Journal of Neurology

, Volume 253, Issue 11, pp 1478–1483 | Cite as

Use of calcium channel blockers after stroke is not associated with poor outcome

A cohort from the registry of the Canadian stroke network
  • Dar Dowlatshahi
  • Jiming Fang
  • Marc Kawaja
  • Antoine Hakim



Control of hypertension is essential for the secondary prevention of stroke. Although several trials have assessed the role of calcium channel blockers (CCBs) in the acute stroke, few address their safety and efficacy in secondary prevention. The recovery process after stroke requires neurite outgrowth, which may be dependent on activation of calcium channels and NMDA receptors. We asked whether treatment of hypertension using CCBs is safe during the recovery of patients following stroke and whether it contributes to their functional outcome.


The Registry of the Canadian Stroke Network provided access to information from 1545 patients with ischemic stroke. Primary outcome variables were mortality and functional outcome, which was assessed using the Stroke Impact Scale-16.


Patients discharged on CCB had a 2.5% 6-month mortality rate compared with 5.5% in those who were not on CCB at discharge (OR 0.38, 95% CI 0.17−0.88). There was no change in 6-month mortality with respect to treatment with ACE-I, B-blockers or diuretics at discharge. Patients that were admitted on CCB had improved SIS-16 at 6-months if they were also discharged on CCB, as compared with patients who had their CCB discontinued (73.8 veas 66.8, p = 0.032).


CCB treatment at the time of discharge did not impede functional recovery, and was associated with reduced mortality and improved SIS-16 at 6 months.


stroke calcium channel blockers mortality recovery treatment 


Acknowledgments & Funding

We thank the Canadian Stroke Network, Registry of the Canadian Stroke Network, Institute for Clinical Evaluative Sciences, Kevin Willis and Moira Kapral for access to the Registry cohort, as well as assistance with the design of the study and review of the manuscript.


  1. 1.
    Ahmed N, Nasman P, Wahlgren NG. (2000) Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke 31:1250–1255PubMedGoogle Scholar
  2. 2.
    Angeli F, Verdecchia P, Reboldi GP, Gattobigio R, Bentivoglio M, Staessen JA, Porcellati C. (2004) Calcium channel blockade to prevent stroke in hypertension: a meta-analysis of 13 studies with 103,793 subjects. Am J Hypertens 17:817–822PubMedGoogle Scholar
  3. 3.
    Ciccolini F, Collins TJ, Sudhoelter J, Lipp P, Berridge MJ, Bootman M. D. (2003) Local and global spontaneous calcium events regulate neurite outgrowth and onset of GABAergic phenotype during neural precursor differentiation. J Neurosci 23:103–111PubMedGoogle Scholar
  4. 4.
    Dahlof B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester P. O. (1991) Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 338:1281–1285CrossRefPubMedGoogle Scholar
  5. 5.
    Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, Norris J. (2000) Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31:347–354PubMedGoogle Scholar
  6. 6.
    Diener HC, AlKhedr A, Busse O, Hacke W, Zingmark PH, Jonsson N, Basun H. (2002) Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR. A safety and tolerability study. J Neurol 249:561–568CrossRefPubMedGoogle Scholar
  7. 7.
    Duncan PW, Lai SM, Bode RK, Perera S, DeRosa J. (2003) Stroke Impact Scale-16: A brief assessment of physical function. Neurology 60:291–296CrossRefPubMedGoogle Scholar
  8. 8.
    Duncan PW, Lai SM, Tyler D, Perera S, Reker DM, Studenski S. (2002) Evaluation of proxy responses to the Stroke Impact Scale. Stroke 33:2593–2599CrossRefPubMedGoogle Scholar
  9. 9.
    Edwards B, O’Connell B. (2003) Internal consistency and validity of the Stroke Impact Scale 2.0 (SIS 2.0) and SIS-16 in an Australian sample. Qual Life Res 12:1127–1135CrossRefPubMedGoogle Scholar
  10. 10.
    Gueyffier F, Boissel JP, Boutitie F, Pocock S, Coope J, Cutler J, Ekbom T, Fagard R, Friedman L, Kerlikowske K, Perry M, Prineas R, Schron E. (1997) Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators. Stroke 28:2557–2562PubMedGoogle Scholar
  11. 11.
    Hardingham GE, Fukunaga Y, Bading H. (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci. 5:405–414PubMedGoogle Scholar
  12. 12.
    Horn J, de Haan RJ, Vermeulen M, Limburg M. (2001) Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial. Stroke 32:461–465PubMedGoogle Scholar
  13. 13.
    Horn, J. and Limburg, M. (2000) Calcium antagonists for acute ischemic stroke. Cochrane.Database.Syst.Rev. CD001928–Google Scholar
  14. 14.
    Lai SM, Perera S, Duncan PW, Bode R. (2003) Physical and social functioning after stroke: comparison of the Stroke Impact Scale and Short Form-36. Stroke 34:488–493CrossRefPubMedGoogle Scholar
  15. 15.
    Medical Research Working Party (1985) MRC trial of treatment of mild hypertension: principal results. BMJ (Clin Res Ed) 291:97–104CrossRefGoogle Scholar
  16. 16.
    MRC Working Party (1992) Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ 304:405–412CrossRefGoogle Scholar
  17. 17.
    Pisani A, Calabresi P, Tozzi A, D’Angelo V, Bernardi G. (1998) L-type Ca2+ channel blockers attenuate electrical changes and Ca2+ rise induced by oxygen/glucose deprivation in cortical neurons. Stroke 29:196–201PubMedGoogle Scholar
  18. 18.
    SHEP Cooperative Research Group (1991) Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 265:3255–3264CrossRefGoogle Scholar
  19. 19.
    Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O’Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. (1997) Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 350:757–764CrossRefPubMedGoogle Scholar
  20. 20.
    Steen PA, Gisvold SE, Milde JH, Newberg LA, Scheithauer BW, Lanier WL, Michenfelder J. D. (1985) Nimodipine improves outcome when given after complete cerebral ischemia in primates. Anesthesiology 62:406–414CrossRefPubMedGoogle Scholar
  21. 21.
    The American Nimodipine Study Group (1992) Clinical trial of nimodipine in acute ischemic stroke. Stroke 23:3–8Google Scholar
  22. 22.
    Trust Study Group (1990) Randomised, double-blind, placebo-controlled trial of nimodipine in acute stroke. Lancet 336:1205–1209CrossRefGoogle Scholar
  23. 23.
    Tu JV, Willison DJ, Silver FL, Fang J, Richards JA, Laupacis A, Kapral M. K. (2004) Impracticability of informed consent in the Registry of the Canadian Stroke Network. N Engl J Med 350:1414–1421CrossRefPubMedGoogle Scholar
  24. 24.
    Uematsu D, Greenberg JH, Reivich M, Hickey W. F. (1989) Direct evidence for calcium-induced ischemic and reperfusion injury. Ann Neurol 26:280–283CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2006

Authors and Affiliations

  • Dar Dowlatshahi
    • 1
  • Jiming Fang
    • 2
  • Marc Kawaja
    • 3
  • Antoine Hakim
    • 4
  1. 1.Division of NeurologyOttawa HospitalOttawaCanada
  2. 2.Institute for Clinical Evaluative SciencesTorontoCanada
  3. 3.Dept. of Clinical EpidemiologyMemorial University of NewfoundlandCanada
  4. 4.Ottawa Health Research InstituteUniversity of Ottawa, Canadian Stroke NetworkOttawaCanada

Personalised recommendations