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

Clinical Question (PICO)

In adults with anterior-circulation large-vessel occlusion stroke who achieve successful reperfusion (mTICI ≥2b) after endovascular therapy and were functionally independent before stroke, does a 72-hour reperfusion-guided systolic blood pressure (SBP) strategy improve 90-day functional independence compared with guideline-recommended SBP management (≤180 mm Hg)? The protocol prespecified different targets according to reperfusion: 140–160 mm Hg for mTICI 2b and 100–140 mm Hg for mTICI 2c/3. Prespecified subgroup analyses assessed whether the treatment effect varied across eight clinical and treatment subgroups; collateral status was to be reported separately.

Bottom Line

In the HOPE trial, a reperfusion-guided SBP strategy increased 90-day functional independence from 47.1% to 60.0% (reported absolute risk difference, 13.3%; 95% CI, 4.1%–22.6%; P = .005; OR, 1.71; 95% CI, 1.17–2.50). Hemorrhagic transformation was also less frequent, while symptomatic intracranial hemorrhage and mortality were similar. The result supports a tailored, rather than one-size-fits-all, approach—but the trial stopped early, enrolled predominantly patients with mTICI 2c/3 reperfusion, and the authors describe the findings as hypothesis-generating rather than practice-changing.

Design

Trial type: Investigator-initiated, multicenter, prospective, phase 3 randomized clinical trial; open-label treatment with blinded end-point assessment (PROBE design)
N: 440 in the intention-to-treat analysis (446 randomized; 215 intervention, 225 control)
- Reperfusion-guided SBP strategy: 215
- Guideline-recommended management: 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 (assessment window ±15 days)
Analysis: Intention-to-treat unadjusted logistic regression for the primary outcome; prespecified adjusted sensitivity analysis, ordinal mRS shift analysis, per-protocol analyses, and multiple-imputation sensitivity analysis
Primary outcome: Favorable functional outcome, defined as modified Rankin Scale (mRS) score 0–2 at 90 days

Population

Inclusion Criteria

Age 18 years or older
Prestroke functional independence (mRS score 0–2)
Acute ischemic stroke from anterior-circulation large-vessel occlusion, including terminal internal carotid, proximal M1 or M2, proximal A1, or tandem occlusion
Endovascular therapy completed within 24 hours of symptom onset
Successful reperfusion after endovascular therapy, defined as mTICI score ≥2b
Hypertension or an admission SBP above 140 mm Hg was not required

Exclusion Criteria

Alberta Stroke Program Early CT Score (ASPECTS) <6
Posterior-circulation stroke
Congestive heart failure or arterial dissection
Nonrevascularized intracranial or extracranial stenosis of 50% or more 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 (12) years; 233 participants (53.0%) were women
Median baseline NIHSS, 16 (IQR, 10–20); median ASPECTS, 9 (IQR, 8–10)
Median prestroke mRS, 0 (IQR, 0–1)
Cardioembolic stroke was the presumed cause in 251 participants (60.6%); large-artery atherosclerosis accounted for 44 (10.6%)
Final reperfusion was mTICI 2b in only 43 participants (9.8%) and mTICI 2c/3 in 397 (90.2%)

Interventions

Reperfusion-guided hemodynamic strategy: For 72 hours, SBP 140–160 mm Hg after mTICI 2b and 100–140 mm Hg after mTICI 2c/3. Intravenous labetalol or urapidil were first-line antihypertensives, with other agents permitted. Isotonic saline, followed by phenylephrine, ephedrine, or norepinephrine when necessary, was recommended for hypotension or target-range augmentation.
Guideline-recommended management: Standard care with SBP ≤180 mm Hg for 72 hours.
BP was monitored at least every 30 minutes during the first 24 hours and hourly from 24–72 hours in the intervention group, compared with hourly and then every 6 hours in the control group. Treatment was interrupted for predefined safety events or hemodynamic instability.

Outcomes

Primary Outcome (mRS score 0–2 at 90 days):

Intervention: 129/215 (60.0%); control: 106/225 (47.1%)
Reported absolute risk difference: 13.3% (95% CI, 4.1%–22.6%; P = .005)
Unadjusted OR: 1.71 (95% CI, 1.17–2.50)
Adjusted sensitivity analysis: OR, 1.71 (95% CI, 1.11–2.63; P = .02)
Multiple-imputation sensitivity analysis: OR, 1.67 (95% CI, 1.14–2.45; P = .008)
Ordinal shift toward better mRS scores: common OR, 1.43 (95% CI, 1.03–2.00)
The eight prespecified subgroup analyses found no significant heterogeneity of treatment effect. No clear benefit was demonstrated in the small mTICI 2b subgroup; the detailed subgroup estimates are reported in the supplement rather than the main article.

