Skip to main content

Advertisement

SpringerLink
Log in

Timing of Blood Pressure Lowering in Acute Ischemic Stroke

  • Cardiovascular Disease and Stroke (S Prabhakaran, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Whether there are any benefits without harm from early lowering of blood pressure (BP) in the setting of acute ischemic stroke (AIS) has been a longstanding controversy in medicine. Whilst most studies have consistently shown associations between elevated BP, particularly systolic BP, and poor outcome, some also report that very low BP (systolic <130 mmHg) and large reductions in systolic BP are associated with poor outcomes in AIS. However, despite these associations, the observed U- or J-shaped relationship between BP and outcome in these patients may not be causally related. Patients with more severe strokes may have a more prominent autonomic response and later lower BP as their condition worsens, often pre-terminally. Fortunately, substantial progress has been made in recent years with new evidence arising from well-conducted randomized trials. This review outlines new evidence and recommendations for clinical practice over BP management in AIS.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Qureshi AI, Ezzeddine MA, Nasar A, Suri MF, Kirmani JF. Hussein. Prevalence of elevated blood pressure in 563,704 adult patients with stroke presenting to the ED in the United States. Am J Emerg Med. 2007;25:32–8.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Qureshi AI. Acute hypertensive response in patients with stroke: pathophysiology and management. Circulation. 2008;118:176–87.

  3. Leonardi-Bee J, Bath PMW, Phillips SJ, Sandercock PAG, for the IST Collaborative Group. Blood pressure and clinical outcomes in the international stroke trial. Stroke. 2002;33:1315–20.

  4. Alqadri SL, Sreenivasan V, Qureshi AI. Acute hypertensive response management in patients with acute stroke. Curr Cardiol Rep. 2013;15:426.

    Article  PubMed  Google Scholar 

  5. Oppenheimer S. The anatomy and physiology of cortical mechanisms of cardiac control. Stroke. 1993;24(12 Suppl):I3–5.

    CAS  PubMed  Google Scholar 

  6. Nason MW, Mason P. Modulation of sympathetic and somatomotor function by the ventromedial medulla. J Neurophysiol. 2004;92:510–22.

    Article  PubMed  Google Scholar 

  7. Meyer JS, Stoica E, Pascu I, et al. Catecholamine concentrations in CSF and plasma of patients with cerebral infarction and haemorrhage. Brain. 1973;96:277–88.

    Article  CAS  PubMed  Google Scholar 

  8. Robinson TG, James M, Youde J, et al. Cardiac baroreceptor sensitivity is impaired after acute stroke. Stroke. 1997;28:1671–6.

    Article  CAS  PubMed  Google Scholar 

  9. Owens WB. Blood pressure control in acute cerebrovascular disease. J Clin Hypertens. 2011;13:205–11.

    Article  Google Scholar 

  10. Willmot M, Leonardi-Bee J, Bath PMW. High blood pressure in acute stroke and subsequent outcome: a systematic review. Hypertension. 2004;43:18–24.

  11. Potter JF, Robinson TG, Ford GA, et al. Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial. Lancet Neurol. 2009;8:48–56.

    Article  CAS  PubMed  Google Scholar 

  12. Diener H-C, Sacco RL, Yusuf S, the Steering Committee and PRoFESS Study Group. Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic, regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the prevention regimen for effectively avoiding second strokes trial (PRoFESS). Cerebrovascular Dis. 2007;23:368–80.

    Article  CAS  Google Scholar 

  13. Bath PMW, Martin RH, Palesch Y, et al. Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis. Stroke. 2009;40:3541–6.

    Article  CAS  PubMed  Google Scholar 

  14. Robinson TG, Potter JF, Ford GA, et al. Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial. Lancet Neurol. 2010;9:767–75.

    Article  CAS  PubMed  Google Scholar 

  15. Sandset EC, Bath PM, Boysen G, et al. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet. 2011;377:741–50.

  16. Sandset EC, Murray GD, Bath PM, et al. Relation between change in blood pressure in acute stroke and risk of early adverse events and poor outcome. Stroke. 2012;43:2108–14.

    Article  PubMed  Google Scholar 

  17. He J, Zhang Y, Xu T, et al. Effects of immediate blood pressure reduction on death and major disability in patients with acute ischemic stroke: the CATIS randomized clinical trial. JAMA. 2014;311:479–89. Large-scale Chinese randomised trial showing neutral effects of modest blood pressure lowering using oral antihypertensive agents in mainly mild severity acute ischemic stroke.

    Article  CAS  PubMed  Google Scholar 

  18. Saver JL, Starkman S, Eckstein M, et al. Prehospital use of magnesium sulfate as neuroprotection in acute stroke. New Engl J Med. 2015;372:528–36.

