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Anticoagulant plus antiplatelet therapy for atrial fibrillation

Cost–utility of combination therapy with non-vitamin K oral anticoagulants vs. warfarin

Antikoagulation plus Thrombozytenaggregationshemmung bei Vorhofflimmern

Kosten-Nutzwert-Vergleich zwischen Nicht-Vitamin-K-abhängigen oralen Antikoagulanzien und Warfarin

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Abstract

Background

Emerging evidence indicates combination therapy with anticoagulants and antiplatelet agents for atrial fibrillation (AF) will be increasingly required. Numerous studies compare the efficacy and cost-effectiveness of anticoagulation alone in AF, i. e., non-vitamin K oral anticoagulants (NOACs) vs. warfarin. However, the addition of antiplatelet agents with their potential for decreasing thromboembolic stroke counter-balanced by an increased bleeding risk has received less attention. Thus, we evaluated the cost–utility of this combination therapy.

Method and results

We obtained event estimates from our recent meta-analysis of four randomized clinical trials designed to compare NOACs with warfarin in patients with AF. We examined patient subgroups within each trial that received antiplatelet therapy in addition to anticoagulation. Utilities were derived from the literature and cost estimates from the German health-care system. A decision tree was constructed and populated with these parameters. We used a 1-year time horizon because combination therapy is not recommended beyond this time. We calculated the incremental cost–effectiveness ratio (ICER) per quality-adjusted life-year (QALY). The derived ICER was 13,168.50 € per QALY. NOAC prices exerted considerable influence on the calculation. Nevertheless, there is potential for ICER shifts in favor of warfarin, e.g., if warfarin-mediated anticoagulation control is improved and thereby adverse events decrease. Conversely, if NOAC adherence decreases, adverse events could increase.

Conclusion

The derived ICER was 13,168.50 € per QALY, consistent with NOACs being cost-effective vs. warfarin when anticoagulation is used with antiplatelet agents.

Nevertheless, country-, practice-, and patient-related factors influence the ICER. Our cost–utility calculation should be used a starting point for decision-making.

Zusammenfassung

Hintergrund

Aktueller Evidenz zufolge ist die Kombinationstherapie aus Antikoagulanzien und Thrombozytenaggregationshemmern bei Vorhofflimmern (VHF) häufig und zunehmend. In zahlreichen Studien wird nur die Wirksamkeit und Wirtschaftlichkeit zwischen Nicht-Vitamin-K-abhängigen oralen Antikoagulanzien (NOAK) und Warfarin verglichen. Die Aufmerksamkeit richtet sich jedoch weniger auf die zusätzliche Gabe von Thrombozytenaggregationshemmern mit ihrem Potenzial eines verminderten Risikos für thromboembolisch bedingte Schlaganfälle bei gleichzeitig erhöhtem Blutungsrisiko. Daher untersuchten die Autoren das Kosten-Nutzen-Verhältnis dieser Kombinationstherapie.

Methoden und Ergebnisse

Aus der aktuellen Metaanalyse von 4 randomisierten klinischen Studien zum Vergleich von NOAK mit Warfarin bei VHF-Patienten wurden Ereignisschätzwerte der Patientensubgruppen mit zusätzlicher Thrombozytenaggregationshemmung ermittelt. Die Nutzwerte („utilities“) wurden der Literatur entnommen, die Kostenschätzwerte aus Daten des deutschen Gesundheitssystems. Ein Entscheidungsbaum wurde entwickelt und mit diesen Parametern bestückt. Die Autoren benutzten einen Ein-Jahres-Horizont, da die Kombinationstherapie darüber hinaus nicht empfohlen wird. Es wurde das inkrementelle Kosten-Effektivitäts-Verhältnis (ICER) pro qualitätskorrigiertem Lebensjahr („quality-adjusted life-year“, QALY) berechnet. Der ermittelte ICER-Wert betrug 13.168,50 € pro QALY. Die Preise für NOAKs beeinflussen den ICER beträchtlich. Trotzdem besteht ein Potenzial für Verschiebungen des ICERs zugunsten von Warfarin, z. B., wenn die Steuerung der Antikoagulation mittels Warfarin verbessert würde und somit weniger Komplikationen darunter aufträten bzw. wenn unter verminderter Compliance der NOAK-Therapie mehr Komplikationen aufträten.

