Display options
Share it on

Clin Epidemiol. 2015 Aug 24;7:381-9. doi: 10.2147/CLEP.S85427. eCollection 2015.

The impact of preadmission oral bisphosphonate use on 30-day mortality following stroke: a population-based cohort study of 100,043 patients.

Clinical epidemiology

Diana Hedevang Christensen, Erzsébet Horváth-Puhó, Morten Schmidt, Christian Fynbo Christiansen, Lars Pedersen, Bente Lomholt Langdahl, Reimar Wernich Thomsen

Affiliations

  1. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark ; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
  2. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
  3. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.

PMID: 26346502 PMCID: PMC4554427 DOI: 10.2147/CLEP.S85427

Abstract

PURPOSE: Bisphosphonate use has been associated with increased risk of fatal stroke. We examined the association between preadmission use of oral bisphosphonates and 30-day mortality following hospitalization for stroke.

PATIENTS AND METHODS: We conducted a nationwide population-based cohort study using medical databases and identified all patients in Denmark with a first-time hospitalization for stroke between 1 July 2004 and 31 December 2012 (N=100,043). Cox regression was used to compute adjusted hazard ratios as a measure of 30-day mortality rate ratios (MRRs) associated with bisphosphonate current use (prescription filled within 90 days prior to the stroke) or recent use (prescription filled in the 90-180 days prior to the stroke). Current use was further classified as new or long-term use.

RESULTS: We found 51,982 patients with acute ischemic stroke (AIS), 11,779 with intracerebral hemorrhage (ICH), 4,528 with subarachnoid hemorrhage (SAH), and 31,754 with unspecified stroke. Absolute 30-day mortality risks were increased among current vs nonusers of bisphosphonates for AIS (11.9% vs 8.5%), ICH (43.2% vs 34.5%), SAH (40.3% vs 23.2%), and unspecified strokes (18.8% vs 14.0%). However, in adjusted analyses, current bisphosphonate use did not increase 30-day mortality from AIS (MRR, 0.87; 95% confidence interval [CI]: 0.75, 1.01); ICH (MRR, 1.05; 95% CI: 0.90, 1.23); SAH (MRR, 1.15; 95% CI: 0.83, 1.61); or unspecified stroke (MRR, 0.94; 95% CI: 0.81, 1.09). Likewise, no association with mortality was found for recent use. Adjusted analyses by type of bisphosphonate showed increased mortality following stroke among new users of etidronate (MRR, 1.40; 95% CI: 1.01, 1.93) and reduced mortality after AIS among current users of alendronate (MRR, 0.87; 95% CI: 0.74, 1.02).

CONCLUSION: We found no overall evidence that preadmission bisphosphonate use increases 30-day mortality following stroke.

Keywords: cardiovascular disease; mortality; oral bisphosphonates; osteoporosis treatment; prognosis; stroke

References

  1. Neurology. 2014 Nov 25;83(22):2013-22 - PubMed
  2. J Thorac Cardiovasc Surg. 2007 Nov;134(5):1128-35 - PubMed
  3. Rheumatology (Oxford). 2014 Jan;53(1):19-31 - PubMed
  4. Clin Drug Investig. 2006;26(4):215-22 - PubMed
  5. Osteoporos Int. 2014 May;25(5):1617-23 - PubMed
  6. Stroke. 2002 Oct;33(10):2357-62 - PubMed
  7. Eur Neurol. 2009;62(4):212-8 - PubMed
  8. Neurology. 2010 May 11;74(19):1494-501 - PubMed
  9. N Engl J Med. 2007 May 3;356(18):1809-22 - PubMed
  10. Am J Epidemiol. 2003 Nov 1;158(9):915-20 - PubMed
  11. Ther Adv Drug Saf. 2013 Oct;4(5):199-210 - PubMed
  12. J Clin Oncol. 2010 Nov 20;28(33):4898-905 - PubMed
  13. Osteoporos Int. 2011 Jun;22(6):1773-9 - PubMed
  14. Lancet Neurol. 2010 Feb;9(2):167-76 - PubMed
  15. Clin Sci (Lond). 2014 Mar;126(5):339-46 - PubMed
  16. Am J Cardiovasc Drugs. 2010;10(6):359-67 - PubMed
  17. Osteoporos Int. 2011 Apr;22(4):1037-45 - PubMed
  18. Drug Saf. 2009;32(3):219-28 - PubMed
  19. Clin Epidemiol. 2012;4:303-13 - PubMed
  20. Eur J Neurol. 2013 Jan;20(1):57-61 - PubMed
  21. Stroke. 2011 Oct;42(10):2806-12 - PubMed
  22. Am J Cardiovasc Drugs. 2012 Apr 1;12(2):105-16 - PubMed
  23. Osteoporos Int. 2012 Oct;23(10):2551-7 - PubMed
  24. J Transl Med. 2009 Nov 17;7:97 - PubMed
  25. Stroke. 2003 Aug;34(8):1828-32 - PubMed
  26. Stroke. 1996 Mar;27(3):421-4 - PubMed
  27. J Bone Miner Res. 2012 Feb;27(2):243-54 - PubMed
  28. Int J Cardiol. 2013 Jun 20;166(2):385-93 - PubMed
  29. Neurology. 2014 Jan 28;82(4):340-50 - PubMed
  30. Circulation. 2013 Jun 11;127(23):2327-35 - PubMed
  31. Eur J Epidemiol. 2014 Aug;29(8):541-9 - PubMed
  32. Osteoporos Int. 2012 Feb;23 Suppl 1:S1-23 - PubMed
  33. Clin Ther. 2011 Sep;33(9):1173-9 - PubMed
  34. Stroke. 2008 Aug;39(8):2318-24 - PubMed
  35. Am J Kidney Dis. 2004 Oct;44(4):680-8 - PubMed
  36. N Engl J Med. 2007 Aug 16;357(7):712-3; author reply 714-5 - PubMed
  37. Stroke. 2006 Jan;37(1):243-5 - PubMed
  38. J Intern Med. 2009 May;265(5):581-92 - PubMed
  39. J Clin Endocrinol Metab. 2000 Aug;85(8):2793-6 - PubMed
  40. Osteoporos Int. 2009 Oct;20(10):1633-50 - PubMed
  41. Am J Epidemiol. 2006 Jun 15;163(12):1149-56 - PubMed
  42. Chest. 2013 Oct;144(4):1311-22 - PubMed
  43. Osteoporos Int. 2005 Feb;16(2):184-90 - PubMed
  44. Neurology. 2008 Aug 26;71(9):650-5 - PubMed
  45. Am J Med. 2000 Jan;108(1):36-40 - PubMed
  46. Adv Exp Med Biol. 2010;658:11-20 - PubMed
  47. In Vivo. 2013 Nov-Dec;27(6):669-84 - PubMed
  48. Gen Pharmacol. 2000 Dec;35(6):287-96 - PubMed
  49. Scand J Public Health. 2011 Jul;39(7 Suppl):30-3 - PubMed
  50. Neuroepidemiology. 2007;28(3):150-4 - PubMed
  51. Osteoporos Int. 2007 Aug;18(8):1023-31 - PubMed
  52. World Neurosurg. 2011 Dec;76(6 Suppl):S85-90 - PubMed
  53. N Engl J Med. 2007 Nov 1;357(18):1799-809 - PubMed

Publication Types