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Thromb Haemost 2009; 101(03): 527-534
DOI: 10.1160/TH08-08-0499
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

How effective are dose-adjusted warfarin and aspirin for the prevention of stroke in patients with chronic atrial fibrillation?

An analysis of the UK General Practice Research Database
Stephan Rietbrock
1   General Practice Research Database, Medicines and Healthcare products Regulatory Agency, London, UK
,
Jonathan M. Plumb
2   Boehringer Ingelheim, Ingelheim am Rhein, Germany
,
Arlene M. Gallagher
1   General Practice Research Database, Medicines and Healthcare products Regulatory Agency, London, UK
,
Tjeerd P. van Staa
1   General Practice Research Database, Medicines and Healthcare products Regulatory Agency, London, UK
3   Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
› Author AffiliationsFinancial support: The study was funded by Boehringer Ingelheim International GmbH (BI). BI has a compound in clinical development for stroke prevention in patients with atrial fibrillation.
Further Information

Publication History

Received: 05 August 2008

Accepted after major revision: 03 February 2008

Publication Date:
24 November 2017 (online)

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Summary

The objective of this study was to evaluate the rate of stroke associated with aspirin and warfarin in routine clinical practice. The study included patients aged 40+ with chronic atrial fibrillation (cAF) registered in the UK General Practice Research Database. The outcome was the rate of stroke during current, past and no use of aspirin and warfarin. The study included 51,807 cAF patients. There was no difference in the rate of stroke between current and past use of aspirin (relative rate [RR]=1.04 [95% confidence interval (CI) 0.94 – 1.15]), while the rate of stroke was reduced during current warfarin use compared to past use (RR=0.62 [95% CI 0.54 – 0.71]). For warfarin, a pattern of lower rates of stroke during current exposure and higher rates with past exposure was seen only in patients treated for at least 6–12 months. For aspirin, no changes in the rates of stroke were observed with discontinuation of aspirin. The effectiveness of warfarin was dependent on the level of anticoagulation, with optimal risk reduction occurring within the recommended international normalised ratio (INR) range of 2.0 to 3.0. The proportion of patients achieving a stable INR within the target therapeutic range was at its lowest during the first three months of warfarin treatment. In conclusion, the results of this study support the effectiveness of warfarin treatment to reduce the rate of stroke in cAF patients in the general clinical practice setting, however the risk reduction is lower than that reported in clinical trials.

Keywords

Stroke prevention - epidemiological studies - risk factors
 

  • References

  • 1 Fuster V, Ryden LE, Cannom DS. et al. ACC/AHA/ ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114: e257-354.
    CrossrefPubMedSearch in Google Scholar
  • 2 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.
    CrossrefPubMedSearch in Google Scholar
  • 3 Majeed A, Moser K, Carroll K. Trends in the prevalence and management of atrial fibrillation in general practice in England and Wales, 1994–1998: Analysis of data from the general practice research database. Heart 2001; 86: 284-288.
    CrossrefPubMedSearch in Google Scholar
  • 4 DeWilde S, Carey IM, Emmas C. et al. Trends in the prevalence of diagnosed atrial fibrillation, its treatment with anticoagulation and predictors of such treatment in UK primary care. Heart 2006; 92: 1064-1070.
    CrossrefPubMedSearch in Google Scholar
  • 5 Walley T, Mantgani A. The UK General Practice Research Database. Lancet 1997; 350: 1097-1099.
    CrossrefPubMedSearch in Google Scholar
  • 6 Rietbrock S, Heeley E, Plumb J. et al. Chronic atrial fibrillation: incidence, prevalence and prediction of stroke using the CHADS2 risk stratification scheme. Am Heart J 2008; 156: 57-64.
    CrossrefPubMedSearch in Google Scholar
  • 7 Gage BF, Waterman AD, Shannon W. et al. Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
    CrossrefPubMedSearch in Google Scholar
  • 8 Gallagher A, Rietbrock S, Plumb J. et al. Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis?. J Thromb Haemost 2008; 6: 1500-1506.
    CrossrefPubMedSearch in Google Scholar
  • 9 Go AS, Hylek EM, Chang Y. et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?. J Am Med Assoc 2003; 290: 2685-2692.
    CrossrefPubMedSearch in Google Scholar
  • 10 Frost L, Johnsen SP, Pedersen L. et al. Atrial fibrillation or flutter and stroke: a Danish population-based study of the effectiveness of oral anticoagulation in clinical practice. J Intern Med 2002; 252: 64-69.
    CrossrefPubMedSearch in Google Scholar
  • 11 Hylek EM, Go AS, Chang Y. et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349: 1019-1026.
    CrossrefPubMedSearch in Google Scholar
  • 12 ACTIVE Writing Group of the ACTIVE Investigators. Connolly S, Pogue J, Hart R. et al. 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 2006; 367: 1903-1912.
    CrossrefPubMedSearch in Google Scholar
  • 13 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.
    CrossrefPubMedSearch in Google Scholar
  • 14 Diener HC, Cunha L, Forbes C. et al. European stroke prevention study 2: dipyridamole and acetylsalicylic acid in the prevention of stroke. J Neurol Sci 1996; 143: 1-13.
    CrossrefPubMedSearch in Google Scholar
  • 15 Peterson P, Boysen G, Godtfredsen J. et al. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. Lancet 1989; 1: 175-179.
    PubMedSearch in Google Scholar
  • 16 Stroke prevention in atrial fibrillation investigators.. Stroke prevention in atrial fibrillation study: final results. Circulation 1991; 84: 527-539.
    CrossrefPubMedSearch in Google Scholar
  • 17 Dalen JE. Aspirin to prevent heart attack and stroke: what’s the right dose. Am J Med 2006; 119: 198-202.
    CrossrefPubMedSearch in Google Scholar
  • 18 Mant J, Hobbs FD, Fletcher K. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493-503.
    CrossrefPubMedSearch in Google Scholar
  • 19 Johnston SC. Transient ischemic attack: a dangerous harbinger and an opportunity to intervene. Semin Neurol 2005; 25: 362-370.
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Mant JW. Pro: ‘warfarin should be the drug of choice for thromboprophylaxis in elderly patients with atrial fibrillation’. Why warfarin should really be the drug of choice for stroke prevention in elderly patients with atrial fibrillation. Thromb Haemost 2008; 100: 14-15.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Hylek EM. Contra: ‘warfarin should be the drug of choice for thromboprophylaxis in elderly patients with atrial fibrillation’. Caveats regarding use of anticoagulant therapy among elderly patients with atrial fibrillation. Thromb Haemost 2008; 100: 16-17.
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Ruigómez A, Johansson S, Wallander M-A. et al. Incidence of chronic atrial fibrillation in general practice and its treatment pattern. J Clin Epidemiol 2002; 55: 358-363.
    CrossrefPubMedSearch in Google Scholar
  • 23 Lip GYH. Paroxysmal atrial fibrillation, stroke risk and thromboprophylaxis. Thromb Haemost 2008; 100: 11-13.
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 McBane RD, Hodge DO, Wysokinski WE. Clinical and echocardiographic measures governing thromboembolism destination in atrial fibrillation. Thromb Haemost 2008; 99: 951-955.
    Thieme ConnectPubMedSearch in Google Scholar