Skip to main content
SpringerLink
Log in

New oral anticoagulants for nonvalvular atrial fibrillation with peripheral artery disease: a meta-analysis

Neue orale Antikoagulanzien bei nichtvalvulärem Vorhofflimmern und gleichzeitiger peripherer arterieller Verschlusskrankheit: eine Metaanalyse

  • Review Article
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Background

New oral anticoagulants (NOACs) are as effective and safe as warfarin for patients with non-valvular atrial fibrillation (NVAF). Limited evidence is available regarding outcomes for NVAF patients with peripheral artery disease (PAD).

Methods

A systematic search of Medline, Embase, and the Cochrane Library was performed. Two reviewers independently performed data extraction and quality assessment using the Cochrane Collaboration tool for assessing risk of bias. All primary publications and secondary analyses comparing NOACs with other oral anticoagulation regimens for the prevention of stroke in patients with both NVAF and PAD from phase III clinical trials were evaluated. The primary outcomes were stroke, systemic embolism (SE), major bleeding, and intracranial hemorrhage (ICH), and the secondary outcomes were cardiovascular (CV) mortality, all-cause mortality, and myocardial infarction (MI).

Results

Three articles were included in this study. The pooled results showed a relative risk for stroke/SE with NOACs of 0.86 (95% confidence interval [CI]: 0.53–1.39), for major bleeding, 1.12 (95% CI: 0.70–1.81), for ICH, 0.47 (95% CI: 0.16–1.36), for CV mortality, 0.77 (95% CI: 0.57–1.04), for all-cause mortality, 0.91 (95% CI: 0.70–1.19), and for MI, 1.10 (95% CI: 0.64–1.90).

Conclusion

The findings show that NOACs are effective and safe for preventing stroke/SE in patients with both NVAF and PAD.

Zusammenfassung

Hintergrund

Neue orale Antikoagulanzien (NOAK) sind ebenso wirksam und sicher wie Warfarin für Patienten mit nichtvalvulärem Vorhofflimmern (NVAF). Hinsichtlich der Ergebnisse für NVAF-Patienten mit peripherer arterieller Verschlusskrankheit (pAVK) besteht jedoch nur begrenzt Evidenz.

Methoden

In den Datenbanken Medline, Embase und der Cochrane Library wurde eine systematische Suche durchgeführt. Unabhängig extrahierten 2 Untersucher die Daten und beurteilten die Qualität anhand des Instruments der Cochrane Collaboration zur Beurteilung des Risikos für Bias. Ausgewertet wurden alle Primärpublikationen und Sekundäranalysen, in denen NOAK mit anderen Schemata unter Einsatz oraler Antikoagulanzien zur Schlaganfallprävention bei Patienten, die sowohl NVAF als auch pAVK aufwiesen, in klinischen Phase-III-Studien verglichen wurden. Die primären Endpunkte waren Schlaganfall, systemische Embolien (SE), schwere Blutungen und intrakranielle Hämorrhagien (ICH); die sekundären Endpunkte waren kardiovaskulär bedingte (CV-)Mortalität, Mortalität aus sämtlichen Ursachen und Myokardinfarkt (MI)

Ergebnisse

In die vorliegende Studie wurden 3 Artikel einbezogen. Die gepoolten Ergebnisse zeigten ein relatives Risiko für Schlaganfall/SE unter NOAK von 0,86 (95%-Konfidenzintervall, 95%-KI: 0,53–1,39), für schwere Blutungen lag es bei 1,12 (95%-KI: 0,70–1,81), für ICH bei 0,47 (95%-KI: 0,16–1,36), für CV-Mortalität bei 0,77 (95%-KI: 0,57–1,04), für Mortalität aus sämtlichen Ursachen bei 0,91 (95%-KI: 0,70–1,19) und für MI bei 1,10 (95%-KI: 0,64–1,90).