    Article  CAS  PubMed  Google Scholar 

  19. The ENOS Investigators. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial. Lancet. 2015;385:617–28. Landmark large-scale international randomised trial of use of nitrate patch to lower blood pressure and provide potential neuroprotection, showing no overall effects in acute stroke. However, subgroup analysis indicates potential treatment effect when applied within 6 hours of stroke onset.

    Article  Google Scholar 

  20. Ankolekar S, Fuller M, Cross I, et al. Feasibility of an ambulance-based stroke trial, and safety of glyceryl trinitrate in ultra-acute stroke: the rapid intervention with glyceryl trinitrate in Hypertensive Stroke Trial (RIGHT, ISRCTN66434824). Stroke. 2013;44:3120–28.

    Article  CAS  PubMed  Google Scholar 

  21. Wang H, Tang Y, Rong X, et al. Effects of early blood pressure lowering on early and long-term outcomes after acute stroke: an updated meta-analysis. PLoS One. 2014;9:e97917.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Bath PMW, Krishnan K. Interventions for deliberately altering blood pressure in acute stroke. Cochrane Database Syst Rev. 2014;Issue 10. Art. No.: CD000039. doi: 10.1002/14651858.CD000039.pub3. Cochrane Library Systematic Overview of randomised evidence of blood pressure lowering in acute stroke. Some evidence of time relationship of treatment benefit.

  23. Wahlgren N, Ahmed N, Eriksson N, et al. Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: safe Implementation of thrombolysis in stroke-mOnitoring study (SITS-MOST). Stroke. 2008;39:3316–22.

    Article  PubMed  Google Scholar 

  24. Ahmed N, Wahlgren N, Brainin M, et al. Relationship of blood pressure, antihypertensive therapy, and outcome in ischemic stroke treated with intravenous thrombolysis: retrospective analysis from safe implementation of Thrombolysis in stroke-international stroke Thrombolysis register (SITS-ISTR). Stroke. 2009;40:2442–9.

  25. Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368:2355–65. Pivotal international randomized trial showing safety and benefits on functional outcome of early intensive blood pressure lowering in acute intracerebral haemorrhage.

    Article  CAS  PubMed  Google Scholar 

  26. Tsivgoulis G, Katsanos AH, Butcher KS, et al. Intensive blood pressure reduction in acute intracerebral haemorrhage: a meta-analysis. Neurology. 2014;83:1523–9.

    Article  PubMed  Google Scholar 

  27. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384:1929–35. Individual patient data meta-analysis of trials of thrombolysis in acute ischemic stroke.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Shamy MC, Jaigobin CS. The complexities of acute stroke decision-making: a survey of neurologists. Neurology. 2013;81:1–4.

    Article  Google Scholar 

  29. Brown SG, MacDonald SP, Hankey GJ. Do risks outweight benefits in thrombolysis for stroke? BMJ. 2013;347:f5215.

    Article  PubMed  Google Scholar 

  30. Anderson C. Enhanced control of hypertension and thrombolysis stroke study (ENCHANTED) [cited 2014 29 September]; Available from: http://clinicaltrials.gov/ct2/show/record/NCT01422616.

  31. Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke. 2013;44:870–947.

    Article  PubMed  Google Scholar 

  32. The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329:673–82.

    Article  Google Scholar 

  33. the TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction: results of the thrombolysis in myocradial infarction (TIMI) phase II trial. N Engl J Med. 1989;320:618–27.

    Article  Google Scholar 

  34. Tsai JP, Rochon PA, Raptis S, et al. A prescription at discharge improves long-term adherence for secondary stroke prevention. J Stroke Cerebrovasc Dis. 2014;23(9):2038–15.

    Article  Google Scholar 

  35. Ovbiagele B, Saver JL, Fredieu A, et al. In-hospital initiation of secondary stroke prevention therapies yields high rates of adherence at follow-up. Stroke. 2004;35(12):2879–83.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

C Carcel declares no conflicts of interest. CS Anderson is the Principal Investigator investigating early intensive blood pressure lowering in acute intracerebral hemorrhage (INTERACT trials) and ischemic stroke (ENCHANTED trial) which have received project grant funding from the National Health and Medical Research Council (NHMRC) of Australia.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

Author information

Authors and Affiliations

  1. The George Institute for Global Health, Sydney, Australia

    Cheryl Carcel & Craig S. Anderson

  2. Royal Prince Alfred Hospital, Sydney, Australia

    Cheryl Carcel & Craig S. Anderson

  3. University of Sydney, Sydney, Australia

    Cheryl Carcel & Craig S. Anderson

Authors
  1. Cheryl Carcel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Craig S. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Craig S. Anderson.

Additional information

This article is part of the Topical Collection on Cardiovascular Disease and Stroke

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carcel, C., Anderson, C.S. Timing of Blood Pressure Lowering in Acute Ischemic Stroke. Curr Atheroscler Rep 17, 42 (2015). https://doi.org/10.1007/s11883-015-0520-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-015-0520-y

Keywords

Search

Navigation