Schlussfolgerung

Für die Kombinationstherapie eines Thrombozytenaggregationshemmers mit einem NOAK wurde ein ICER von 13.168,50 € pro QALY ermittelt, was als kosteneffizient angesehen werden kann, auch wenn in Deutschland keine festen Grenzwerte hierfür existieren. Dennoch beeinflussen landes-, praxis- und patientenbezogene Faktoren den ICER-Wert. Die vorliegende Kosten-Nutzwert-Berechnung sollte als Startpunkt für Entscheidungsfindungen dienen.

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References

  1. Almutairi AR, Zhou L, Gellad WF, Lee JK, Slack MK, Martin JR, Lo-Ciganic WH (2017) Effectiveness and safety of non-vitamin K antagonist oral anticoagulants for atrial fibrillation and venous thromboembolism: a systematic review and meta-analyses. Clin Ther 39(7):1456–1478 e1436. https://doi.org/10.1016/j.clinthera.2017.05.358

    Article  CAS  PubMed  Google Scholar 

  2. Capodanno D, Capranzano P, Giacchi G, Calvi V, Tamburino C (2013) Novel oral anticoagulants versus warfarin in non-valvular atrial fibrillation: a meta-analysis of 50,578 patients. Int J Cardiol 167(4):1237–1241. https://doi.org/10.1016/j.ijcard.2012.03.148

    Article  PubMed  Google Scholar 

  3. Coyle D, Coyle K, Cameron C, Lee K, Kelly S, Steiner S, Wells GA (2013) Cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation. Value Health 16(4):498–506. https://doi.org/10.1016/j.jval.2013.01.009

    Article  PubMed  Google Scholar 

  4. Freeman JV, Zhu RP, Owens DK, Garber AM, Hutton DW, Go AS, Wang PJ, Turakhia MP (2011) Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med 154(1):1–11. https://doi.org/10.7326/0003-4819-154-1-201101040-00289

    Article  PubMed  Google Scholar 

  5. Hicks T, Stewart F, Eisinga A (2016) NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis. Open Heart 3(1):e279. https://doi.org/10.1136/openhrt-2015-000279

    Article  PubMed  PubMed Central  Google Scholar 

  6. You JH (2014) Novel oral anticoagulants versus warfarin therapy at various levels of anticoagulation control in atrial fibrillation—a cost-effectiveness analysis. J Gen Intern Med 29(3):438–446. https://doi.org/10.1007/s11606-013-2639-2

    Article  PubMed  Google Scholar 

  7. Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN (2018) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J 39(3):213–260. https://doi.org/10.1093/eurheartj/ehx419 (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))

    Article  PubMed  Google Scholar 

  8. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, Committee R‑LS, Investigators (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151. https://doi.org/10.1056/NEJMoa0905561

    Article  CAS  PubMed  Google Scholar 

  9. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM, Investigators RA (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891. https://doi.org/10.1056/NEJMoa1009638

    Article  CAS  PubMed  Google Scholar 

  10. Secemsky EA, Butala NM, Kartoun U, Mahmood S, Wasfy JH, Kennedy KF, Shaw SY, Yeh RW (2016) Use of chronic oral anticoagulation and associated outcomes among patients undergoing percutaneous coronary intervention. J Am Heart Assoc. https://doi.org/10.1161/JAHA.116.004310

    Article  PubMed  PubMed Central  Google Scholar 

  11. Barnes GD, Lucas E, Alexander GC, Goldberger ZD (2015) National trends in ambulatory oral anticoagulant use. Am J Med 128(12):1300–1305 e1302. https://doi.org/10.1016/j.amjmed.2015.05.044

    Article  PubMed  PubMed Central  Google Scholar 

  12. Go AS, Hylek EM, Phillips KA, Chang YC, Henault LE, Selby JV, Singer DE (2001) Prevalence of diagnosed atrial fibrillation in adults—National implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. JAMA 285(18):2370–2375. https://doi.org/10.1001/jama.285.18.2370

    Article  CAS  PubMed  Google Scholar 

  13. Kapadia S (2017) Trends in cardiovascular risk profiles. Cleve Clin J Med 84(12 Suppl 4):e6–e9. https://doi.org/10.3949/ccjm.84.s4.02

