The Time Is Brain Review

Personalized Blood Pressure Targeting After Endovascular Therapy for Acute Ischemic Stroke — A Randomized Clinical Trial

· DOI: 10.1001/jamaneurol.2026.1706

stroke deep-dive blood pressure endovascular therapy acute ischemic stroke

Stylized illustration of Personalized Blood Pressure Targeting After Endovascular Therapy for Acute Ischemic Stroke
AI-generated editorial illustration. Generated for editorial use.

Clinical Question (PICO)

In adults with anterior-circulation large-vessel occlusion stroke who achieve successful reperfusion after endovascular therapy (mTICI ≥2b) and were previously functionally independent, does a reperfusion-guided systolic blood-pressure strategy for 72 hours—100–140 mm Hg after mTICI 2c/3 and 140–160 mm Hg after mTICI 2b—improve 90-day functional independence compared with guideline-recommended management (systolic BP ≤180 mm Hg)? Prespecified subgroup analyses examined reperfusion grade and other baseline characteristics.

Bottom Line

In the HOPE multicenter randomized clinical trial, 60.0% of patients assigned to reperfusion-guided BP management versus 47.1% assigned to guideline-recommended management achieved mRS 0–2 at 90 days (absolute risk difference 13.3%, 95% CI 4.1%–22.6%; OR 1.71, 95% CI 1.17–2.50; P=.005). Hemorrhagic transformation was less frequent, while symptomatic intracranial hemorrhage and mortality were similar. The early-stopped, relatively small, highly selected trial supports a tailored rather than uniformly intensive BP strategy, but its authors appropriately describe the result as hypothesis-generating rather than practice-changing.

Design

  • Trial type: Investigator-initiated, phase 3, multicenter, prospective randomized clinical trial; open-label treatment with blinded endpoint assessment (PROBE design)
  • N: 440 in the intention-to-treat analysis (446 randomized; 6 withdrew or were withdrawn)
    • Reperfusion-guided hemodynamic optimization: 215
    • Guideline-recommended standard care: 225
  • Randomization: 1:1 conditional stratified randomization by final reperfusion status (mTICI 2b vs 2c/3) and center
  • Setting: 11 comprehensive stroke centers in Spain
  • Enrollment: June 14, 2021, to October 1, 2025
  • Mean follow-up: 90 days (±15 days)
  • Analysis: Intention-to-treat primary analysis; adjusted and multiple-imputation sensitivity analyses; ordinal mRS shift analysis; prespecified subgroup analysis
  • Primary outcome: Favorable functional outcome, defined as mRS 0–2 at 90 days

Population

Inclusion Criteria

  • Age ≥18 years
  • Prestroke functional independence (mRS 0–2)
  • Acute anterior-circulation ischemic stroke due to large-vessel occlusion, treated within 24 hours of symptom onset
  • Successful endovascular reperfusion, defined as mTICI ≥2b, involving the terminal internal carotid artery, proximal M1/M2 middle cerebral artery, proximal A1 anterior cerebral artery, or a tandem occlusion

Exclusion Criteria

  • ASPECTS <6 or posterior-circulation stroke
  • Congestive heart failure or arterial dissection
  • ≥50% intracranial or extracranial stenosis not successfully revascularized at the end of the procedure
  • Participation in another trial that could interfere with outcome assessment

Baseline Characteristics (overall or representative arm)

  • Mean age 75 years; 53.0% women
  • Median baseline NIHSS 16 (IQR 10–20)
  • Mean admission systolic BP 150 (25) mm Hg; mean pre-randomization systolic BP 138 (23) mm Hg
  • mTICI 2b in 43 patients (9.8%); mTICI 2c/3 in 397 (90.2%)
  • Cardioembolic source in 60.6%; atherosclerotic source in 10.6%; embolic stroke of undetermined source in 25.5%

Interventions

  • Reperfusion-guided hemodynamic optimization: For 72 hours, systolic BP 100–140 mm Hg after mTICI 2c/3 and 140–160 mm Hg after mTICI 2b. Intravenous labetalol or urapidil were first-line antihypertensives; isotonic saline followed by phenylephrine, ephedrine, or norepinephrine could be used for BP augmentation. Monitoring was at least every 30 minutes in the first 24 hours and hourly from 24–72 hours.
  • Guideline-recommended standard care: Systolic BP ≤180 mm Hg for 72 hours, with monitoring at least hourly in the first 24 hours and every 6 hours thereafter. Treatment choices followed local practice.

Outcomes

Primary Outcome (mRS 0–2 at 90 days):

  • Overall, prespecified primary analysis: Favorable outcome in 129/215 (60.0%) with reperfusion-guided management versus 106/225 (47.1%) with standard care; absolute risk difference 13.3% (95% CI 4.1%–22.6%; P=.005); OR 1.71 (95% CI 1.17–2.50). Adjusted sensitivity OR 1.71 (95% CI 1.11–2.63); multiple-imputation OR 1.67 (95% CI 1.14–2.45; P=.008).
  • Ordinal shift analysis: Common OR for a shift toward better mRS scores 1.43 (95% CI 1.03–2.00).
  • Prespecified subgroups: No significant heterogeneity in treatment effect was identified across the prespecified subgroups. The mTICI 2b subgroup was small, and the article reports no clear benefit in that subgroup; the trial was not powered to establish a subgroup-specific effect.

