Lower BP Targets After Stroke Thrombectomy Don’t Seem to Help: BEST-II

It’s unlikely that aiming for lower than recommended blood pressure goals will benefit patients who undergo successful endovascular therapy (EVT) for an acute ischemic stroke, according to the results of the BEST-II trial.

Based on the design, researchers couldn’t conclude that treating to lower BP goals would be futile in terms of shrinking infarcts and improving patient function. “However, it is important to keep in mind that, by design, we cannot rule out the potential for harm of lower blood pressure targets,” Eva Mistry, MBBS (University of Cincinnati, OH), reported today at the International Stroke Conference in Dallas, TX.

“In fact,” she said, “the point estimate of treatment effect on utility-weighted mRS [modified Rankin Scale] was in the direction of harm.”

Taking all of that into account, along with the findings of prior studies like ENCHANTED2/MT and BP-TARGET, “the investigators believe that continuing a pivotal inquiry of lower post-EVT blood pressure targets may not be the best use of research resources,” Mistry concluded. She noted, though, that there are some ongoing trials that will provide additional insights.

So for now, she told TCTMD, “my takeaway and my personal practice going forward would be to just [go] back to practicing permissive hypertension. In other words, I wouldn’t artificially lower the blood pressure of these patients below a certain level unless it is above 180 mm Hg.”

Exploring Lower Goals

That advice fits with current guidelines, which recommend maintaining BP at less than 180/105 mm Hg after endovascular stroke therapy. However, practice is widely variable in the community, with a recent national survey showing that centers use systolic targets ranging from as low as < 120 mm Hg up to the guideline-recommended < 180 mm Hg.

There is observational evidence that suggests higher BP levels after stroke thrombectomy are associated with worse patient outcomes, although BP-TARGET failed to show a benefit of lower targets in terms of hemorrhagic outcomes and ENCHANTED2/MT showed harm from very low targets.

The BEST-I prospective cohort study identified a peak systolic BP of 158 mm Hg after EVT as the best cutoff to dichotomize good versus bad outcomes, and retrospective cohort studies indicated that outcomes were improved at moderate BP levels between 140 and 160 mm Hg.

To further explore this issue, Mistry and colleagues designed BEST-II, a phase II trial meant to address safety and preliminary efficacy. The researchers enrolled 120 patients (mean age 69.6 years; 57.5% women) who underwent successful EVT for a large-vessel occlusion in the anterior circulation of the brain at three study centers. They were randomized to three BP targets in the 24 hours immediately after the procedure: < 140 mm Hg, < 160 mm Hg, and ≤ 180 mm Hg. Nicardipine was used as the first-line BP-lowering agent.

There were two primary endpoints, both assessed from the perspective of futility: infarct volume on 36-hour brain imaging and 90-day utility-weighted mRS score.

There was a hint of benefit in terms of a smaller mean infarct volume at lower BP targets and a hint of harm in terms of mRS score, although statistically the researchers couldn’t conclude that aiming for lower BPs was futile for either endpoint. In addition, there was no unequivocal evidence of harm.

The rate of any intracerebral hemorrhage (ICH) was 31.7% overall, with a 4.2% rate of symptomatic ICH. Rates were relatively similar across the three study arms.

To further assess the futility of the two lower BP targets evaluated in the study, the investigators predicted the probability of success of future trials of varying sizes. The probability of success ranged from a low of 16% for a 400-patient study to a high of 28% for a 2,400-patient study.

An Important Question

Commenting on the findings for TCTMD via email, Thanh Nguyen, MD (Boston University, MA), said BEST-II is an interesting study exploring an important question.

She noted that the average BPs achieved in the patients aiming for < 160 mm Hg and ≤ 180 mm Hg were similar, and said it would be interesting to understand why that happened. “Is it because patients autoregulate to where they need to be, or is it because of target beyond planned range with nicardipine?” she said. “If it's the former, it shows the body will do what it needs to do in response to a reperfused artery and it may be best to let nature take its course.”

Overall, Nguyen said the findings of BEST-II validated what was seen in the ENCHANTED2/MT trial, “that perhaps we should avoid a target < 120 mm Hg as a common overlapping range” between the two trials.

She agreed with the BEST-II investigators that individualized BP control may be the way to go after successful EVT, which leads to additional important questions: “Who are the patients in whom we should lower the blood pressure? Who are the patients who autoregulate their blood pressure on their own? Are patients who maintain higher blood pressure after thrombectomy indicative of a higher-risk population in need of close observation?”

The implication, Nguyen said, “is that we may need to be cautious about intensive lowering of blood pressure in patients who had successful clot removal, as had also been observed in another trial in China.”

The patient’s neurological exam should guide decisions about BP management after a stroke, Nguyen said. “If they have a good exam with a low blood pressure, this is a satisfactory goal (ie, we would not need to artificially raise their blood pressure),” she said. “In patients who have higher blood pressure after successful clot removal, one can let the patient autoregulate. The question is what is the acceptable upper limit for these patients, above which one would intentionally lower their blood pressure.”