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Prior Statin Use Reduces Mortality in Intracerebral Hemorrhage

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Abstract

Objective

To assess the impact of blood glucose, coagulopathy, seizures and prior statin and aspirin use on clinical outcome following intracerebral hemorrhage (ICH).

Background

Intracerebral hemorrhage (ICH) accounts for 10–15% of all strokes with mortality rates approaching 50%. Glasgow Coma Scale (GCS), ICH volume, age, pulse pressure, ICH location, intraventricular hemorrhage (IVH) and hydrocephalus are known to impact 30-day survival following ICH and are included in various prediction models. The role of other clinical variables in the long-term outcome of these patients is less clear.

Methods

Records of consecutive ICH patients admitted to The Johns Hopkins Hospital from 1999 to 2006 were reviewed. Patients with ICH related to trauma or underlying lesions (e.g. brain tumors, aneurysms, arterio-venous malformations) and of infratentorial location were excluded. The impact of admission blood glucose, coagulopathy, seizures on presentation and prior statin and aspirin use on 30-day mortality and functional outcomes at discharge was assessed using dichotomized Modified Rankin Scale (dMRS) and Glasgow Outcomes scale (dGOS). Other variables known to impact outcomes that were included in the multiple logistic regression analysis were age, admission GCS, pulse pressure, ICH volume, ICH location, volume of IVH and hydrocephalus.

Results

A total of 314 patients with ICH were identified, 125 met inclusion criteria. Patients’ age ranged from 34 to 90 years (mean 63.5), 57.6 % were male. Mean ICH volume was 32.09 cc (range 1–214 cc). Following multiple logistic regression analysis, prior statin use (P = 0.05) was found to be associated with decreased mortality with a greater than 12-fold odds of survival while admission blood glucose (P = 0.023) was associated with increased 30-day mortality. Coagulopathy, seizures on presentation, and prior aspirin use had no significant impact on 30-day mortality or outcomes at discharge in our study cohort.

Conclusions

The significant association of prior statin use with decreased mortality warrants prospective evaluation of the use of statins following ICH.

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References

  1. Broderick J, Brott T, Tomsick T, Miller R, Huster G. Intracerebral hemorrhage is more than twice as common as subarachnoid hemorrhage. J Neurosurg 1993;78:188–91.

    PubMed  CAS  Google Scholar 

  2. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med 2001;344:1450–60.

    Article  PubMed  CAS  Google Scholar 

  3. Broderick JP, Adams HP Jr, Barsan W et al. Guidelines for the management for spontaneous intracerebral hemorrhage. Statement for healthcare professionals from a special writing group of the Stroke Council AHA. Stroke 1999;30:905–15.

    PubMed  CAS  Google Scholar 

  4. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993; 24:987–93.

    PubMed  CAS  Google Scholar 

  5. Tuhrim S, Dambrosia JM, Price TR, Mohr JP, Wolf PA, Heyman A, Kase CS. Prediction of intracerebral hemorrhage survival. Ann Neurol 1988;24(2):258–63.

    Article  PubMed  CAS  Google Scholar 

  6. Tuhrim S, Horowitz DR, Sacher M, Godbold JH. Validation and comparison of models predicting survival following intracerebral hemorrhage. Crit Care Med 1995;23(5):950–4.

    Article  PubMed  CAS  Google Scholar 

  7. Hemphill JC III, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001;32(4):891–7.

    PubMed  Google Scholar 

  8. Clarke JL, Johnston SC, Farrant M, Bernstein R, Tong D, Hemphill JC III. External validation of the ICH score. Neurocrit Care 2004;1(1):53–60.

    Article  PubMed  Google Scholar 

  9. Cheung RT, Zou LY. Use of the original, modified, or new intracerebral hemorrhage score to predict mortality and morbidity after intracerebral hemorrhage. Stroke 2003;34(7):1717–22.

    Article  PubMed  Google Scholar 

  10. Song EC, Chu K, Jeong SW, Jung KH, Kim SH, Kim M, Yoon BW. Hyperglycemia exacerbates brain edema and perihematomal cell death after intracerebral hemorrhage. Stroke 2003;34(9):2215–20.

    Article  PubMed  CAS  Google Scholar 

  11. Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology 2003;61(10):1351–6.

    PubMed  Google Scholar 

  12. Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004;63(6):1059–64.

    PubMed  CAS  Google Scholar 

  13. Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004;164(8):880–4.

    Article  PubMed  CAS  Google Scholar 

  14. Vespa PM, O’Phelan K, Shah M, Mirabelli J, Starkman S, Kidwell C, Saver J, Nuwer MR, Frazee JG, McArthur DA, Martin NA. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology 2003;60(9):1441–6.

    PubMed  CAS  Google Scholar 

  15. Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen ER, Hillbom M. Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death. Stroke 2006; 37(1):4–5.

