In-Hospital Blood Pressure Control After Acute Ischemic Stroke

Stroke remains a leading cause of morbidity and mortality in the US,^1,2 with direct costs of care projected to be over $180 million by year 2030.³ Despite significant advances in ischemic stroke management with the advent of thrombolysis and endovascular treatment, outcomes remain suboptimal. Blood pressure (BP) control plays an important but complex role in outcomes of acute ischemic stroke (AIS). A “U-shaped” relationship between BP and outcomes exists in acute stroke, with both high and low BPs resulting in worse clinical outcomes.^4-6 Here, we review the basic physiologic principles of BP regulation and current practice guidelines for BP management in the setting of AIS.

The Acute Hypertensive Response

Hypertension (HTN) is the most common modifiable risk factor for ischemic stroke,⁷ affecting approximately 45% of adults in the US.⁸ Of those presenting with AIS, 69% to 84% meet criteria for HTN, defined as BP greater than 140/90 mm Hg.^5,9,10 The higher rate of acute HTN is caused by a reactive physiologic phenomenon that increases perfusion to collateral vasculature surrounding acutely ischemic tissue.

Acute BP Management

In Those Eligible for Thrombolysis

Acute stroke triage includes a rapid clinical assessment and physical examination, acquisition of CT imaging, and screening for potential fibrinolytic use. When recombinant tissue plasminogen activator (rt-PA) is considered, current American Heart Association/American Stroke Association (AHA/ASA) guidelines require BP to be less than 185/110 mm Hg prior to initiation of the bolus dose and less than 180/105 mm Hg for 24 hours after administration.¹¹ Attaining these values was associated with a lower incidence of symptomatic intracranial hemorrhage (ICH) in the original dose finding studies of rt-PA and were advanced as the BP threshold for acute stroke using intravenous (IV) thrombolysis.¹²

Multiple antihypertensive drug classes have been studied for AIS, including calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, alpha receptor antagonists, angiotensin receptor antagonists, beta blockers, and nitric oxide donors.¹³ For AIS, BP lowering was most effective in clinical trials utilizing alpha receptor antagonists or nitric oxide donors.¹³ Current guidelines advocate use of clevidipine, enalapril, hydralazine, labetalol, or nicardipine for BP lowering in AIS because of their rapid effect.¹¹ Of note, those selected for IV thrombolysis using advanced imaging techniques for “wake-up” stroke are still subject to similar BP thresholds.¹¹

BP lowering below the current guideline-recommended BP threshold to improve patient outcome has been an active area of research. Most recently, a randomized clinical trial did not show improved 90-day functional outcomes after more aggressive systolic BP (SBP) lowering with a target of 130 to 140 mm Hg in the setting of thrombolysis when compared with the standard-of-care arm of 180 mm Hg.¹⁴ This study, however, was limited by a small difference in attained SBP lower and standard systolic BP arms. Interestingly, less intracerebral hemorrhage was observed in the lower BP arm.

In Those Eligible for Thrombectomy

For people with AIS who also harbor a large vessel occlusion (LVO) stroke about to undergo thrombectomy, guideline-recommended BP goals are the same as for those treated with IV thrombolysis.¹¹ Most recent guidelines suggest that it is reasonable to keep BP at or below 185/110 mm Hg prior to the procedure.¹¹ This BP goal was largely dictated by the BP-based exclusion criteria of recent thrombectomy clinical trials.^15-19 These criteria were set forth after original studies reported that higher SBP at presentation was associated with a higher risk of postthrombectomy hemorrhage.¹⁹ Interestingly, the benefit of thrombectomy compared with medical management was sustained in individuals presenting with higher SBP. It is thus argued that people with LVO stroke otherwise eligible for thrombectomy should be promptly transferred to the neurointervention suite regardless of their preprocedural BP.

Similar to IV thrombolysis, prethrombectomy BP has a “U-shaped” relationship with outcomes, such that significant increases or reductions in BP are associated with worse outcomes.²⁰ Only a few small studies have evaluated induced hypertension in LVO ischemic stroke.^21,22 Of these, 1 study recruited participants with proximal anterior circulation severe stenosis or occlusion and known diffusion-perfusion mismatch exclusively.²¹ Using IV phenylephrine to increase mean arterial pressure (MAP) by 10% to 20% from baseline for 24 hours, a significant benefit was found in National Institute of Health Stroke Scale (NIHSS) scores at day 3 and in cognitive testing.²²

In Those Ineligible for Thrombolysis or Thrombectomy

Patients ineligible for IV thrombolysis are allowed permissive HTN up to 220/120 mm Hg within the first 24 hours of presentation. Multiple randomized clinical trials have not shown a clear benefit for BP reduction with antihypertensives within the first 24 hours,^23,24 and some have even shown worse outcome in the setting of hypotension.⁵ For this reason, new to the 2019 AHA/ASA guidelines is the additional recommendation to reverse any hypotension or hypovolemia.¹¹ This recommendation stems from a study demonstrating an association between low BP at presentation and poor clinical outcomes related to heart failure, sepsis, and gastrointestinal bleeding.²⁵

Postthrombolysis BP Management

Current guidelines recommend a BP target of less than 180/105 mm Hg after thrombolytics.¹¹ Explicit BP monitoring recommendations include BP checks every 15 minutes for the first 2 hours after infusion, followed by every 30 minutes for the next 6 hours, and then hourly until 24 hours posttreatment.¹¹ Refractory or fluctuating BP postthrombolysis is associated with worse outcomes.^26-28 BP variability has been associated with increased risk of any hemorrhage, symptomatic hemorrhage, and mortality following thrombolytic administration.^29-31 Thus, it is important to use antihypertensive medications that are not associated with increased BP variability, such as calcium channel blockers or thiazide diuretics.³²

Postthrombectomy BP Management

Postthrombectomy BP management has been debated. New to the 2019 AHA/ASA guidelines is the recommendation that it may be “reasonable to maintain BP at a level of 180/105 mm Hg or less for at least 24 hours.”¹¹ Many large, observational, multicenter studies confirm higher SBP in the first 24 hours postthrombectomy is associated with worse outcomes and possible with hemorrhagic complications.^33-37 This effect of higher SBP on outcomes is particularly strong amongst those with successful recanalization,^38,39 making it unsurprising that many stroke centers, when accounting for this heterogeneity of reperfusion, often choose BP goals below the recommended guideline.⁴⁰ Whether lower posttrombectomy targets are safe and improve patient-centric outcomes is an active area of research. A recent, randomized, multicenter trial failed to show a lower postthrombectomy SBP target of less than 140 mm Hg improved the rate of any intracerebral hemorrhage compared with a higher target of 185 mm Hg or less.⁴¹

Conclusions and Future Directions

Appropriate BP management for acute ischemic stroke remains somewhat elusive despite multiple large randomized clinical trials. The current AHA/ASA guidelines recommend a BP goal of less than 185/110 mm Hg for patients undergoing IV thrombolysis and a BP goal less than 180/105 mm Hg for the first 24 hours after thrombolytic administration. The same guidelines recommend a BP goal of less than 180/110 mm Hg post thrombectomy and less than 220/120 mm Hg for patients not treated with any acute reperfusion therapy. Determining if modulation of BP beyond these guideline recommended targets before or after acute stroke reperfusion therapies improve outcomes is an active area of research. It is hoped that personalized BP approaches that account for factors such as age, collateral status, and size of vessel occlusion, will be the future of acute and postacute stroke management.