Secondary Outcomes:

Hemorrhagic transformation at 24 hours: 22.3% (48/215) with intervention vs 31.6% (71/225) with control; OR, 0.62 (95% CI, 0.41–0.95; P = .03)
The full 90-day mRS distribution favored the intervention; mRS 0 occurred in 24.2% vs 17.8% (OR, 1.43; 95% CI, 1.03–2.00; P = .03)
Early neurological deterioration was not significantly different at 24 hours (OR, 0.67; 95% CI, 0.35–1.30; P = .24) or 72 hours (OR, 1.10; 95% CI, 0.50–2.30; P = .81)

Adverse Events / Safety:

Symptomatic intracranial hemorrhage: 3.5% vs 3.9%; OR, 0.89 (95% CI, 0.31–2.52; P = .82)
Any PH2 hemorrhage: 3.4% vs 4.1%; OR, 0.81 (95% CI, 0.28–2.21; P = .68)
Ninety-day mortality: 15.4% vs 15.6%
Serious adverse events: 15.8% vs 12.0%; OR, 1.38 (95% CI, 0.80–2.37; P = .25)
No serious adverse events attributable to vasopressor use were identified.

Figures

Flow diagram of 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.

Patterns of systolic blood pressure by reperfusion status — *Figure 2.* Line Graphs Showing Patterns of Systolic Blood Pressure. Mean systolic BP is shown for patients with incomplete reperfusion (mTICI score 2b) and patients with near-complete or complete reperfusion (mTICI score 2c or 3). Error bars indicate SD.

Primary functional outcome by modified Rankin Scale score — *Figure 3.* Bar Graph Showing Primary Functional Outcome Measured by Modified Rankin Scale (mRS) Score at 90 Days.

Criticisms

HOPE stopped early because ongoing funding was unavailable. The achieved sample was 440 in the intention-to-treat analysis, substantially below the recalculated target of 786 participants, so the relatively large observed effect may be imprecise or a chance finding.
The population was highly selected: 90.2% had mTICI 2c/3 reperfusion, patients with significant unrevascularized stenosis were excluded, and the trial was conducted at 11 Spanish comprehensive stroke centers. The findings should not be generalized automatically to posterior circulation stroke, residual large-artery disease, or populations with different autoregulatory risk.
The intervention was not only a BP target. It included substantially more frequent BP monitoring, permitted vasopressor support, a defined lower safety threshold, and discretionary selection among antihypertensive agents. The independent contribution of each component cannot be separated.
The mTICI 2b subgroup contained only 43 participants and showed no clear benefit; the subgroup-specific estimate is therefore weak evidence for the higher 140–160 mm Hg target.
Hypertension was more common in the control group, and the control group had numerically more terminal internal carotid occlusions and slightly higher NIHSS scores. These imbalances were addressed in sensitivity analyses but cannot be eliminated in a prematurely stopped trial.

Funding

The HOPE trial was funded by the Instituto de Salud Carlos III (ISC III), the Ministerio de Ciencia e Innovación (ICI20/00137), and FEDER. The HOPE team was supported by RICORS-ICTUS, ISC III, and the Ministerio de Ciencia e Innovación (RD21/0006/0006 and RD24/0009/0010). The funders had no role in the design or conduct of the study; data collection, management, analysis, or interpretation; manuscript preparation or review; or the decision to submit. Registered at ClinicalTrials.gov: NCT04892511.

The paper

Authors. Camps-Renom et al. (HOPE Study Group).
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 the post-thrombectomy BP problem is really one number for every brain. Among 440 patients with successful anterior-circulation reperfusion, matching SBP targets to the angiographic result—100–140 mm Hg after mTICI 2c/3 and 140–160 mm Hg after mTICI 2b—was associated with a 13.3-percentage-point reported increase in functional independence at 90 days. The signal is clinically large, but it comes from a prematurely stopped, unusually selected cohort in which nine of ten patients had mTICI 2c/3 reperfusion.

1. Shadow Audit

The headline is “personalized BP targeting,” but the trial tested a bundle. The intervention arm had BP checks at least every 30 minutes for 24 hours and hourly thereafter, compared with hourly and then every 6 hours in control; it also supplied explicit rescue options for hypotension and permitted vasopressors. The trial therefore cannot tell us that the SBP interval alone produced the benefit.

