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2022 | Embolieprophylaxe und Antikoagulation | OriginalPaper | Buchkapitel

9. Antithrombotische Therapie

verfasst von : Dr. med. Hans Wille

Erschienen in: Arzneiverordnungs-Report 2022

Verlag: Springer Berlin Heidelberg

Zusammenfassung

Auf einen Blick

Trend Die Gesamtverordnungen der Thrombozytenaggregationshemmer sind 2021 gegenüber dem Vorjahr minimal gesunken, die der oralen Antikoagulantien weiter angestiegen, wenn auch geringer als im Vorjahr. Die Verordnungen der Vitamin-K-Antagonisten nahmen auch 2021 weiter deutlich ab, während die der Thrombin- und Faktor Xa-Antagonisten gegenüber 2020 erneut deutlich zugenommen haben. Der Verordnungsanteil der Vitamin-K-Antagonisten an allen oralen Antikoagulantien beträgt jetzt nur noch 16,8 %. Die Kosten aller Antithrombotika sind 2021 auf 3.004 Mio. € gestiegen. Der Anstieg gegenüber 2020 um 6,2 % ist auch diesmal allein durch die neuen direkten oralen Antikoagulantien bedingt. Bei den Antihämorrhagika sind die Faktor-VIII-Präparate die umsatzstärkste Gruppe. Modifizierte rekombinante Gerinnungsfaktoren sowie ein monoklonaler Antikörper (Emicizumab) als Faktor VIIIa-Mimetikum erweitern die Therapieoptionen bei Patienten mit angeborener Hämophilie A oder B.
Bewertung Acetylsalicylsäure ist weiter der wichtigste Thrombozytenaggregationshemmer. ADP-Rezeptorantagonisten haben allein oder in Kombination mit Acetylsalicylsäure nur in bestimmten kardiovaskulären Spezialindikationen einen nachgewiesenen Zusatznutzen. Ticagrelor und möglicherweise auch Prasugrel zeigen bei einzelnen Patientengruppen mit akutem Koronarsyndrom Vorteile gegenüber Clopidogrel. Die direkt wirkenden oder auch neuen Antikoagulantien reduzieren das Risiko ischämischer Schlaganfälle bei Vorhofflimmern ähnlich wie Vitamin K-Antagonisten, lösen aber weniger Hirnblutungen aus. Validierte, in der Praxis verfügbare Labortests existieren für die neuen oralen Antikoagulantien bisher nicht. Vitamin-K-Antagonisten werden in Leitlinien zwar weiterhin zur Thromboembolieprophylaxe bei Patienten mit nichtvalvulärem Vorhofflimmern empfohlen, inzwischen jedoch meist nachrangig zu den neuen oralen Antikoagulantien. Dennoch sind sie für viele Patienten weiterhin als Therapieoption anzusehen, vor allem für Patienten nach Klappenersatz mit einer Indikation für eine Antikoagulation. Die Verordnungszahlen der neuen oralen Antikoagulantien stiegen seit 2012 nahezu linear an, zeigen jetzt aber eine gewisse Abflachung. Sie sind bis zu 20-fach teurer und haben allein 2021 Kosten von 2,485 Mrd. € verursacht.
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Zurück zum Zitat Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver LP, Rinaldi MJ, Massaro JM, DAPT Study Investigators (2014) Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 371:2155–2166PubMedPubMedCentral Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver LP, Rinaldi MJ, Massaro JM, DAPT Study Investigators (2014) Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 371:2155–2166PubMedPubMedCentral
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Zurück zum Zitat Mismetti P, Laporte S, Darmon J-Y, Buchmüller A, Decousus H (2001) Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 88:913–930PubMed Mismetti P, Laporte S, Darmon J-Y, Buchmüller A, Decousus H (2001) Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 88:913–930PubMed
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Zurück zum Zitat National Institute for Health and Care Excellence (2021) Atrial fibrillation: diagnosis and management. Published: 27 April 2021. NICE clinical guideline 196. guidance.nice.org.uk/cg196 National Institute for Health and Care Excellence (2021) Atrial fibrillation: diagnosis and management. Published: 27 April 2021. NICE clinical guideline 196. guidance.nice.org.uk/cg196
