BP Management for Ischemic Stroke in the First 24 Hours

Abstract and Introduction

Abstract

High blood pressure (BP) is common after ischemic stroke and associated with a poor functional outcome and increased mortality. The conundrum then arises on whether to lower BP to improve outcome or whether this will worsen cerebral perfusion due to aberrant cerebral autoregulation. A number of large trials of BP lowering have failed to change outcome whether treatment was started prehospital in the community or hospital. Hence, nuances on how to manage high BP are likely, including whether different interventions are needed for different causes, the type and timing of the drug, how quickly BP is lowered, and the collateral effects of the drug, including on cerebral perfusion and platelets. Specific scenarios are also important, including when to lower BP before, during, and after intravenous thrombolysis and endovascular therapy/thrombectomy, when it may be necessary to raise BP, and when antihypertensive drugs taken before stroke should be restarted. This narrative review addresses these and other questions. Although further large trials are ongoing, it is increasingly likely that there is no simple answer. Different subgroups of patients may need to have their BP lowered (eg, before or after thrombolysis), left alone, or elevated.

Introduction

Managing blood pressure (BP) in the acute phase of ischemic stroke is an important problem in stroke care, with high BP present in 70% of patients. Typical decisions relate to patients needing reperfusion. Guidelines recommend that high BP exceeding 185/110 mm Hg be lowered before thrombolysis^[1,2] but without specifying what drug(s) to use and what target BP should be lowered. Outside of thrombolysis, there is even less certainty. Although the management of BP in acute stroke has been debated since 1985,^[3–5] there has been little advance in our knowledge over the last 35 years despite the completion of numerous randomized controlled clinical trials, almost all of which were neutral or negative for effect on functional outcome. As a result, the management of BP in acute ischemic stroke remains controversial.^[6,7]

Simply lowering BP does not seem to alter outcome in the acute phase of ischemic stroke, and clearly, some nuances need to be considered. First, the causes of high BP are multitudinous and vary between patients.^[8] High BP in the acute stroke setting can be proactive or reactive to the stroke. In this respect, treating hypertension that contributed to the stroke may make more sense than lowering BP that increased in response to the stroke, as occurs with increasing intracranial pressure. Second, antihypertensive drug classes vary in their targets and hormonal and collateral effects, so administering one class may be more appropriate than using another. For example, targeting the renin-angiotensin-aldosterone system may be unhelpful if hypertension is related to sympathetic stimulation. Equally, using β-blockers may be inappropriate in low cardiac output states. Third, timing may be critical; for example, lowering BP in the ultra-acute period may be hazardous while collaterals have not opened adequately, and cerebral perfusion depends on BP. The following review addresses these and other questions in more detail. Where possible, we focus on the results of randomized controlled clinical trials rather than observational studies, which inevitably suffer from indication and other forms of bias. Trials of BP lowering have focused on 2 strategies, either using a specific drug or comparing intensive versus guideline BP targets (Figure). We describe these by following the ABCD approach to lowering BP^[9] and adding other drug classes and target trials. Additional information is given in the Supplemental Material. This is a narrative review, and there are no data for sharing.

(Enlarge Image)

Figure.

Relevant randomized controlled trials of blood pressure lowering in acute stroke.
ACCESS indicates Acute Candesartan Cilexetil Therapy in Stroke Survivors; ACE-I, angiotensin-converting enzyme inhibitor; ARA, angiotensin receptor antagonist; β-RA, beta receptor antagonist; BEST, Blood Pressure After Endovascular Therapy for Ischemic Stroke; CATIS, China Antihypertensive Trial in Acute Ischaemic Stroke; CCB, calcium channel blocker; ENOS, Efficacy of Nitric Oxide in Stroke; ICH, intracerebral hemorrhage; INWEST, Nimodipine West European Stroke Trial; IV, intravenous; MR ASAP, Multicentre Randomized Trial of Acute Stroke Treatment in the Ambulance With a Nitroglycerin Patch; NTG, nitroglycerin/glyceryl trinitrate; RIGHT-2, Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial; and SCAST, Scandinavian Candesartan Acute Stroke Trial.