The apparent personalization is also dominated by the well-reperfused group: 397 of 440 analyzed patients (90.2%) had mTICI 2c/3, while only 43 (9.8%) had mTICI 2b. The group for whom the higher pressure target was intended had no clear benefit. HOPE’s positive result is consequently better described as evidence for a monitored, reperfusion-aware postprocedural pathway in a selected mTICI 2c/3 population than as proof that every mTICI 2b patient benefits from 140–160 mm Hg.

2. Inversion Engine

For the conclusion to invert, a larger and independently conducted trial would need to move the treatment effect toward the null or harm: an absolute difference near 0% rather than HOPE’s reported 13.3%, with no reproducible improvement in the mRS distribution. The current estimate is not immune to that inversion—the 95% CI reaches down to a 4.1-percentage-point benefit, and the trial stopped before its recalculated 786-participant target.

The clean test is not simply “repeat a lower SBP number.” It is to randomize enough patients, preserve stratification by reperfusion, equalize monitoring intensity, prespecify management of hypotension, and include enough mTICI 2b and large-artery-disease patients to test effect modification. If that trial shows no functional benefit, the HOPE effect becomes a precision-and-selection artifact rather than a new standard.

3. Second-Order Catalyst

The first institutions likely to change are comprehensive stroke centers that already record final mTICI grade and can manage a 72-hour neurocritical-care protocol. The first patients to move are those with mTICI 2c/3 reperfusion and no major residual stenosis—the group that supplied almost all of HOPE’s signal—not patients with incomplete reperfusion or impaired hemodynamic reserve.

The defensible near-term change is an implementation study: record final reperfusion, choose a provisional target, measure time in range, track hypotension and hemorrhagic transformation, and compare outcomes against the local baseline. A universal order-set change to intensive lowering would outrun this trial and conflict with the authors’ own “hypothesis-generating” qualification.

4. Asymmetric Leverage

A 13.3-percentage-point absolute improvement implies roughly one additional functionally independent patient for every 8 treated, using the author-reported effect size. That is a large payoff from a bedside protocol applied to the large denominator of patients who undergo thrombectomy and achieve reperfusion; even a smaller effect could matter at system scale.

The asymmetry cuts the other way for mTICI 2b. Only 43 patients contributed to that subgroup, and the higher target was not associated with a clear benefit. A striking overall result can therefore coexist with almost no evidence for the very subgroup in which the physiology is most uncertain.

5. Paradigm Destroyer

The reflex this paper challenges is the assumption that “successful reperfusion” makes every post-thrombectomy brain hemodynamically equivalent. It argues that angiographic reperfusion grade should inform BP management, just as it informs the interpretation of residual tissue risk.

A two-sentence protocol update for a research-ready pathway would read: “After anterior-circulation EVT with mTICI 2c/3, use a closely monitored provisional SBP target of 100–140 mm Hg for 72 hours; after mTICI 2b, use 140–160 mm Hg while avoiding hypotension and documenting rescue therapy. Treat these targets as an auditable trial protocol, not as a replacement for current guideline-level evidence, until a sufficiently powered replication confirms benefit and safety.”

MVP — Minimum Viable Proof

The minimum clinically meaningful statement is: in a representative, adequately powered post-thrombectomy population, a reperfusion-stratified 72-hour BP pathway must reproduce a meaningful improvement in 90-day mRS 0–2—approximately the HOPE signal of 60.0% versus 47.1%—without increasing symptomatic intracranial hemorrhage, mortality, or serious adverse events. HOPE supplies the signal; it does not yet supply the proof of transportability.

Best Combination

Use HOPE as the stratification hypothesis layered onto the prior randomized evidence, not as a command to reverse it. BP-TARGET and BEST-II were neutral, while ENCHANTED2/MT and OPTIMAL-BP raised concern about indiscriminate intensive lowering; current guidance therefore remains a relevant comparator. The synthesis is coherent if the question changes from “Should BP be lowered aggressively after EVT?” to “Which reperfused brains can tolerate which target, under what monitoring and rescue conditions?”

Overvalue Warning

First, do not equate the reduction in any hemorrhagic transformation (22.3% vs 31.6%) with a reduction in symptomatic ICH: sICH was 3.5% vs 3.9% and was not significantly different. Second, do not treat the 13.3-point functional difference as the isolated effect of a BP number; early stopping, baseline imbalances, selective exclusion of stenosis, unequal monitoring, and the tiny mTICI 2b subgroup all limit causal and external interpretation.

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