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Zurück zum Zitat Park SJ, Park DW, Kim YH, Kang SJ, Lee SW, Lee CW, Han KH, Park SW, Yun SC, Lee SG, Rha SW, Seong IW, Jeong MH, Hur SH, Lee NH, Yoon J, Yang JY, Lee BK, Choi YJ, Chung WS, Lim DS, Cheong SS, Kim KS, Chae JK, Nah DY, Jeon DS, Seung KB, Jang JS, Park HS, Lee K (2010) Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 362:1374–1382PubMed Park SJ, Park DW, Kim YH, Kang SJ, Lee SW, Lee CW, Han KH, Park SW, Yun SC, Lee SG, Rha SW, Seong IW, Jeong MH, Hur SH, Lee NH, Yoon J, Yang JY, Lee BK, Choi YJ, Chung WS, Lim DS, Cheong SS, Kim KS, Chae JK, Nah DY, Jeon DS, Seung KB, Jang JS, Park HS, Lee K (2010) Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 362:1374–1382PubMed
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Zurück zum Zitat PEGASUS-TIMI 54 Steering Committee and Investigators, Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS (2015) Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 372:1791–1800 PEGASUS-TIMI 54 Steering Committee and Investigators, Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS (2015) Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 372:1791–1800
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Zurück zum Zitat RE-DUAL PCI Steering Committee and Investigators, Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH (2017) Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 377:1513–1524 RE-DUAL PCI Steering Committee and Investigators, Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH (2017) Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 377:1513–1524
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Zurück zum Zitat Stevens SM, Woller SC, Baumann Kreuziger L, Bounameaux H, Doerschug K, Geersing GJ, Huisman MV, Kearon C, King CS, Knighton AJ, Lake E, Murin S, Vintch JRE, Wells PS, Moores LK (2021) Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest 160:e545–e608PubMed Stevens SM, Woller SC, Baumann Kreuziger L, Bounameaux H, Doerschug K, Geersing GJ, Huisman MV, Kearon C, King CS, Knighton AJ, Lake E, Murin S, Vintch JRE, Wells PS, Moores LK (2021) Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest 160:e545–e608PubMed
Zurück zum Zitat Svendsen JH, Diederichsen SZ, Højberg S, Krieger DW, Graff C, Kronborg C, Olesen MS, Nielsen JB, Holst AG, Brandes A, Haugan KJ, Køber L (2021) Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial. Lancet 398:1507–1516PubMed Svendsen JH, Diederichsen SZ, Højberg S, Krieger DW, Graff C, Kronborg C, Olesen MS, Nielsen JB, Holst AG, Brandes A, Haugan KJ, Køber L (2021) Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial. Lancet 398:1507–1516PubMed
Zurück zum Zitat Svennberg E, Friberg L, Frykman V, Al-Khalili F, Engdahl J, Rosenqvist M (2021) Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP): a multicentre, parallel group, unmasked, randomised controlled trial. Lancet 398:1498–1506PubMed Svennberg E, Friberg L, Frykman V, Al-Khalili F, Engdahl J, Rosenqvist M (2021) Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP): a multicentre, parallel group, unmasked, randomised controlled trial. Lancet 398:1498–1506PubMed
Zurück zum Zitat The ACTIVE Investigators (2009) Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 360:2066–2078 The ACTIVE Investigators (2009) Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 360:2066–2078
Zurück zum Zitat The ACTIVE Writing Group of the ACTIVE Investigators (2006) Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 367:1903–1912 The ACTIVE Writing Group of the ACTIVE Investigators (2006) Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 367:1903–1912