    Article  PubMed  Google Scholar 

  14. Bennaghmouch N, de Veer A, Bode K, Mahmoodi BK, Dewilde WJM, Lip GYH, Brueckmann M, Kleine E, Ten Berg JM (2017) The efficacy and safety of the use of non-vitamin-K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation and concomitant aspirin therapy: a meta-analysis of randomized trials. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.117.028513

    Article  PubMed  Google Scholar 

  15. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L, Committees A, Investigators (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981–992. https://doi.org/10.1056/NEJMoa1107039

    Article  CAS  PubMed  Google Scholar 

  16. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM, Investigators EA-T (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369(22):2093–2104. https://doi.org/10.1056/NEJMoa1310907

    Article  CAS  PubMed  Google Scholar 

  17. Gage BF, Cardinalli AB, Owens DK (1996) The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med 156(16):1829–1836

    Article  CAS  PubMed  Google Scholar 

  18. Sullivan PW, Slejko JF, Sculpher MJ, Ghushchyan V (2011) Catalogue of EQ-5D scores for the United Kingdom. Med Decis Making 31(6):800–804. https://doi.org/10.1177/0272989x11401031

    Article  PubMed  Google Scholar 

  19. Krejczy M, Harenberg J, Wehling M, Obermann K, Lip GYH (2015) Cost-effectiveness of anticoagulation in patients with nonvalvular atrial fibrillation with Edoxaban compared to Warfarin in Germany. Biomed Res Int. https://doi.org/10.1155/2015/876923

    Article  PubMed  PubMed Central  Google Scholar 

  20. online RL (2017) Arzneimittelinformation für Deutschland. http://online.rote-liste.de/. Accessed 1 Sept 2017

    Google Scholar 

  21. Bundesvereinigung K (2017) EBM Einheitlicher Bewertungsmaßstab. http://www.kbv.de/html/online-ebm.php. Accessed 1 Sept 2017

    Google Scholar 

  22. GmbH I (2017) Fallpauschalen-Katalog 2017. http://www.g-drg.de/cms/G-DRG-System_2016/Fallpauschalen-Katalog. Accessed 1 Sept 2016

    Google Scholar 

  23. Stevanovic J, Pompen M, Le HH, Rozenbaum MH, Tieleman RG, Postma MJ (2014) Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands. PLoS ONE 9(8):e103974. https://doi.org/10.1371/journal.pone.0103974

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sullivan PW, Arant TW, Ellis SL, Ulrich H (2006) The cost effectiveness of anticoagulation management services for patients with atrial fibrillation and at high risk of stroke in the US. Pharmacoeconomics 24(10):1021–1033

    Article  PubMed  Google Scholar 

  25. Berg J, Lindgren P, Nieuwlaat R, Bouin O, Crijns H (2010) Factors determining utility measured with the EQ-5D in patients with atrial fibrillation. Qual Life Res 19(3):381–390. https://doi.org/10.1007/s11136-010-9591-y

    Article  PubMed  Google Scholar 

  26. Wynn GJ, Todd DM, Webber M, Bonnett L, McShane J, Kirchhof P, Gupta D (2014) The European Heart Rhythm Association symptom classification for atrial fibrillation: validation and improvement through a simple modification. Europace 16(7):965–972. https://doi.org/10.1093/europace/eut395

    Article  PubMed  PubMed Central  Google Scholar 

  27. Vandoros S, Kanavos P (2013) The generics paradox revisited: empirical evidence from regulated markets. Appl Econ 45:3230–3239

    Article  Google Scholar 

  28. Costa-Fonta J, Rudisilla C, Ta S (2014) Brand loyalty, patients and limited generic medicines uptake. Health Policy (New York) 116:224–233. https://doi.org/10.1016/j.healthpol.2014.01.015

    Article  Google Scholar 

  29. Gonzalez J, Sismeiro C, Dutta S, Stern P (2008) Can branded drugs benefit from generic entry? The role of detailing and price in switching to non-bioequivalent molecules. Int J Res Mark 25:247–260. https://doi.org/10.1016/j.ijresmar.2008.08.002

    Article  Google Scholar 

  30. Vandoros S (2014) Therapeutic substitution post-patent expiry: the cases of ACE-inhibitor and proton pump inhibitors. Health Econ 23:621–630. https://doi.org/10.1002/hec.2935