Schlussfolgerung

Die vorliegenden Ergebnisse zeigen, dass NOAK zur Prävention von Schlaganfall/SE bei Patienten mit NVAF und gleichzeitiger pAVK wirksam und sicher sind.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Chugh SS, Havmoeller R, Narayanan K et al (2014) Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129:837–847

    Article  Google Scholar 

  2. Fowkes FG, Rudan D, Rudan I et al (2013) Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 382:1329–1340

    Article  Google Scholar 

  3. Lip GY, Nieuwlaat R, Pisters R et al (2010) Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest 137:263–272

    Article  Google Scholar 

  4. Aguilar E, Garcia-Diaz AM, Sanchez Munoz-Torrero JF et al (2012) Clinical outcome of stable outpatients with coronary, cerebrovascular or peripheral artery disease, and atrial fibrillation. Thromb Res 130:390–395

    Article  CAS  Google Scholar 

  5. Goto S, Bhatt DL, Rother J et al (2008) Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. Am Heart J 156:855–863

    Article  Google Scholar 

  6. Winkel TA, Hoeks SE, Schouten O et al (2010) Prognosis of atrial fibrillation inpatients with symptomatic peripheral arterial disease: data from the REduction of Atherothrombosis for Continued Health (REACH) Registry. Eur J Vasc Endovasc Surg 40:9–16

    Article  CAS  Google Scholar 

  7. Olesen JB, Lip GY, Lane DA et al (2012) Vascular disease and stroke risk in atrial fibrillation: a nationwide cohort study. Am J Med 125:826 e13–826 e23

    Article  Google Scholar 

  8. Steffel J, Verhamme P, Potpara TS et al (2018) The 2018 European Heart Rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 39(16):1330–1393. https://doi.org/10.1093/eurheartj/ehy136

    Article  CAS  PubMed  Google Scholar 

  9. Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151

    Article  CAS  Google Scholar 

  10. Patel MR, Mahaffey KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365(10):883–891

    Article  CAS  Google Scholar 

  11. Granger CB, Alexander JH, McMurray JJ et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365(11):981–992

    Article  CAS  Google Scholar 

  12. Giugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369(22):2093–2104

    Article  CAS  Google Scholar 

  13. Deitelzweig S, Farmer C, Luo X et al (2017) Risk of major bleeding in patients with non-valvular atrial fibrillation treated with oral anticoagulants: a systematic review of real-world observational studies. Curr Med Res Opin 33(9):1583–1594

    Article  CAS  Google Scholar 

  14. Li XS, Deitelzweig S, Keshishian A et al (2017) Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice. a propensity-matched analysis of 76,940 patients. Thromb Haemost 117(6):1072–1082

    Article  Google Scholar 

  15. Hart RG, Diener HC, Yang S et al (2012) Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke 43:1511–1517

    Article  CAS  Google Scholar 

  16. Gage BF, van Walraven C, Pearce L et al (2004) Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 110:2287–2292

    Article  CAS  Google Scholar 

  17. Lopes RD, Steffel J, Di Fusco M et al (2018) Effectiveness and safety of anticoagulants in adults with non-valvular atrial fibrillation and concomitant coronary/peripheral artery disease. Am J Med 131:1075–1085.e4. https://doi.org/10.1016/j.amjmed.2018.05.007

    Article  CAS  PubMed  Google Scholar 

  18. Coleman CI, Baker WL, Meinecke AK et al (2019) Effectiveness and safety of rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and coronary or peripheral artery disease. Eur Heart J 40(1 Supplement):4778. https://doi.org/10.1093/eurheartj/ehz745.1154

    Article  Google Scholar 

  19. Hu PT, Lopes RD, Stevens SR et al (2017) Efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation and peripheral artery disease: insights from the ARISTOTLE trial. J Am Heart Assoc 6(1):e4699. https://doi.org/10.1161/JAHA.116.004699

    Article  PubMed  PubMed Central  Google Scholar 

  20. Jones WS, Hellkamp AS, Halperin J et al (2014) Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF. Eur Heart J 35(4):242–249. https://doi.org/10.1093/eurheartj/eht492

    Article  CAS  PubMed  Google Scholar 

  21. Cunningham JW, Giugliano RP, Braunwald E et al (2016) Edoxaban versus warfarin in 841 patients with atrial fibrillation and peripheral arterial disease: insights from the engage AF-TIMI 48 trial. J Am Coll Cardiol 67(13 Supplement):2262. https://doi.org/10.1016/S0735-1097(16)32263-X

    Article  Google Scholar 

  22. European Stroke Organisation, Tendera M, Aboyans V et al (2011) ESC guidelines on the diagnosis and treatment of peripheral artery diseases: document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J 32:2851–2906

    Article  Google Scholar 

  23. Vrsalović M, Vučur K, Car B et al (2015) C‑reactive protein, renal function, and cardiovascular outcome in patients with symptomatic peripheral artery disease and preserved left ventricular systolic function. Croat Med J 56:351–356