    Google Scholar 

  16. Seyfried D, Han Y, Lu D, Chen J, Bydon A, Chopp M. Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats. J Neurosurg 2004;101(1):104–7.

    Article  PubMed  CAS  Google Scholar 

  17. Naff NJ, Carhuapoma JR, Williams MA, Bhardwaj A, Ulatowski JA, Bederson J, Bullock R, Schmutzhard E, Pfausler B, Keyl PM, Tuhrim S, Hanley DF. Treatment of intraventricular hemorrhage with urokinase: effects on 30-day survival. Stroke 2000;31(4):841–7.

    PubMed  CAS  Google Scholar 

  18. Steiner L, Bergvall U, Zwetnow N. Quantitative estimation of intracerebral and intraventricular hematoma by computer tomography. Acta Radiol Suppl 1975;346:143–54.

    PubMed  CAS  Google Scholar 

  19. Plehn JF, Davis BR, Sacks FM, Rouleau JL, Pfeffer MA, Bernstein V, Cuddy TE, Moye LA, Piller LB, Rutherford J, Simpson LM, Braunwald E. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The care investigators. Circulation 1999;99(2):216–23.

    PubMed  CAS  Google Scholar 

  20. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–9.

    Article  Google Scholar 

  21. Sacks FM, Pfeffer MA, Moyé LA et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;336:1001–9.

    Article  Google Scholar 

  22. The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349–57.

    Article  Google Scholar 

  23. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.

    Article  Google Scholar 

  24. Amarenco P, Bogousslavsky J, Callahan A III, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA. Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355(6):549–59.

    Article  PubMed  CAS  Google Scholar 

  25. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke 2005;36(8):1627–32.

    Article  PubMed  CAS  Google Scholar 

  26. Lynch JR, Wang H, McGirt MJ, Floyd J, Friedman AH, Coon AL, Blessing R, Alexander MJ, Graffagnino C, Warner DS, Laskowitz DT. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke 2005;36(9):2024–6.

    Article  PubMed  CAS  Google Scholar 

  27. McGirt MJ, Blessing R, Alexander MJ, Nimjee SM, Woodworth GF, Friedman AH, Graffagnino C, Laskowitz DT, Lynch JR. Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: a multivariate analysis of an institutional experience. J Neurosurg 2006;105(5):671–4.

    PubMed  CAS  Google Scholar 

  28. Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996;348:1079–82.

    Article  PubMed  CAS  Google Scholar 

  29. Laufs U, LaFata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998;97:1129–35.

    PubMed  CAS  Google Scholar 

  30. McGirt MJ, Lynch JR, Parra A, Sheng H, Pearlstein RD, Laskowitz DT, Pelligrino DA, Warner DS. Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke 2002;33:2950–6.

    Article  PubMed  CAS  Google Scholar 

  31. Laufs U, Gertz K, Huang P, Nickenig G, Bohm M, Dirnagl U, Endres M. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 2000;31:2437–49.

    Google Scholar 

  32. Miwa Y, Ozaki, Namiki MD, Hirase T, Inoue N, Hirata K, Yokoyama M. Kawashima S, Yamashita T. HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats. Stroke 2003;34:157–63.

    Article  PubMed  Google Scholar 

  33. Hanjani-Amin S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke 2001;32:980–6.

    Google Scholar 

  34. Vaughan CJ, Delanty N. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke 1999;30:1969–73.

    PubMed  CAS  Google Scholar 

  35. Chen J, Zhang ZG, Li Y, Wang Y, Wang L, Jiang H, Zhang C, Lu M, Katakowski M, Feldkamp CS, Chopp M. Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann Neurol 2003;53:743–51.

    Article  PubMed  CAS  Google Scholar 

  36. Jung KH, Chu K, Jeong SW, Han SY, Lee ST, Kim JY, Kim M, Roh JK. HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage. Stroke 2004;35(7):1744–9.

    Article  PubMed  CAS  Google Scholar 

  37. Demchuk AM, Morgenstern LB, Krieger DW, Linda Chi T, Hu W, Wein TH, Hardy RJ, Grotta JC, Buchan AM. Serum glucose and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke 1999;30:34–9.

    PubMed  CAS  Google Scholar 

  38. Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 2005;64(8):1348–53.

    PubMed  Google Scholar 

  39. Gray CS, Hildreth AJ, Sandercock PA, O’Connell JE, Johnston DE, Cartlidge NE, Bamford JM, James OF, Alberti KG. GIST trialists collaboration.Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol 2007;6(5):397–406.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Neeraj S. Naval.

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Naval, N.S., Abdelhak, T.A., Zeballos, P. et al. Prior Statin Use Reduces Mortality in Intracerebral Hemorrhage. Neurocrit Care 8, 6–12 (2008). https://doi.org/10.1007/s12028-007-0080-2

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