Statin use and risk of recurrent venous thrombosis: results from the MEGA follow-up study.

Sigrid K Brækkan, Camila Caram-Deelder, Bob Siegerink, Astrid van Hylckama Vlieg, Saskia le Cessie, Frits R Rosendaal, Suzanne C Cannegieter, Willem M Lijfering
Author Information
  1. Sigrid K Brækkan: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  2. Camila Caram-Deelder: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  3. Bob Siegerink: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  4. Astrid van Hylckama Vlieg: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  5. Saskia le Cessie: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  6. Frits R Rosendaal: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  7. Suzanne C Cannegieter: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.
  8. Willem M Lijfering: Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands.

Abstract

INTRODUCTION: Whether statin use after first venous thrombosis reduces the risk of recurrence is uncertain. Therefore, we aimed to examine the risk of recurrent venous thrombosis in statin users vs non-users.
METHODS: Patients with a first venous thrombosis were recruited from the MEGA follow-up study. Information on statin use was obtained by linkage to the Dutch Foundation for Pharmaceutical Statistics register. Linkage was successful in 54% of all patients (n = 2,547). Cox-regression models with statin-exposure as a time-dependent co-variate were used to estimate hazard ratios (HR) with 95% confidence intervals (CI 95) for recurrence.
RESULTS: Statin therapy was continued in 153 (6.0%) patients and initiated in 233 (9.1%) patients during a median follow-up of 5.7 years. There were 367 recurrent venous thrombotic events, of which 32 occurred among statin users. Incident statin use was associated with 22% reduced risk of recurrence after multivariable adjustments (HR 0.78, CI 95: 0.46-1.31), and 13% reduced risk after propensity score adjustment (HR 0.87, CI 95: 0.52-1.47). Statin use seemed not to have an effect on recurrence in patients with an unprovoked first event (multivariable HR 1.03, CI 95: 0.54-1.98), but the statistical power was low due to few events and the results must be interpreted with caution. In general, the risk estimates were slightly attenuated when prevalent users were included in the analyses.
CONCLUSION: Our findings suggest that statins may have a modest decreasing effect on the risk of recurrent venous thrombosis. While we took care to minimize bias and confounding, the causality of the association is still unsettled.

Keywords

References

  1. Am J Epidemiol. 2012 Feb 15;175(4):250-62 [PMID: 22223710]
  2. Lancet. 1999 Apr 3;353(9159):1167-73 [PMID: 10209995]
  3. Eur J Epidemiol. 2010 Apr;25(4):245-51 [PMID: 20358262]
  4. Thromb Res. 2012 Dec;130(6):859-63 [PMID: 22939687]
  5. Res Pract Thromb Haemost. 2017 May 25;1(1):112-119 [PMID: 30046679]
  6. Lancet. 2007 Nov 24;370(9601):1773-9 [PMID: 18037081]
  7. Eur Heart J. 2010 May;31(10):1248-56 [PMID: 20031958]
  8. JAMA. 2008 Mar 19;299(11):1306-14 [PMID: 18349091]
  9. JAMA. 2005 Feb 9;293(6):715-22 [PMID: 15701913]
  10. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934 [PMID: 24239923]
  11. J Thromb Haemost. 2007 Apr;5(4):692-9 [PMID: 17367492]
  12. J Thromb Haemost. 2015 Oct;13(10):1823-32 [PMID: 26270389]
  13. J Thromb Haemost. 2014 Aug;12(8):1207-15 [PMID: 24818818]
  14. QJM. 2011 Feb;104(2):109-24 [PMID: 20934984]
  15. Circulation. 2011 Sep 27;124(13):1435-41 [PMID: 21900083]
  16. Thromb Haemost. 2016 Jun 2;115(6):1220-8 [PMID: 26819144]
  17. Circulation. 2004 Jul 13;110(2):227-39 [PMID: 15249516]
  18. Am J Epidemiol. 2006 Jun 15;163(12):1149-56 [PMID: 16624967]
  19. Eur Heart J. 2013 Jun;34(24):1800-6 [PMID: 23396492]
  20. J Thromb Haemost. 2007 Nov;5(11):2186-92 [PMID: 17697136]
  21. Epidemiology. 2004 Sep;15(5):615-25 [PMID: 15308962]
  22. J Thromb Haemost. 2016 Jul;14(7):1384-92 [PMID: 27061794]
  23. JAMA. 2005 May 18;293(19):2352-61 [PMID: 15900005]
  24. Lancet. 2010 Feb 27;375(9716):735-42 [PMID: 20167359]
  25. N Engl J Med. 2009 Apr 30;360(18):1851-61 [PMID: 19329822]
  26. Am J Epidemiol. 2015 Nov 15;182(10):826-33 [PMID: 26507305]
  27. PLoS Med. 2012;9(9):e1001310 [PMID: 23028261]
  28. Lancet. 2007 Nov 24;370(9601):1781-90 [PMID: 17559928]
  29. BMJ Open. 2013 Nov 07;3(11):e003135 [PMID: 24202053]

Word Cloud

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