Skip to main content
SpringerLink
Log in

Statin pretreatment may increase the risk of symptomatic intracranial haemorrhage in thrombolysis for ischemic stroke: results from a case–control study and a meta-analysis

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

The influence of statins on the results of intravenous thrombolysis for ischemic stroke is controversial. We studied the risks and benefits of statin pretreatment (SP) in patients treated with intravenous alteplase (t-PA) at our institution, and included our data to a meta-analysis of previous related studies. We reviewed prospectively collected data from consecutive patients with acute ischemic stroke treated with IV rt-PA at our institution over the past 9 years. We compared symptomatic intracranial haemorrhage (SICH), favourable short-term outcome (decrease of ≥4 points on the NIHSS score after 24 h from baseline assessment), favourable long-term outcome (mRS score ≤2 at 3 months) and mortality rates between statin-pretreated (SPP) and nonstatin-pretreated patients (NSPP). We performed a systematic search through MEDLINE/PubMed and Embase datasets to identify similar English language studies. A total of 182 patients were included (mean age 68.3 ± 11.4 years, 54.3% men). There were no significant differences between SPP and NSPP regarding SICH (3.3 vs. 1.7%, p = 0.47), favourable short-term outcome (44.8 vs 56%, p = 0.31) and favourable long-term outcome rates (40 vs 44.1%, p = 0.84). In a meta-analysis of 1,055 patients, SP was neither related to long-term functional outcome nor mortality, but it was a risk factor for SICH (OR 1.99, 95% CI 1.03–3.84, p = 0.04). Statin pretreatment may increase the risk of SICH in patients receiving IV t-PA for ischemic stroke, though it does not influence the 3 months outcome. Prospective studies are needed to confirm this safety concern.

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.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333(24):1581–1587

    Google Scholar 

  2. Hacke W et al (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359(13):1317–1329

    Article  PubMed  CAS  Google Scholar 

  3. Marti-Fabregas J et al (2007) Frequency and predictors of symptomatic intracerebral hemorrhage in patients with ischemic stroke treated with recombinant tissue plasminogen activator outside clinical trials. Cerebrovasc Dis 23(2–3):85–90

    PubMed  CAS  Google Scholar 

  4. Wahlgren N et al (2007) Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 369(9558):275–282

    Article  PubMed  CAS  Google Scholar 

  5. Waters DD et al (2006) Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT (treating to new targets) study. J Am Coll Cardiol 48(9):1793–1799

    Article  PubMed  CAS  Google Scholar 

  6. Amarenco P et al (2006) High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 355(6):549–559

    Article  PubMed  CAS  Google Scholar 

  7. Sironi L et al (2003) Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage. Arterioscler Thromb Vasc Biol 23(2):322–327

    Article  PubMed  CAS  Google Scholar 

  8. Chen J et al (2003) Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann Neurol 53(6):743–751

    Article  PubMed  CAS  Google Scholar 

  9. Marti-Fabregas J et al (2004) Favorable outcome of ischemic stroke in patients pretreated with statins. Stroke 35(5):1117–1121

    Article  PubMed  CAS  Google Scholar 

  10. Reeves MJ et al (2008) Effect of pretreatment with statins on ischemic stroke outcomes. Stroke 39(6):1779–1785

    Article  PubMed  CAS  Google Scholar 

  11. Martinez-Sanchez P et al (2009) The beneficial effect of statins treatment by stroke subtype. Eur J Neurol 16(1):127–133

    Article  PubMed  CAS  Google Scholar 

  12. Giroud M et al (1995) Risk factors for primary cerebral hemorrhage: a population-based study—the Stroke Registry of Dijon. Neuroepidemiology 14(1):20–26

    Article  PubMed  CAS  Google Scholar 

  13. Alvarez-Sabin J et al (2007) Prior statin use may be associated with improved stroke outcome after tissue plasminogen activator. Stroke 38(3):1076–1078

    Article  PubMed  CAS  Google Scholar 

  14. Uyttenboogaart M et al (2008) Lipid profile, statin use, and outcome after intravenous thrombolysis for acute ischaemic stroke. J Neurol 255(6):875–880

    Article  PubMed  CAS  Google Scholar 

  15. Miedema I et al (2010) Statin use and functional outcome after tissue plasminogen activator treatment in acute ischaemic stroke. Cerebrovasc Dis 29(3):263–267

    Google Scholar 

  16. Meier N et al (2009) Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke. Stroke 40(5):1729–1737

    Article  PubMed  CAS  Google Scholar 

  17. Hacke W et al (1998) Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European–Australasian Acute Stroke Study Investigators. Lancet 352(9136):1245–1251

    Article  PubMed  CAS  Google Scholar 

  18. Hacke W et al (1995) Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 274(13):1017–1025

    Article  PubMed  CAS  Google Scholar 

  19. Stroup DF et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. J Am Med Assoc 283(15):2008–2012

    Article  CAS  Google Scholar 

  20. Zheng Z, Chen B (2007) Effects of Pravastatin on neuroprotection and neurogenesis after cerebral ischemia in rats. Neurosci Bull 23(4):189–197

    PubMed  CAS  Google Scholar 

  21. Blanco M et al (2007) Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology 69(9):904–910

    Article  PubMed  CAS  Google Scholar 

  22. Byington RP et al (2001) Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Circulation 103(3):387–392

    PubMed  CAS  Google Scholar 

  23. Goldstein LB et al (2008) Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology 70(24 Pt 2):2364–2370

    Article  PubMed  CAS  Google Scholar 

  24. Gaddam V, Li DY, Mehta JL (2002) Anti-thrombotic effects of atorvastatin—an effect unrelated to lipid lowering. J Cardiovasc Pharmacol Ther 7(4):247–253

    Article  PubMed  CAS  Google Scholar 

  25. Gomis M et al (2010) Outcome of intracerebral haemorrhage patients pre-treated with statins. Eur J Neurol 17(3):443–448

    Article  PubMed  CAS  Google Scholar 

  26. Diedler J et al (2010) Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset. Stroke J Cereb Circ 41(2):288–294

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Dr. Martinez-Ramirez is under a research program funded by the Instituto Carlos III (Spanish Ministry of Health) through “Ayuda Rio Hortega”. We thank Anand Viswanathan (MD, PhD) for his help with the manuscript.

Conflicts of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Neurology Department, Hospital de la Santa Creu i Sant Pau, 167 Sant Antoni Maria Claret st., 08025, Barcelona, Spain

    Sergi Martinez-Ramirez, Raquel Delgado-Mederos, Rebeca Marín, Marc Suárez-Calvet, María Pilar Sáinz, Aída Alejaldre, Ángela Vidal-Jordana, Josep Lluís Martí-Vilalta & Joan Martí-Fàbregas

Authors
  1. Sergi Martinez-Ramirez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raquel Delgado-Mederos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebeca Marín
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marc Suárez-Calvet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María Pilar Sáinz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aída Alejaldre
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ángela Vidal-Jordana
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Josep Lluís Martí-Vilalta
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joan Martí-Fàbregas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sergi Martinez-Ramirez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martinez-Ramirez, S., Delgado-Mederos, R., Marín, R. et al. Statin pretreatment may increase the risk of symptomatic intracranial haemorrhage in thrombolysis for ischemic stroke: results from a case–control study and a meta-analysis. J Neurol 259, 111–118 (2012). https://doi.org/10.1007/s00415-011-6137-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-011-6137-3

Keywords

Search

Navigation