Zurück zum Zitat The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345:494–502 The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345:494–502
Zurück zum Zitat The EINSTEIN Investigators (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510 The EINSTEIN Investigators (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510
Zurück zum Zitat The EINSTEIN-PE Investigators (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297 The EINSTEIN-PE Investigators (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297
Zurück zum Zitat The Hokusai-VTE Investigators (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415 The Hokusai-VTE Investigators (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415
Zurück zum Zitat The Warfarin Antiplatelet Vascular Evaluation Trial Investigators (2007) Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 357:217–227 The Warfarin Antiplatelet Vascular Evaluation Trial Investigators (2007) Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 357:217–227
Zurück zum Zitat Ujeyl M, Köster I, Wille H, Stammschulte T, Hein R, Harder S, Gundert-Remy U, Bleek J, Ihle P, Schröder H, Schillinger G, Zawinell A, Schubert I (2018) Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation. Eur J Clin Pharmacol 74:1317–1325PubMed Ujeyl M, Köster I, Wille H, Stammschulte T, Hein R, Harder S, Gundert-Remy U, Bleek J, Ihle P, Schröder H, Schillinger G, Zawinell A, Schubert I (2018) Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation. Eur J Clin Pharmacol 74:1317–1325PubMed
Zurück zum Zitat U.S. Preventive Services Task Force (2022) Screening for atrial fibrillation – US preventive services task force recommendation statement. JAMA 327:360–367 U.S. Preventive Services Task Force (2022) Screening for atrial fibrillation – US preventive services task force recommendation statement. JAMA 327:360–367
Zurück zum Zitat Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN, ESC Scientific Document Group, ESC Committee for Practice Guidelines (CPG), ESC National Cardiac Societies (2018) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 39:213–260PubMed Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN, ESC Scientific Document Group, ESC Committee for Practice Guidelines (CPG), ESC National Cardiac Societies (2018) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 39:213–260PubMed
Zurück zum Zitat Valgimigli M, Gragnano F, Branca M, Franzone A, Baber U, Jang Y, Kimura T, Hahn JY, Zhao Q, Windecker S, Gibson CM, Kim BK, Watanabe H, Song YB, Zhu Y, Vranckx P, Mehta S, Hong SJ, Ando K, Gwon HC, Serruys PW, Dangas GD, McFadden EP, Angiolillo DJ, Heg D, Jüni P, Mehran R (2021) P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials. BMJ 373:n1332. https://doi.org/10.1136/bmj.n1332 CrossRefPubMedPubMedCentral Valgimigli M, Gragnano F, Branca M, Franzone A, Baber U, Jang Y, Kimura T, Hahn JY, Zhao Q, Windecker S, Gibson CM, Kim BK, Watanabe H, Song YB, Zhu Y, Vranckx P, Mehta S, Hong SJ, Ando K, Gwon HC, Serruys PW, Dangas GD, McFadden EP, Angiolillo DJ, Heg D, Jüni P, Mehran R (2021) P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials. BMJ 373:n1332. https://​doi.​org/​10.​1136/​bmj.​n1332 CrossRefPubMedPubMedCentral
Zurück zum Zitat Verdoia M, Schaffer A, Barbieri L, Suryapranata H, De Luca G (2016) Bivalirudin versus unfractionated heparin in acute coronary syndromes: an updated meta-analysis of randomized trials. Rev Esp Cardiol (Engl Ed) 69:732–745PubMed Verdoia M, Schaffer A, Barbieri L, Suryapranata H, De Luca G (2016) Bivalirudin versus unfractionated heparin in acute coronary syndromes: an updated meta-analysis of randomized trials. Rev Esp Cardiol (Engl Ed) 69:732–745PubMed