    Article  PubMed  Google Scholar 

  31. Kanavos P, Vandoros S (2011) Determinants of branded prescription medicine prices in OECD countries. Health Econ Policy Law 6:337–367. https://doi.org/10.1017/S1744133111000090

    Article  PubMed  Google Scholar 

  32. Dylst P, Simoens S (2011) Does the market share of generic medicines influence the price level? A European analysis. Pharmacoeconomics 10:875–882

    Article  Google Scholar 

  33. Dylst P, Simoens S (2010) Generic medicine pricing policies in Europe: current status and impact. Pharmaceuticals (Basel) 3:471–481. https://doi.org/10.3390/ph3030471

    Article  Google Scholar 

  34. Morgan CL, McEwan P, Tukiendorf A, Robinson PA, Clemens A, Plumb JM (2009) Warfarin treatment in patients with atrial fibrillation: observing outcomes associated with varying levels of INR control. Thromb Res 124(1):37–41. https://doi.org/10.1016/j.thromres.2008.09.016

    Article  CAS  PubMed  Google Scholar 

  35. Nieuwlaat R, Connolly BJ, Hubers LM, Cuddy SM, Eikelboom JW, Yusuf S, Connolly SJ, Investigators A (2012) Quality of individual INR control and the risk of stroke and bleeding events in atrial fibrillation patients: a nested case control analysis of the ACTIVE W study. Thromb Res 129(6):715–719. https://doi.org/10.1016/j.thromres.2011.08.024

    Article  CAS  PubMed  Google Scholar 

  36. Baker WL, Cios DA, Sander SD, Coleman CI (2009) Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm 15(3):244–252. https://doi.org/10.18553/jmcp.2009.15.3.244

    Article  PubMed  Google Scholar 

  37. Cotte FE, Benhaddi H, Duprat-Lomon I, Doble A, Marchant N, Letierce A, Huguet M (2014) Vitamin K antagonist treatment in patients with atrial fibrillation and time in therapeutic range in four European countries. Clin Ther 36(9):1160–1168. https://doi.org/10.1016/j.clinthera.2014.07.016

    Article  CAS  PubMed  Google Scholar 

  38. Piccini JP, Hellkamp AS, Lokhnygina Y, Patel MR, Harrell FE, Singer DE, Becker RC, Breithardt G, Halperin JL, Hankey GJ, Berkowitz SD, Nessel CC, Mahaffey KW, Fox KA, Califf RM, Investigators RA (2014) Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial. J Am Heart Assoc 3(2):e521. https://doi.org/10.1161/JAHA.113.000521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 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(22):2166–2176. https://doi.org/10.1161/CIRCULATIONAHA.112.142158

    Article  CAS  PubMed  Google Scholar 

  40. 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, Investigators R‑L (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(9745):975–983. https://doi.org/10.1016/S0140-6736(10)61194-4

    Article  CAS  PubMed  Google Scholar 

  41. Brown JD, Shewale AR, Talbert JC (2016) Adherence to Rivaroxaban, Dabigatran, and Apixaban for stroke prevention in incident, treatment-naive nonvalvular atrial fibrillation. J Manag Care Spec Pharm 22(11):1319–1329. https://doi.org/10.18553/jmcp.2016.22.11.1319

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lader E, Martin N, Cohen G, Meyer M, Reiter P, Dimova A, Parikh D (2012) Warfarin therapeutic monitoring: is 70 % time in the therapeutic range the best we can do? J Clin Pharm Ther 37(4):375–377. https://doi.org/10.1111/j.1365-2710.2011.01324.x

    Article  CAS  PubMed  Google Scholar 

  43. Martinez C, Katholing A, Wallenhorst C, Freedman SB (2016) Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study. Thromb Haemost 115(1):31–39. https://doi.org/10.1160/TH15-04-0350

    Article  PubMed  Google Scholar 

  44. Janzic A, Kos M (2015) Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of Warfarin anticoagulation control. Pharmacoeconomics 33(4):395–408. https://doi.org/10.1007/s40273-014-0246-7

    Article  PubMed  Google Scholar 

  45. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener H‑C, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GYH, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37(38):2893–2962. https://doi.org/10.1093/eurheartj/ehw210

