BP-TARGET: Intensive BP Lowering No Benefit Over Standard Care for Hemorrhage Reduction

A low blood pressure target to reduce intraparenchymal hemorrhage rates after successful reperfusion therapy for large vessel occlusion stroke showed no benefit over standard care, the randomized BP-TARGET trial found.

“An intensive systolic blood pressure target of 100–129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal hemorrhage rates at 24–36 hours as compared with a standard care systolic blood pressure target of 130–185 mm Hg,” wrote Mikael Mazighi, MD, of Rothschild Foundation Hospital in Paris, and co-authors in Lancet Neurology.

“Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure,” they added. “Further studies are needed to understand the association between blood pressure and outcomes after reperfusion.”

Wendy Ziai, MD, and Mais Al-Kawaz, MD, both of Johns Hopkins University in Baltimore, agree that more study is needed and in an accompanying editorial, observed that “BP-TARGET was limited by a lack of adherence to the blood pressure target and substantial unintended crossover, with each group spending approximately a third of the 24-hour study duration in the systolic blood pressure target range of the other group.”

“The average systolic blood pressure, however, suggests a U-shaped association with the primary outcome, with the lowest hemorrhage rates at 110–140 mm Hg compared with the extremes, similar to reported observational data,” Ziai and Al-Kawaz noted.

“BP-TARGET should be considered as a pilot study,” they added. “Powering the trial on a difference of 15% in rates of intraparenchymal hemorrhage was likely to be an overestimate; observational data suggest smaller differences in hemorrhage rates when comparing similar systolic blood pressure intervals. Future trials will require consideration of small effect sizes as the norm.”

High systolic blood pressure in the 24 hours following successful endovascular therapy has been associated with intracranial hemorrhage, mortality, and hemicraniectomy. A 2020 study found that systolic blood pressure reduction was associated with lower odds of poor outcome only in those with complete reperfusion.

Mazighi and colleagues conducted an open-label randomized trial of adults 18 years or older with acute anterior circulation large-vessel occlusion ischemic stroke. All participants were successfully treated with endovascular therapy to achieve reperfusion with no periprocedural hemorrhagic complication. Reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) score of 2b or 3 (restoration of more than half or all of downstream circulation, respectively).

The study was powered to detect a 15% difference in intraparenchymal hemorrhage rates and the primary analysis was intention-to-treat. Participants were patients from four French academic medical centers seen between June 2017 and September 2019. Median age was 76-77, and 51% of the intensive and 45% of the standard target groups were men. Intravenous thrombolysis was used in 54% and 52% of the intensive and standard target groups, respectively.

Patients were randomized in the first post-procedural hour to the intensive (n=158) or the standard systolic blood pressure target (n=160). Mean systolic blood pressure during the 24 hours following reperfusion was 128 mm Hg in the intensive group and 138 mm Hg in the standard group.

Patients had blood pressure measurements every 15 minutes for two hours, then every 30 minutes for six hours, and hourly thereafter. Brain CT 24-36 hours after the procedure was the basis for the primary outcome. At 24 hours, the rate of receiving at least one antihypertensive drug was 83% in the intensive and 20% in the standard target group.

The intensive target group spent a median 61% of the time in their target range; participants in the standard target group spent 66.6%. Each group spent about 30% of the time in the target range of the other group.

For the primary outcome, the rate of radiographic intraparenchymal hemorrhage at 24–36 hours on CT did not differ for the intensive and standard target groups, at 42% and 43%, respectively (adjusted OR 0.96, 95% CI 0.60-1.51; P=0.84).

Hypotension — the primary safety outcome — did not significantly differ between groups either, at 8% and 3% in the intensive and standard target groups, respectively. Death in the first week occurred in 7% of the intensive and 4% of the standard target groups.

One explanation for the findings may be that “the systolic blood pressure difference of 10 mm Hg we observed between groups was modest,” Mazighi and co-authors said. In addition, “the optimal systolic blood pressure value to reach after reperfusion might be debatable,” they added.

The findings also highlight the difficulty of controlling systolic blood pressure “despite best-practice management in dedicated stroke units,” they pointed out.

1. A low blood pressure target to reduce intraparenchymal hemorrhage rates after successful reperfusion therapy for large vessel occlusion stroke showed no benefit over standard care, the randomized BP-TARGET trial found.

2. Mean systolic blood pressure during the 24 hours following reperfusion was 128 mm Hg in the intensive group and 138 mm Hg in the standard group, but the study was limited by substantial unintended crossover from one group to another.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Cat ID: 914

Topic ID: 74,914,730,914,130,192,925