Lower target BP after endovascular therapy shows lack of potential benefit, signal of harm
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Lower target systolic BP after successful endovascular therapy demonstrated a signal of harm and only a marginal probability of benefit toward infarct volume and disability, a speaker reported.
The results of the BEST-II trial were presented at the International Stroke Conference.
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“This audience is very familiar that current guideline-recommended goals for blood pressure management after endovascular therapy (EVT) are permissive hypertension levels specifically less than 180/105 mm Hg [and] are recommended by both American and European stroke organization guidelines. However, in real-world practice of blood pressure management, especially after a successful endovascular stroke treatment defined as modified thrombolysis in cerebral ischemia, mTICI 2b-3 varies widely,” Eva Mistry, MBBS, stroke neurologist and assistant professor in the department of neurology and rehabilitation medicine at the University of Cincinnati, said during a presentation. “Evidence gaps still remain whether moderate post-EVT blood pressure targets improve patient outcomes.”
The researchers designed the phase 2, prospective, randomized, open-label, masked endpoint BEST-II trial to evaluate the efficacy and safety of lower BP targets using nicardipine in the 24 hours following successful EVT. A total of 120 participants (mean age, 70 years; 58% women; 88% white) were randomly assigned to a target systolic BP of 180 mm Hg or less, less than 160 mm Hg or less than 140 mm Hg.
The primary endpoints included infarct volume on 36-hour MRI or CT scan or 90-day utility-weighted modified Rankin scale score adjusted for baseline score (median baseline modified Rankin scale score, 0). Secondary safety endpoints included any intracerebral hemorrhage and symptomatic intracerebral hemorrhage.
BEST-II featured a futility design, for which systolic BP targets of less than 160 mm Hg and 140 mm Hg would be considered futile for evaluating in future trials if there was evidence of harm on either primary outcome and the predictive probability of success in future trials was less than 25%.
Researchers observed a significant reduction among participants in the 180 mm Hg or lower BP group compared with the 140 mm Hg arm but only a moderate separation between 180 mm Hg and 160 mm Hg groups.
Mistry stated that the point estimate of the effect of lower target systolic BP after successful EVT trended slightly in the direction of benefit; however, the one-sided CI goes from as much infarct volume benefit as 0.8 cc for every 1 mm Hg reduction in systolic BP and includes regions of harm, meaning the study did not support finding of futility, as there was not unequivocal evidence of significant harm, according to the presentation (adjusted slope of final infarct volume size, 0.29; one-sided P = .98).
In addition, the effect of lower systolic BP targeting after EVT on modified Rankin scale score trended slightly toward a harmful effect (slop of final modified Rankin scale score, 0.0019; P one sided = .92). Similar to the effect on infarct volume, the analysis did not provide unequivocal evidence of significant harm and support a finding of futility.
The researchers observed no significant differences in the occurrence of the secondary safety outcomes between BP target groups and no heterogeneity in treatment effect by age, baseline Alberta Stroke Program Early CT score, collateral grade and reperfusion grade using interaction terms, according to the presentation.
Moreover, the predictive probability of success in future trials was determined to be 25% in trials of 1,500 participants or more.
“Despite the COVID-19 pandemic, there was good fidelity to intervention. However, only moderate separation between the 180 mm Hg group and the 160 mm Hg group was observed. We failed to demonstrate futility; however, it is important to keep in mind that by design we cannot rule out the potential for harm of lower blood pressure targets,” Mistry said. “In fact, the point estimate of treatment effect on utility weighted modified Rankin scale was in the direction of harm. The 25% predictive probability of success for a pivotal trial was right at the mark of our prespecified threshold. For these reasons, that the trends are in the direction of harm and only a marginal possibility of benefit, although BEST-II was not designed or statistically powered to show a benefit, the investigators believe that a continuing a pivotal inquiry of lower post-EVT blood pressure targets may not be the best use of research resources.”
Reference:
- Lowering blood pressure after clot removal may not be safe; should be individualized. newsroom.heart.org/news/lowering-blood-pressure-after-clot-removal-may-not-be-safe-should-be-individualized. Published Feb. 10, 2023. Accessed Feb. 10, 2023.
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Mistry EA, et al. LB18. Presented at: International Stroke Conference; Feb. 8-10, 2023; Dallas (hybrid meeting).
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