    Article  Google Scholar 

  24. Vrsalovic M, Vucur K, Vrsalovic Presecki A et al (2017) Impact of diabetes on mortality in peripheral artery disease: a meta-analysis. Clin Cardiol 40(5):287–291. https://doi.org/10.1002/clc.22657

    Article  PubMed  Google Scholar 

  25. Alberts MJ, Bhatt DL, Mas JL et al (2009) Three-year follow-up and event rates in the international REduction of Atherothrombosis for Continued Health Registry. Eur Heart J 30(19):2318–2326. https://doi.org/10.1093/eurheartj/ehp355

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lip GY, Windecker S, Huber K et al (2014) Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Eur Heart J 35:3155–3179

    Article  CAS  Google Scholar 

  27. Hirsh J, Dalen J, Anderson DR et al (2001) Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 119:8S–21S

    Article  CAS  Google Scholar 

  28. Ansell J, Hirsh J, Hylek E et al (2008) Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 133:160S–198S

    Article  CAS  Google Scholar 

  29. Go AS, Hylek EM, Borowsky LH et al (1999) Warfarin use among ambulatory patients with nonval vular atrial fibrillation: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. Ann Intern Med 131:927–934

    Article  CAS  Google Scholar 

  30. Eriksson BI, Quinlan DJ, Weitz JI (2009) Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development. Clin Pharmacokinet 48:1–22

    Article  CAS  Google Scholar 

  31. De Caterina R, Husted S, Wallentin L et al (2013) Position paper of the ESC working group on thrombosis-task force on anticoagulants in heart disease. Thromb Haemost 109:569–579

    Article  Google Scholar 

  32. Vrsalović M, Presečki AV (2017) Atrial fibrillation and risk of cardiovascular events and mortality in patients with symptomatic peripheral artery disease: a meta-analysis of prospective studies. Clin Cardiol 40(12):1231–1235. https://doi.org/10.1002/clc.22813

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hohnloser SH, Oldgren J, Yang S et al (2012) Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation 125:669–676. https://doi.org/10.1161/CIRCULATIONAHA.111.055970

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I would like to thank Editage (www.editage.cn) for English language editing.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Thyroid Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, 610041, Chengdu, Sichuan, China

    Qiuyu Meng M.D.

  2. Department of Cardiology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, 610041, Chengdu, Sichuan, China

    Zhifu Cen Ph.D.

Authors
  1. Qiuyu Meng M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhifu Cen Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made the same contribution, including research execution and article revision.

Corresponding author

Correspondence to Zhifu Cen Ph.D..

Ethics declarations

Conflict of interest

Q. Meng and Z. Cen declare that they have no competing interests.

The ethical guidelines of the studies analyzed in this article are provided within the respective study. This article does not contain any studies with human participants or animals performed by any of the authors.

Caption Electronic Supplementary Material

Supplementary Table 1. Outcomes of each study

Supplementary Table 2. Search strategy

59_2020_4970_MOESM3_ESM.tif

Supplementary Fig. 1. Funnel plot. a Stroke/systemic embolization (SE); b major bleeding; c intracranial hemorrhage (ICH); d cardiovascular death (CV); e all-cause death; f myocardial infarction (MI). All funnel plots were symmetrical. The Egger test proved that there was no publication bias in all the results (Pa = 0.272, Pb = 0.568, Pc = 0.436, Pd = 0.204).

59_2020_4970_MOESM4_ESM.docx

Supplementary Fig. 2. Risk of bias summary and graph. a Risk of bias summary. Review of authors’ judgments regarding each risk-of-bias item for each study included. b Risk of bias graph. Review of authors’ judgments regarding each risk-of-bias item presented as percentages across all studies included.

59_2020_4970_MOESM5_ESM.docx

Supplementary Fig. 3. a Forest plot of outcomes after removing Hu 2017. b Forest plot of outcomes after removing Jones 2014. c Forest plot of outcomes after removing Cunningham 2016. SE, systemic embolization; CV death, cardiovascular death; ICH, intracranial hemorrhage

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meng, Q., Cen, Z. New oral anticoagulants for nonvalvular atrial fibrillation with peripheral artery disease: a meta-analysis. Herz 46, 352–358 (2021). https://doi.org/10.1007/s00059-020-04970-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-020-04970-8

Keywords

Schlüsselwörter

Search

Navigation