Authors and Disclosures

Philip M. Bath, DSc, FMedSci, Lili Song, MD, PhD, Gisele S. Silva, MD, PhD, Eva Mistry, MBBS, MSCI, Nils Petersen, MD, MSc, Georgios Tsivgoulis, MD, PhD, Mikael Mazighi, MD, PhD, Oh Young Bang, MD, PhD and Else Charlotte Sandset, MD, PhD

Stroke Trials Unit, Mental Health and Clinical Neuroscience, University of Nottingham, United Kingdom (P.M.B.). Stroke, Nottingham University Hospitals NHS Trust, United Kingdom (P.M.B.). The George Institute China at Peking University Health Science Center, Beijing (L.S.). Faculty of Medicine, George Institute for Global Health, University of New South Wales, Sydney, Australia (L.S.). Neurology, Federal University of São Paulo (UNIFESP) and Hospital Israelita Albert Einstein, Brazil (G.S.S.). Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (E.M.). Department of Neurology, Divisions of Vascular Neurology and Neurocritical Care, Yale School of Medicine, New Haven (N.P.). Second Department of Neurology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece (G.T.). Department of Neurology, Lariboisiere Hospital, and Interventional Neuroradiology, Fondation Rothschild Hospital, University of Paris, INSERM 1148, FHU Neurovasc, France (M.M.). Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (O.Y.B.). Stroke Unit, Department of Neurology, Oslo University Hospital, Norway (E.C.S.). The Norwegian Air Ambulance Foundation, Oslo (E.C.S.).

Correspondence to
Philip Bath, DSc, FMedSci, Stroke Trials Unit, Queen's Medical Centre, University of Nottingham, South Floor, D Floor, Nottingham NG7 2UH, United Kingdom. Email philip.bath@nottingham.ac.uk

Disclosures
P.M. Bath was a member of the Working Group of the European Stroke Organisation Guidelines on Blood Pressure Management in Acute Ischaemic Stroke and Intracerebral Haemorrhage. He receives funding from the Nottingham University Hospitals Trust Charity (chief investigator, ENOS-2 [Efficacy of Nitric Oxide in Stroke-2]) and British Heart Foundation (chief investigator, artificial intelligence project including acute stroke trials) and has received honoraria for consultancy with DiaMedica, Moleac, and Phagenesis (unrelated to this review). Dr Song receives internal funding from The George Institute and funding from Takeda China as co-principal investigator of an ongoing prehospital blood pressure management trial (INTERACT4 [Intensive Ambulance-Delivered Blood Pressure Reduction in Hyper-Acute Stroke Trial]). Dr Silva receives funding from the Brazilian Ministry of Health for the OPTIMAL Stroke trial (Optimal Blood Pressure for the Prevention of Major Vascular Events in Stroke Patients). E. Mistry receives funding from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) as principal investigator of an ongoing randomized trial on blood pressure management after endovascular therapy (BEST-II [Blood Pressure After Endovascular Therapy for Ischemic Stroke II]). Dr Petersen receives funding from the NIH/NINDS as principal investigator of a study on autoregulation-guided blood pressure management after stroke. Dr Tsivgoulis was a co-chair of the Working Group of the European Stroke Organisation Guidelines on Blood Pressure Management in Acute Ischaemic Stroke and Intracerebral Haemorrhage. Dr Mazighi is a principal investigator of the BP-TARGET trial (Safety and Efficacy of Intensive Blood Pressure Lowering After Successful Endovascular Therapy in Acute Ischaemic Stroke). Dr Sandset was chair of the Working Group of the European Stroke Organisation Guidelines on Blood Pressure Management in Acute Ischaemic Stroke and Intracerebral Haemorrhage. The other author reports no conflicts.