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Thromb Haemost 2018; 118(05): 906-913
DOI: 10.1055/s-0038-1637755
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH Stuttgart

International Normalized Ratio Targets for Left-Sided Mechanical Valve Replacement

Saurabh Gupta
1   Department of Surgery, McMaster University, Hamilton, Ontario, Canada
2   Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
,
Emilie P. Belley-Cote
2   Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
3   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
4   Perioperative and Surgery Program, Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Anisha Sarkaria
5   Department of Medicine, School of Medicine, Queen's University, Kingston, Ontario, Canada
,
Arjun Pandey
6   Experimental Thrombosis and Atherosclerosis Program, Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
7   Department of Health Sciences, McMaster University, Hamilton, Ontario, Canada
,
Jessica Spence
2   Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
8   Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
,
Graham McClure
2   Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
9   Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Puru Panchal
7   Department of Health Sciences, McMaster University, Hamilton, Ontario, Canada
,
Iqbal H. Jaffer
1   Department of Surgery, McMaster University, Hamilton, Ontario, Canada
6   Experimental Thrombosis and Atherosclerosis Program, Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Kevin An
9   Michael DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
,
John Eikelboom
3   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
4   Perioperative and Surgery Program, Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Richard P. Whitlock
1   Department of Surgery, McMaster University, Hamilton, Ontario, Canada
2   Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
4   Perioperative and Surgery Program, Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
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Publikationsverlauf

12. Oktober 2017

01. Februar 2018

Publikationsdatum:
03. April 2018 (online)

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Abstract

Background Guidelines recommend higher international normalized ratio (INR) targets for patients with mechanical valves believed to be at higher risk for thromboembolism. Higher INR targets are associated with increased bleeding risk. We performed a systematic review and meta-analysis assessing effects of lower and higher INR targets on thromboembolic and bleeding risk in patients with mechanical heart valves.

Methods We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized controlled trials (RCTs) evaluating lower versus higher INR targets for adults with bileaflet mechanical valves. We performed title and abstract screening, full-text review, risk of bias evaluation and data collection independently and in duplicate. We pooled data using a random effects model and used the Grading of Recommendations Assessment, Development and Evaluation framework to evaluate overall quality of evidence.

Results We identified six RCTs (n = 5,497). Lower INR targets were associated with significantly less bleeding—22% versus 40% (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.31, 0.93, p = 0.03, very low quality). There was no difference in thromboembolism—2% in both groups (RR: 1.28, 95% CI: 0.88, 1.85, p = 0.20, very low quality) or mortality—5.5% with lower INR targets versus 8.5% (RR: 1.00, 95% CI: 0.82, 1.21, p = 0.47, moderate quality).

Conclusion In patients with mechanical valves, higher INR targets are not supported by current evidence, which is of very low quality. In fact, our systematic review suggests that lower INR targets offer significantly lower bleeding risks with no significant difference in thromboembolic risk.

Keywords

controlled trials - oral anticoagulants - thrombosis - cardiology - warfarin

Supplementary Material

 

