Antithrombotische Therapie der peripheren arteriellen Verschlusskrankheit – ein Überblick über aktuelle Evidenz, Praxis und Ausblick

Zusammenfassung

Die periphere arterielle Verschlusskrankheit ist eine häufige, chronische Störung der arteriellen Durchblutung v. a. der unteren Extremitäten, wobei fibröse Plaques der Gefäßwand zu Stenosen und Thrombenbildung führen. Bei betroffenen Patienten besteht ein hohes Risiko für kardiovaskuläre Komplikationen im gesamten arteriellen Gefäßsystem, auch nach dortigen Eingriffen. Daher besteht Optimierungsbedarf bei der antithrombotischen Therapie. Zur Mehrfach-Thrombozytenaggregationshemmung durch neue Arzneimittelklassen werden in den nächsten Jahren Studiendaten erwartet. Aktuelle Studien zeigten bei Hemmung der Gerinnungskaskade durch direkte orale Antikoagulanzien klinische Vorteile bei vertretbarem Sicherheitsprofil. Grundlage medikamentöser Therapie bleibt das Management von Risikofaktoren wie Übergewicht und Nikotin sowie die Korrektur metabolischer Störungen. Diese Aspekte sollten den behandelnden Ärzten bekannt sein, um eine optimale Versorgung und Motivation der Patienten zu erreichen.

Abstract

Peripheral arterial occlusive disease is a frequent and chronic vascular disorder mostly affecting the lower limbs and caused by fibrous plaques in arteries that can result in stenoses and thrombi. Patients suffering from this condition show a high risk for cardiovascular complications of the complete arterial vascular system, especially post-procedural. Thus, there is a need to optimize anti-thrombotic therapy. Data on multiple antiplatelet aggregation therapy including new drug classes are expected in the coming years. In addition, recent studies showed that direct oral anticoagulation provided clinical advantages combined with a reasonable safety profile. Management of risk factors such as overweight and nicotine and correction of metabolic disorders are not to be ignored and the background to further therapy. All treating physicians should be aware of these aspects to guarantee an optimal care and motivation of their patients.

Schlüsselwörter

PAVK - Atherosklerose - Risikomanagement - Thrombozytenaggregationshemmer - Antikoagulanzien

Key words

PAD - arteriosclerosis - risk management - antiplatelet therapy - anticoagulation

• Literatur

• 1 Jones WS, Patel MR. Antithrombotic Therapy in Peripheral Artery Disease: Generating and Translating Evidence Into Practice. J Am Coll Cardiol 2018; 71: 352-362
• 2 Duvall WL, Vorchheimer DA. Multi-bed vascular disease and atherothrombosis: scope of the problem. J Thromb Thrombolysis 2004; 17: 51-61
• 3 Lawall H, Diehm C, Hoffmann U. et al. Update PAVK: Epidemiology, comorbidity and prognosis of peripheral arterial obstructive disease. Dtsch med Wochenschr 2015; 140: 1798-1802
• 4 Noronen K, Saarinen E, Albäck A. et al. Analysis of the Elective Treatment Process for Critical Limb Ischaemia with Tissue Loss: Diabetic Patients Require Rapid Revascularisation. Eur J Vasc Endovasc Surg 2017; 53: 206-213
• 5 Alahdab F, Wang AT, Elraiyah TA. et al. A systematic review for the screening for peripheral arterial disease in asymptomatic patients. J Vasc Surg 2015; 61: 42S-53S
• 6 Dohmen A, Espinola-Klein C, Huppert P. et al. S3-Leitlinie PAVK. Diagnostik, Therapie und Nachsorge der peripheren arteriellen Verschlusskrankheit. S3-Leitlinie AWMF 065 – 003. VASA 2016; 45: 1-96
• 7 De Backer TL, Vander Stichele R, Lehert P. et al. Naftidrofuryl for intermittent claudication. Cochrane Database Sys Rev 2008; 2: CD001368
• 8 Bedenis R, Stewart M, Cleanthis M. et al. Cilostazol for intermittent claudication. Cochrane Database Syst Rev 2014; 10: CD003748
• 9 Bendermacher BL, Willigendael EM, Teijink JA. et al. Medical management of peripheral arterial disease. J Thromb Haem 2005; 3: 1628-1637
• 10 Zhang Y, Hu G, Yuan Z. et al. Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis. PloS one 2012; 7: e42551
• 11 Espinola-Klein C. Anti-Thrombotic Treatment of Patients with Peripheral Artery Disease (PAD). Dtsch Med Wochenschr 2018; 143: 1060-1064 . doi:10.1055/a-0507-5565
• 12 CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348: 1329-1339
• 13 Creager MA. Results of the CAPRIE trial: efficacy and safety of clopidogrel. Vascular Medicine 1998; 3: 257-260
• 14 Morrow DA, Braunwald E, Bonaca MP. et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366: 1404-1413
• 15 Bonaca MP, Scirica BM, Creager MA. et al. Vorapaxar in patients with peripheral artery disease: results from TRA2°P-TIMI 50. Circulation 2013; 127: 1522-1529, 1529e1–6
• 16 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: 2157-2164
• 17 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: 1998-2006
• 18 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: 699-706
• 19 Fowkes FG, Price JF, Stewart MC. et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA 2010; 303: 841-848
• 20 Belch J, MacCuish A, Campbell I. et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008; 337: a1840
• 21 Soejima H, Morimoto T, Saito Y. et al. Aspirin for the primary prevention of cardiovascular events in patients with peripheral artery disease or diabetes mellitus. Analyses from the JPAD, POPADAD and AAA trials. Thromb Haem 2010; 104: 1085-1088
• 22 Bonaca MP, Bhatt DL, Cohen M. et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791-800
• 23 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: 2719-2728
• 24 Jones WS, Baumgartner I, Hiatt WR. et al. Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease. Circulation 2017; 135: 241-250
• 25 Moll F, Baumgartner I, Jaff M. et al. 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: 158-168
• 26 Eikelboom JW, Connolly SJ, Bosch J. et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med 2017; 377: 1319-1330
• 27 Anand SS, Bosch J, Eikelboom JW. et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet 2017;
• 28 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: 2306-2315
• 29 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). 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). European Heart Journal 2018; 39: 763-821
• 30 Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Brit Med J 2002; 324: 71-86
• 31 Sobel M, Verhaeghe R. Antithrombotic Therapy for Peripheral Artery Occlusive Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (06) 815-843
• 32 Bhatt DL, Fox KA, Hacke W. et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Eng J Med 2006; 354: 1706-1717
• 33 Capell WH, Bonaca MP, Nehler MR. et al. Rationale and design for the Vascular Outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD). Am Heart J 2018; 199: 83-91
• 34 Behrendt CA, Härter M, Kriston L. et al. IDOMENEO – Ist die Versorgungsrealität in der Gefäßmedizin Leitlinien- und Versorgungsgerecht? Ein Projekt zur Qualitätsentwicklung am Beispiel der peripheren arteriellen Verschlusskrankheit. Gefässchirurgie 2017; 22: 41-47
• 35 Malyar N, Freisinger E, Reinecke H. Periphere arterielle Verschlusskrankheit – Entwicklungen zur Morbidität und Letalität in Deutschland. Dtsch Med Wochenschr 2018; 143: 766-770