Secondary Outcomes:

  • Mean systolic BP during the first 24 hours after mTICI 2c/3 was 125 (14) mm Hg in the intervention group versus 134 (18) mm Hg in control; between-group difference −9.0 mm Hg (95% CI −12 to −6; P<.001).
  • Among mTICI 2b patients, the corresponding mean difference was +3.0 mm Hg (95% CI −6 to 12; P=.51), consistent with the higher target assigned to incomplete reperfusion.
  • Median time in target was 79% (IQR 63%–92%) in the intervention group and 100% (IQR 100%–100%) in control; in the mTICI 2b intervention subgroup it was 47% (IQR 39%–58%).
  • Per-protocol and sensitivity analyses were directionally consistent with the primary analysis.

Adverse Events / Safety:

  • Any hemorrhagic transformation at 24 hours: 48/215 (22.3%) versus 71/225 (31.6%); OR 0.62 (95% CI 0.41–0.95).
  • Symptomatic intracranial hemorrhage: 3.5% versus 3.9%, with no significant difference.
  • 90-day mortality: 15.4% versus 15.6%, with no significant difference.
  • Serious adverse events: 34/215 (15.8%) versus 27/225 (12.0%).
  • No serious adverse events attributable to vasopressor use were identified, but only a small proportion of patients received vasopressors.

Figures

Flow diagram of HOPE trial allocation, follow-up, and analysis
Figure 1. Flow diagram of allocation, follow-up, and analysis of trial participants. ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; BP, blood pressure; mRS, modified Rankin Scale; mTICI, modified Treatment in Cerebral Infarction.

Source: PMC PMC13247842 — jamaneurol-e261706-g001.jpg. Click image to expand.

Mean systolic blood pressure patterns by reperfusion status
Figure 2. Line graphs showing patterns of systolic blood pressure. Mean systolic BP is shown for patients with incomplete reperfusion (mTICI 2b) and patients with near-complete or complete reperfusion (mTICI 2c or 3). Error bars indicate SD.

Source: PMC PMC13247842 — jamaneurol-e261706-g002.jpg. Click image to expand.

Primary 90-day functional outcome by treatment group
Figure 3. Bar graph showing primary functional outcome measured by mRS score at 90 days.

Source: PMC PMC13247842 — jamaneurol-e261706-g003.jpg. Click image to expand.

Criticisms

  • The trial stopped early because ongoing funding was unavailable and did not reach its planned sample size; the resulting estimate may be imprecise and the apparent effect may be exaggerated by early stopping.
  • The population was highly selected: anterior circulation only, ASPECTS ≥6, successful reperfusion, no major unrevascularized stenosis, and mostly mTICI 2c/3 (90.2%). Results should not be generalized to posterior circulation stroke, persistent large-artery stenosis, poor early imaging, or incomplete reperfusion without further evidence.
  • Only 43 patients had mTICI 2b reperfusion, and the subgroup did not show a clear benefit. The trial therefore does not establish that the 140–160 mm Hg target is beneficial for incomplete reperfusion.
  • Baseline hypertension was more common in the control group, and the control group had numerical imbalances including somewhat more terminal ICA occlusion and slightly higher NIHSS; residual chance imbalance could contribute to the result.
  • The intervention combined different target thresholds, more frequent monitoring, protocolized rescue for hypotension, and permitted vasopressors. The trial cannot identify which component produced the observed benefit.
  • Treatment was open-label, several antihypertensive agents were permitted, and serious adverse events numerically favored control (12.0% vs 15.8%), despite no significant difference.

Funding

The article lists support from Instituto de Salud Carlos III (ISC III), the Ministerio de Ciencia e Innovación, FEDER, and RICORS-ICTUS. The full text does not state a specific role for the funders in the design, conduct, analysis, or reporting. Trial registration: ClinicalTrials.gov NCT04892511.

The paper

  • Authors. Camps-Renom et al.
  • Title. Personalized Blood Pressure Targeting After Endovascular Therapy for Acute Ischemic Stroke: A Randomized Clinical Trial.
  • Journal. JAMA Neurology.
  • Year. 2026.
  • DOI. 10.1001/jamaneurol.2026.1706
  • PMCID. PMC13247842
Deep Dive — click to expand

What this is

HOPE asks whether post-thrombectomy BP should be treated as a single ceiling or as a physiologic prescription that depends on how much reperfusion was achieved. In 440 analyzed patients with anterior-circulation occlusion and successful reperfusion, the tailored protocol increased 90-day independence by 13.3 percentage points and reduced any hemorrhagic transformation. The important signal is not simply “lower BP is better”: the protocol lowered BP to 100–140 mm Hg after mTICI 2c/3 but deliberately maintained 140–160 mm Hg after mTICI 2b, while using close monitoring and rescue for hypotension.