Zurück zum Zitat Vranckx P, Valgimigli M, Eckardt L, Tijssen J, Lewalter T, Gargiulo G, Batushkin V, Campo G, Lysak Z, Vakaliuk I, Milewski K, Laeis P, Reimitz PE, Smolnik R, Zierhut W, Goette A (2019) Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet 394:1335–1343PubMed Vranckx P, Valgimigli M, Eckardt L, Tijssen J, Lewalter T, Gargiulo G, Batushkin V, Campo G, Lysak Z, Vakaliuk I, Milewski K, Laeis P, Reimitz PE, Smolnik R, Zierhut W, Goette A (2019) Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet 394:1335–1343PubMed
Zurück zum Zitat Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Thorsén M, PLATO Investigators (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057PubMed Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Thorsén M, PLATO Investigators (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057PubMed
Zurück zum Zitat Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, Pais P, Dans A, Eikelboom J, Oldgren J, Pogue J, Reilly PA, Yang S, Connolly SJ, RE-LY investigators (2010) Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 376:975–983PubMed Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, Pais P, Dans A, Eikelboom J, Oldgren J, Pogue J, Reilly PA, Yang S, Connolly SJ, RE-LY investigators (2010) Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 376:975–983PubMed
Zurück zum Zitat Wallentin L, Lopes RD, Hanna M, Thomas L, Hellkamp A, Nepal S, Hylek EM, Al-Khatib SM, Alexander JH, Alings M, Amerena J, Ansell J, Aylward P, Bartunek J, Commerford P, De Caterina R, Erol C, Harjola VP, Held C, Horowitz JD, Huber K, Husted S, Keltai M, Lanas F, Lisheng L, McMurray JJ, Oh BH, Rosenqvist M, Ruzyllo W, Steg PG, Vinereanu D, Xavier D, Granger CB, Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Investigators (2013) Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation 127:2166–2176PubMed Wallentin L, Lopes RD, Hanna M, Thomas L, Hellkamp A, Nepal S, Hylek EM, Al-Khatib SM, Alexander JH, Alings M, Amerena J, Ansell J, Aylward P, Bartunek J, Commerford P, De Caterina R, Erol C, Harjola VP, Held C, Horowitz JD, Huber K, Husted S, Keltai M, Lanas F, Lisheng L, McMurray JJ, Oh BH, Rosenqvist M, Ruzyllo W, Steg PG, Vinereanu D, Xavier D, Granger CB, Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Investigators (2013) Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation 127:2166–2176PubMed
Zurück zum Zitat White RH, Ginsberg JS (2003) Low-molecular-weight heparins: are they all the same? Br J Hematol 121:12–20 White RH, Ginsberg JS (2003) Low-molecular-weight heparins: are they all the same? Br J Hematol 121:12–20
Zurück zum Zitat Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM, TRITON-TIMI 38 Investigators (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015PubMed Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM, TRITON-TIMI 38 Investigators (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015PubMed
Zurück zum Zitat Yao X, Abraham NS, Alexander GC, Crown W, Montori VM, Sangaralingham LR, Gersh BJ, Shah ND, Noseworthy PA (2016) Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc 5:e3074 Yao X, Abraham NS, Alexander GC, Crown W, Montori VM, Sangaralingham LR, Gersh BJ, Shah ND, Noseworthy PA (2016) Effect of adherence to oral anticoagulants on risk of stroke and major bleeding among patients with atrial fibrillation. J Am Heart Assoc 5:e3074
Zurück zum Zitat Yin SH, Xu P, Wang B, Lu Y, Wu QY, Zhou ML, Wu JR, Cai JJ, Sun X, Yuan H (2019) Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis. BMJ 365:l2222PubMedPubMedCentral Yin SH, Xu P, Wang B, Lu Y, Wu QY, Zhou ML, Wu JR, Cai JJ, Sun X, Yuan H (2019) Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis. BMJ 365:l2222PubMedPubMedCentral
Metadaten
Titel
Antithrombotische Therapie
verfasst von
Dr. med. Hans Wille
Copyright-Jahr
2022
Verlag
Springer Berlin Heidelberg
DOI
https://doi.org/10.1007/978-3-662-66303-5_9

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