    Article  PubMed  Google Scholar 

  46. Athanasakis K, Boubouchairopoulou N, Karampli E, Tarantilis F, Savvari P, Bilitou A, Kyriopoulos J (2017) Cost effectiveness of Apixaban versus Warfarin or Aspirin for stroke prevention in patients with atrial fibrillation: a Greek perspective. Am J Cardiovasc Drugs 17(2):123–133. https://doi.org/10.1007/s40256-016-0204-1

    Article  CAS  PubMed  Google Scholar 

  47. Lanitis T, Cotte FE, Gaudin AF, Kachaner I, Kongnakorn T, Durand-Zaleski I (2014) Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin. J Med Econ 17(8):587–598. https://doi.org/10.3111/13696998.2014.923891

    Article  CAS  PubMed  Google Scholar 

  48. Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED, Fox KA (2016) Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 375(25):2423–2434. https://doi.org/10.1056/NEJMoa1611594

    Article  CAS  PubMed  Google Scholar 

  49. 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, Committee R‑DPS, Investigators (2017) Dual antithrombotic therapy with Dabigatran after PCI in atrial fibrillation. N Engl J Med 377(16):1513–1524. https://doi.org/10.1056/NEJMoa1708454

    Article  CAS  PubMed  Google Scholar 

  50. Cohen DJ, Reynolds MR (2008) Interpreting the results of cost-effectiveness studies. J Am Coll Cardiol 52(25):2119–2126. https://doi.org/10.1016/j.jacc.2008.09.018

    Article  PubMed  PubMed Central  Google Scholar 

  51. Vaartjes I, van Dis I, Grobbee DE, Bots ML (2010) The dynamics of mortality in follow-up time after an acute myocardial infarction, lower extremity arterial disease and ischemic stroke. BMC Cardiovasc Disord 10:57. https://doi.org/10.1186/1471-2261-10-57

    Article  PubMed  PubMed Central  Google Scholar 

  52. Suleiman M, Khatib R, Agmon Y, Mahamid R, Boulos M, Kapeliovich M, Levy Y, Beyar R, Markiewicz W, Hammerman H, Aronson D (2006) Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C‑reactive protein. J Am Coll Cardiol 47(5):962–968. https://doi.org/10.1016/j.jacc.2005.10.055

    Article  PubMed  Google Scholar 

  53. Park TH, Saposnik G, Bae HJ, Lee SJ, Lee KB, Lee J, Park JM, Choi JC, Kim DE, Cho YJ, Kim JT, Cha JK, Lee J, Yu KH, Lee BC, Yoon BW (2013) The iScore predicts functional outcome in Korean patients with ischemic stroke. Stroke 44(5):1440–1442. https://doi.org/10.1161/STROKEAHA.111.000748

    Article  PubMed  Google Scholar 

  54. Shah R, Hellkamp A, Lokhnygina Y, Becker R, Berkowitz SD, Breithardt G, Hacke W, Halperin JL, Hankey GJ, Fox KAA, Nessel CC, Mahaffey KW, Piccini JP, Singer DE, Patel MR, Investigators obotRASC (2016) Use of concomitan aspirin in patients with atrial fibrillation: findings from the ROCKET AF trial. Am Heart J 179:77–86

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Electrophysiology, Heart Centre Leipzig, University of Leipzig, Struempellstraße 39, 04289, Leipzig, Germany

    K. Bode MD, MSc & G. Hindricks

  2. Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands

    J. M. ten Berg

  3. Cardiovascular Research Institute & Department of Emergency Medicine, Wayne State University, Detroit, MI, USA

    P. Whittaker

  4. Department of Health Policy, London School of Economics and Political Science, London, UK

    K. Bode MD, MSc, J. M. ten Berg & P. Whittaker

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K. Bode and P. Whittaker declare that they have no competing interests. J.M. ten Berg has received speaker’s fees from Astra Zeneca, BMS, Pfizer, the Medicines Company, Boehringer Ingelheim, and Lilly and has received a grant from Astra Zeneca and ZonMw. G. Hindricks reported grants for the Heart Center Leipzig from Abbott and Boston Scientific but has not received personal payments for his services.

This article does not contain any studies with human participants or animals performed by any of the authors.

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J.M. ten Berg and P. Whittaker shared senior authorship.

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Bode, K., Hindricks, G., ten Berg, J.M. et al. Anticoagulant plus antiplatelet therapy for atrial fibrillation. Herz 45, 564–571 (2020). https://doi.org/10.1007/s00059-018-4747-6

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