1. Shadow Audit

The headline result makes the strategy look like a clean test of individualized targets, but the randomized contrast was broader than the target numbers. The intervention group had substantially more frequent BP measurement, a 72-hour protocol, explicit lower-safety thresholds, and access to saline or vasopressors; the control group followed a permissive ceiling of ≤180 mm Hg with much less frequent monitoring after the first day. In the dominant mTICI 2c/3 group, the average BP difference was only 9 mm Hg, yet the intervention produced a 13.3-point absolute functional difference. That makes a BP target biologically plausible, but it also leaves protocol intensity, detection of deterioration, and early postprocedural care as alternative explanations. The paper itself notes that the mTICI 2b subgroup—where the distinctive higher target should matter most—was tiny and showed no clear benefit.

2. Inversion Engine

For the paper’s practical conclusion to invert, a larger trial would need to show that the observed 13.3-point benefit is mostly a chance imbalance or an early-stopping exaggeration, with the true risk difference near zero or negative. The 95% CI still permits a modest benefit as small as 4.1 points, but it does not prove a clinically large effect; the approximate NNT from the point estimate is 8, with a wide plausible range of roughly 4–24. The mechanistic inversion is also straightforward: if reducing pressure after complete reperfusion lowers perfusion below the patient’s autoregulatory requirement, infarct expansion or neurological deterioration should erase the hemorrhage reduction. Conversely, if the benefit comes from monitoring and rescue rather than the target itself, a trial that equalizes monitoring intensity while retaining different targets could shrink the effect toward zero.

3. Second-Order Catalyst

If reproduced, the first practice change would be in the neurointerventional-to-stroke-unit handoff: the final mTICI grade would become a required input to the immediate postprocedural BP order rather than a retrospective angiographic detail. A protocol could start with 100–140 mm Hg after mTICI 2c/3 and 140–160 mm Hg after mTICI 2b, define a lower safety floor, specify monitoring frequency, and give nursing staff an escalation pathway for fluids or vasopressors. The first patients likely to move are those with excellent reperfusion and a high hemorrhagic-transformation risk, but the change should be labeled provisional until a larger trial confirms both safety and benefit.

4. Asymmetric Leverage

The leverage is potentially large because a modest shift in functional independence applies to every successful thrombectomy, not only to rare complications. In HOPE, preventing roughly one additional dependent outcome for every eight treated patients is a large systems-level payoff if the estimate is real. The asymmetry cuts both ways: the evidence base is only 440 analyzed patients, while the intervention would affect thousands of thrombectomy admissions. A small overestimate therefore creates a large implementation cost through nursing workload, antihypertensive exposure, hypotension, and possible vasopressor use. The safe leverage point is not immediate universal adoption; it is standardizing reperfusion-aware orders and collecting prospective outcomes while the question is resolved.

5. Paradigm Destroyer

The paper challenges the reflex that every successfully reperfused patient should receive either permissive hypertension or the same intensive BP ceiling. It also undermines the opposite reflex—equating an attractive randomized result with permission to rewrite protocol immediately—because HOPE was underpowered for the 2b subgroup, stopped early, and excluded many patients at risk of hemodynamic failure. A two-sentence protocol update for tomorrow morning would be: “Document final mTICI grade in the post-thrombectomy handoff and do not use a single BP target for all reperfused patients. Consider a reperfusion-stratified target only within a monitored protocol or trial, with an explicit lower safety limit and rescue plan.”

MVP — Minimum Viable Proof

The minimum practice-changing proof is replication in a larger, adequately powered randomized trial showing that, among anterior-circulation thrombectomy patients with mTICI 2c/3, a 100–140 mm Hg strategy improves 90-day mRS without increasing symptomatic intracranial hemorrhage, mortality, or neurological deterioration, while a separate adequately sized mTICI 2b cohort confirms that 140–160 mm Hg does not cause harm. Equalizing monitoring intensity between arms would also be essential to isolate the BP target.

Best Combination

Combine HOPE with the prior neutral or harmful intensive-lowering trials as evidence against one-size-fits-all BP treatment, not as proof that lower is universally better. The most coherent synthesis is: after complete or near-complete reperfusion, moderate control may be beneficial in a selected population with relatively preserved hemodynamic reserve; after incomplete reperfusion or significant stenosis, excessive lowering may threaten collateral flow. HOPE’s value is therefore methodological—reperfusion status, autoregulatory reserve, monitoring, and rescue should be incorporated into the next trial—rather than a definitive universal target.

Overvalue Warning

First, do not treat the 13.3-point absolute difference as a guaranteed NNT of 8: the trial stopped early, was small, and allowed several co-interventions that traveled with the BP target. Second, do not generalize the 100–140 mm Hg target to patients with mTICI 2b, posterior-circulation stroke, persistent stenosis, poor ASPECTS, or populations with different vascular-risk profiles; the trial included only 43 mTICI 2b patients and excluded major unrevascularized stenosis.

Educational use notice. The Time Is Brain Review is dedicated to medical education. Figures from published articles are embedded for teaching purposes, with attribution to the original publication. We do not claim copyright over any embedded figure; all rights remain with the original publisher and authors under the article's published license. If you are a rights holder and would like a figure removed, please contact the editorial team. See our editorial notice for the full policy.