] [PMID: 29706129]
[54]
Soga Y, Takahara M, Iida O, et al. Efficacy of CilostAzol for Below-the-Knee Artery Disease after Balloon AnGioplasty in PatiEnts with Severe Limb Ischemia (CABBAGE Trial). Ann Vasc Surg 2017; 45: 22-8.
[http://dx.doi.org/10.1016/j.avsg.2017.05.029] [PMID: 28600024]
[55]
Soga Y, Yokoi H, Kawasaki T, et al. Efficacy of cilostazol after endovascular therapy for femoropopliteal artery disease in patients with intermittent claudication. J Am Coll Cardiol 2009; 53(1): 48-53.
[http://dx.doi.org/10.1016/j.jacc.2008.09.020] [PMID: 19118724]
[56]
Strandness DE Jr, Dalman RL, Panian S, et al. Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study. Vasc Endovascular Surg 2002; 36(2): 83-91.
[http://dx.doi.org/10.1177/153857440203600202] [PMID: 11951094]
[57]
Strobl FF, Brechtel K, Schmehl J, et al. Twelve-month results of a randomized trial comparing mono with dual antiplatelet therapy in endovascularly treated patients with peripheral artery disease. J Endovasc Ther 2013; 20(5): 699-706.
[http://dx.doi.org/10.1583/13-4275MR.1] [PMID: 24093324]
[58]
Tepe G, Bantleon R, Brechtel K, et al. Management of peripheral arterial interventions with mono or dual antiplatelet therapy--the MIRROR study: a randomised and double-blinded clinical trial. Eur Radiol 2012; 22(9): 1998-2006.
[http://dx.doi.org/10.1007/s00330-012-2441-2] [PMID: 22569995]
[59]
Habib A, Petrucci G, Rocca B. Pathophysiology of Thrombosis in Peripheral Artery Disease. Curr Vasc Pharmacol 2020; 18(3): 204-14.
[http://dx.doi.org/10.2174/1570161117666190206234046] [PMID: 30727897]
[60]
Vrsalovic M, Aboyans V. Antithrombotic Therapy in Lower Extremity Artery Disease. Curr Vasc Pharmacol 2020; 18(3): 215-22.
[http://dx.doi.org/10.2174/1570161117666190206230516] [PMID: 30727898]
[61]
De Carlo M, Angelillis M, Liga R. Antithrombotic Therapy for Peripheral Revascularisation. Curr Vasc Pharmacol 2020; 18(3): 223-36.
[http://dx.doi.org/10.2174/1570161117666190206234606] [PMID: 30727899]
[62]
Navarese EP, Wernly B, Lichtenauer M, et al. Dual vs single antiplatelet therapy in patients with lower extremity peripheral artery disease - A meta-analysis. Int J Cardiol 2018; 269: 292-7.
[http://dx.doi.org/10.1016/j.ijcard.2018.07.009] [PMID: 30045826]
[63]
Basili S, Raparelli V, Vestri A, Di Tanna GL, Violi F. Comparison of efficacy of antiplatelet treatments for patients with claudication. A meta-analysis. Thromb Haemost 2010; 103(4): 766-73.
[http://dx.doi.org/10.1160/TH09-09-0635] [PMID: 20174763]
[64]
Katsanos K, Spiliopoulos S, Saha P, et al. Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis. PLoS One 2015; 10(8): e0135692.
[http://dx.doi.org/10.1371/journal.pone.0135692] [PMID: 26274912]
[65]
Bonaca MP, Nault P, Giugliano RP, et al. Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation 2018; 137(4): 338-50.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032235] [PMID: 29133605]
[66]
Jukema JW, Szarek M, Zijlstra LE, et al. ODYSSEY OUTCOMES Committees and Investigators. Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES Trial. J Am Coll Cardiol 2019; 74(9): 1167-76.
[http://dx.doi.org/10.1016/j.jacc.2019.03.013] [PMID: 30898609]
[67]
Verma S, Mazer CD, Al-Omran M, et al. Cardiovascular Outcomes and Safety of Empagliflozin in Patients With Type 2 Diabetes Mellitus and Peripheral Artery Disease: A Subanalysis of EMPA-REG OUTCOME. Circulation 2018; 137(4): 405-7.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032031] [PMID: 29133602]
[68]
Savarese G, Reiner MF, Uijl A, et al. Antithrombotic therapy and major adverse limb events in patients with chronic lower extremity arterial disease: systematic review and meta-analysis from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy in Collaboration with the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases. Eur Heart J Cardiovasc Pharmacother 2020; 6(2): 86-93.
[PMID: 31392312]

© 2022 Bentham Science Publishers | Privacy Policy