  • References

  • 1 Dasi LP, Simon HA, Sucosky P, Yoganathan AP. Fluid mechanics of artificial heart valves. Clin Exp Pharmacol Physiol 2009; 36 (02) 225-237
    CrossrefPubMedGoogle Scholar
  • 2 Jaffer IH, Whitlock RP. A mechanical heart valve is the best choice. Heart Asia 2016; 8 (01) 62-64
    PubMedGoogle Scholar
  • 3 Pibarot P, Dumesnil JG. Prosthetic heart valves: selection of the optimal prosthesis and long-term management. Circulation 2009; 119 (07) 1034-1048
    CrossrefPubMedGoogle Scholar
  • 4 Bloomfield P. Choice of heart valve prosthesis. Heart 2002; 87 (06) 583-589
    CrossrefPubMedGoogle Scholar
  • 5 Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl): e576S-e600S
    CrossrefPubMedGoogle Scholar
  • 6 Vahanian A, Alfieri O, Andreotti F. , et al; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012; 33 (19) 2451-2496
    CrossrefPubMedGoogle Scholar
  • 7 Nishimura RA, Otto CM, Bonow RO. , et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2017; 135 (25) e1159-e1195
    CrossrefPubMedGoogle Scholar
  • 8 Schein JR, White CM, Nelson WW, Kluger J, Mearns ES, Coleman CI. Vitamin K antagonist use: evidence of the difficulty of achieving and maintaining target INR range and subsequent consequences. Thromb J 2016; 14: 14
    CrossrefPubMedGoogle Scholar
  • 9 Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJ, Vandenbroucke JP, Briët E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995; 333 (01) 11-17
    CrossrefPubMedGoogle Scholar
  • 10 Kaneko T, Aranki SF. Anticoagulation for prosthetic valves. Thrombosis 2013; 2013: 346752
    PubMedGoogle Scholar
  • 11 January CT, Wann LS, Alpert JS. , et al; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130 (23) 2071-2104
    CrossrefPubMedGoogle Scholar
  • 12 Kirchhof P, Benussi S, Kotecha D. , et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg 2016; 50 (05) e1-e88
    CrossrefPubMedGoogle Scholar
  • 13 Singer DE, Albers GW, Dalen JE. , et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 Suppl): 546S-592S
    CrossrefPubMedGoogle Scholar
  • 14 Olesen JB, Lip GY, Hansen ML. , et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011; 342: d124
    CrossrefPubMedGoogle Scholar
  • 15 Olesen JB, Torp-Pedersen C, Hansen ML, Lip GY. The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort study. Thromb Haemost 2012; 107 (06) 1172-1179
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Horstkotte D, Bergemann R, Althaus U. , et al. German experience with low intensity anticoagulation (GELIA): protocol of a multi-center randomized, prospective study with the St. Jude Medical valve. J Heart Valve Dis 1993; 2 (04) 411-419
    PubMedGoogle Scholar
  • 17 Hering D, Piper C, Bergemann R. , et al. Thromboembolic and bleeding complications following St. Jude Medical valve replacement: results of the German Experience With Low-Intensity Anticoagulation Study. Chest 2005; 127 (01) 53-59
    CrossrefPubMedGoogle Scholar
  • 18 Puskas J, Gerdisch M, Nichols D. , et al; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg 2014; 147 (04) 1202-1210 , discussion 1210–1211
    CrossrefPubMedGoogle Scholar
  • 19 Lip GYH, Collet JP, de Caterina R. , et al. Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: executive summary of a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, Endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE). Thromb Haemost 2017; 117 (12) 2215-2236
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 20 Covidence systematic review software VHI, Melbourne, Australia. Available at: www.covidence.org . Accessed August 2, 2016
    PubMed
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Tool to Assess Risk of Bias in Cohort Studies by the CLARITY Group at McMaster University. Available at: https://www.evidencepartners.com/resources/methodological-resources/ . Accessed August 4, 2017
    PubMed
  • 23 Manager R. . (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre TCC; 2014
    PubMed
  • 24 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7 (03) 177-188
    CrossrefPubMedGoogle Scholar
  • 25 Guyatt GH, Oxman AD, Vist GE. , et al; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336 (7650): 924-926
    CrossrefPubMedGoogle Scholar
  • 26 Acar J, Iung B, Boissel JP. , et al. AREVA: multicenter randomized comparison of low-dose versus standard-dose anticoagulation in patients with mechanical prosthetic heart valves. Circulation 1996; 94 (09) 2107-2112
    CrossrefPubMedGoogle Scholar
  • 27 Koertke H, Zittermann A, Wagner O. , et al; Christ of Huth. Telemedicine-guided, very low-dose international normalized ratio self-control in patients with mechanical heart valve implants. Eur Heart J 2015; 36 (21) 1297-1305
    CrossrefPubMedGoogle Scholar
  • 28 Pengo V, Palareti G, Cucchini U. , et al; participating centers of Italian Federation of Anticoagulation Clinics (FCSA). Low-intensity oral anticoagulant plus low-dose aspirin during the first six months versus standard-intensity oral anticoagulant therapy after mechanical heart valve replacement: a pilot study of low-intensity warfarin and aspirin in cardiac prostheses (LIWACAP). Clin Appl Thromb Hemost 2007; 13 (03) 241-248
    CrossrefPubMedGoogle Scholar
  • 29 Torella M, Torella D, Chiodini P. , et al. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the “LOWERING-IT” trial. Am Heart J 2010; 160 (01) 171-178
    CrossrefPubMedGoogle Scholar
  • 30 Levine GN, Bates ER, Bittl JA. , et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2016; 68 (10) 1082-1115
    CrossrefPubMedGoogle Scholar
  • 31 Kido K, Ball J. Optimal intensity of warfarin therapy in patients with mechanical aortic valves. J Pharm Pract 2017; DOI: 10.1177/0897190017734765.
    CrossrefPubMedGoogle Scholar
  • 32 Takkenberg JJ, Puvimanasinghe JP, van Herwerden LA. Optimal target international normalized ratio for patients with mechanical heart valves. J Am Coll Cardiol 2004; 44 (05) 1142-1143
    CrossrefPubMedGoogle Scholar
  • 33 Vink R, Kraaijenhagen RA, Hutten BA. , et al. The optimal intensity of vitamin K antagonists in patients with mechanical heart valves: a meta-analysis. J Am Coll Cardiol 2003; 42 (12) 2042-2048
    CrossrefPubMedGoogle Scholar
  • 34 Connolly SJ. Anticoagulant-related bleeding and mortality. J Am Coll Cardiol 2016; 68 (23) 2522-2524
    CrossrefPubMedGoogle Scholar
  • 35 Steinberg BA, Simon DN, Thomas L. , et al; Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators and Patients. Management of major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants compared with warfarin in clinical practice (from phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]). Am J Cardiol 2017; 119 (10) 1590-1595
    CrossrefPubMedGoogle Scholar
  • 36 Merinopoulos I, Venables P, Chalmers I, Vassiliou V. NOAC or warfarin for atrial fibrillation: does time in therapeutic range matter?. Recent Adv Cardiovasc Drug Discov 2015; 10 (01) 60-64
    PubMedGoogle Scholar
  • 37 Grzymala-Lubanski B, Labaf A, Englund E, Svensson PJ, Själander A. Mechanical heart valve prosthesis and warfarin - treatment quality and prognosis. Thromb Res 2014; 133 (05) 795-798
    CrossrefPubMedGoogle Scholar
  • 38 Leiria TL, Lopes RD, Williams JB, Katz JN, Kalil RA, Alexander JH. Antithrombotic therapies in patients with prosthetic heart valves: guidelines translated for the clinician. J Thromb Thrombolysis 2011; 31 (04) 514-522
    CrossrefPubMedGoogle Scholar