Extreme BP-Lowering Harmful After Stroke Thrombectomy: ENCHANTED2/MT

Overly tight control of blood pressure after successful endovascular thrombectomy for acute ischemic stroke may not be a good idea, the randomized ENCHANTED2/MT trial indicates.

Aiming for a systolic BP target below 120 mm Hg in the days following the procedure increased the likelihood of poor functional outcomes at 90 days compared with a more-conservative target between 140 and 180 mm Hg (common OR 1.37; 95% CI 1.07-1.76), Craig Anderson, MBBS, PhD (The George Institute for Global Health, University of New South Wales, Sydney, Australia), reported at the World Stroke Congress in Singapore last week.

Intensive treatment also worsened the composite outcome of death or early neurological deterioration, and of major disability at 90 days, with no differences in symptomatic intracerebral hemorrhage, serious adverse events, or death alone.

Therefore, lowering systolic BP to less than 120 mm Hg after successful clot retrieval “should be avoided in clinical practice,” Anderson and his colleagues write in a paper published simultaneously in the Lancet, adding that further trials are warranted to identify the optimal target.

Eva Mistry, MD (University of Cincinnati, OH), who wrote an accompanying comment with Thanh Nguyen, MD (Boston University, MA), agreed, telling TCTMD that “generally speaking, avoiding extreme blood pressure-lowering, even after successful mechanical thrombectomy, should be the way to go.”

Mistry is the principal investigator of the ongoing BEST-II trial, which randomized patients to three different systolic BP targets after thrombectomy: ≤ 180, < 160, and < 140 mm Hg. She said she hopes to present the findings, which should provide more insights into optimal BP management after the procedure, at the International Stroke Conference in February. In the meantime, Mistry said, BP targets should be individualized based on a patient’s concomitant conditions, vascular anatomy, and procedural complications.

The ENCHANTED2/MT Trial

Via email, Anderson explained that epidemiological studies have shown a relationship between increasing BP levels and poor outcomes among patients with acute ischemic strokes caused by large-vessel occlusions. Though mechanical thrombectomy has been established as a safe and effective way to improve outcomes in this setting, many patients—particularly those with high BP after the procedure—still have impaired outcomes. “Thus, the simple approach of controlling BP after endovascular treatment could improve outcome,” Anderson said.

Guidelines conservatively recommend keeping systolic BP below 180 mm Hg after thrombectomy, but observational data suggest lower targets might be better. There are, however, limited randomized data that can be used to guide selection of a BP target after successful thrombectomy. One trial, BP-TARGET, showed that aiming for a systolic BP below 130 mm Hg did not improve outcomes over a higher goal, but it was too small to provide a definitive answer, Anderson said.

On that background, there is much variation in BP management after thrombectomy across centers. “That is why an RCT is required to standardize or guide clinical practice and policy,” he added.

The caution that this trial provides in terms of the harms of extreme blood pressure-lowering probably stands true. Eva Mistry

Despite being stopped early due to safety and efficacy concerns, ENCHANTED2/MT is the largest trial yet completed in this space. Across 44 hospitals in China, investigators enrolled 821 patients (mean age 68; 38% women) with acute ischemic stroke who had elevated BP after successful endovascular thrombectomy and randomized them to intensive BP-lowering to a systolic goal below 120 mm Hg or to less-intensive treatment to a goal of 140 to 180 mm Hg.

Mean systolic BP at baseline was about 158 mm Hg. Mean readings at 1 hour and 24 hours were 125 and 121 mm Hg, respectively in the intensive arm and 143 and 139 mm Hg, respectively, in the control arm.

But rather than improving outcomes, aiming for the lower goal worsened functional recovery according to the distribution of scores on the modified Rankin Scale at 90 days (primary efficacy outcome), and also increased the odds of death or early neurological deterioration (common OR 1.53; 95% CI 1.18-1.97) and major disability at 90 days (OR 2.07; 95% CI 1.47-2.93).

Intensive BP control likely “compromised blood flow through the small blood vessels in the brain with ischemic injury from the previously blocked large vessel,” Anderson suggested, noting that in the microcirculation, “there are a variety of pathophysiological inflammatory and healing processes that are likely compromised by changes in blood flow.”

The trial included only those patients with a good thrombectomy result, “but presumably some of these patients still had incomplete opening up of the clot from endovascular treatment, although we could not find any clear patient or procedural characteristic where the results were worse (or better),” Anderson continued. “We are still undertaking analyses of the brain scans and other radiological investigations from our patient participants to better understand the relations between the study treatment and cerebral blood flow.”

How Definitive Are the Findings?

Mistry said she was only “moderately surprised” by the findings of the trial due to the mix of previous observational data, with some studies indicating a U-shaped relationship between BP and patient outcomes—with both high and low values associated with worse functional outcomes—and others indicating that systolic BP values as low as 120 mm Hg could be associated with favorable results.

There is some question about how generalizable the findings of ENCHANTED2/MT are outside of the Chinese patient population enrolled, she indicated, pointing to two issues in particular. First, Asian patients are more likely to have strokes with an underlying atherosclerotic etiology than are patients in Western countries, who are more likely to have cardioembolic events. And second, BP-lowering was achieved using urapidil in roughly three-quarters of patients in this trial, whereas in other countries like the United States, calcium channel blockers and beta-blockers are more commonly used.

But even though the patients enrolled in ENCHANTED2/MT may not be generalizable to all patients treated around the world, the findings regarding the lower treatment goal are likely applicable more broadly, Mistry said. “The caution that this trial provides in terms of the harms of extreme blood pressure-lowering probably stands true.”

Anderson pointed out that the trial has not identified an optimal level of BP control after stroke thrombectomy. “While one may infer that it is likely to be < 140 mm Hg, which is beyond current guideline recommendations of < 180 mm Hg, the foundation of modern healthcare and practice recommendations should be based on high-quality, level-one RCT evidence,” he said. “That is why there is still room for further RCTs in this topic, and these will realize results over the next few years.”

In addition to BEST-II, several other ongoing trials are evaluating BP targets after thrombectomy, including ENCHANTED2, OPTIMAL-BP, CRISIS I, and HOPE.