A large randomized trial investigating intensive blood pressure lowering in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.
“Intensive control of systolic blood pressure below 120 mm Hg should be avoided to avoid compromising functional recovery in patients who have received endovascular thrombectomy for acute ischemic stroke due to large-vessel occlusion intracranial,” the researchers conclude.
The results of the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology at the University of New South Wales, Sydney, Australia, on October 28 at the 14th World Stroke Congress (WSC), which takes place in Singapore. .
The study was simultaneously published online in The Lancet.
“What our results have shown quite convincingly is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure to 120 mm Hg systolic for 3 days is too low for too long . We shouldn’t go that far,” Anderson told theheart.org | Cardiology Medscape.
Anderson said the trial has provided an important message for clinical practice.
“This result is not what we expected, but it is a definitive result and gives us a lower margin of safety for blood pressure in patients with acute ischemic stroke. That, in itself, is a big step forward.”
He noted that the optimal blood pressure for these patients is not known.
“We need to do more testing to determine the optimal blood pressure in these acute patients, but maybe we should be aiming more toward 140 mm Hg,” he suggested.
“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to prevent levels from falling too low. We need to make sure that we do not exceed 120 mm. Hg or below.”
The chair of the CSM session where the trial was presented, Jeyaraj Pandian, MD, chief of neurology at Christian Medical College, Ludhiana, India, who is the current vice president of the World Stroke Organization, say: “This is a very important result. It has important practical implications.”
By way of background, Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the more likely they will have a worse outcome.
“In theory, if we can control blood pressure, we can improve outcomes,” he said.
In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount, around 140 mm Hg, which is lower than currently recommended in guidelines, was associated with a reduction in bleeding complications from thrombolysis and it looked safe, but he did it. it doesn’t improve recovery, Anderson noted.
“This trial was done before mechanical thrombectomy was routinely adopted, and this procedure has become the standard of care for large-vessel occlusive strokes, but we don’t know what to do with blood pressure in these patients,” he added.
A smaller French trial suggested that lowering blood pressure to 130 mm Hg, rather than a more liberal 130–180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional result.
“In stroke patients with large-vessel occlusion, blood pressure often rises to very high levels. There is a wide range of opinions about what to do about it: whether to lower it and to what extent,” Anderson said. “We ran the current ENCHANTED2/MT test to analyze this problem.”
The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated into two groups. In one group, blood pressure was aggressively reduced to <120 mm Hg within 1 hour of reperfusion, and blood pressure remained at this level for 3 days. In the other group, a more liberal approach was used: blood pressure was kept between 140 and 180 mm Hg.
The primary endpoint was disability, as measured by the modified Rankin Scale (mRS) score at 90 days.
The study was initiated in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2000 patients.
However, in March this year, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment to the trial be suspended due to a safety signal. All patients who had been recruited were from China.
These patients were followed for 3 months, after which the DSMB recommended that the trial be stopped because safety was still an issue.
The mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the group with more intensive treatment; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
Worse disability scores
The results showed that patients who underwent more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on an analysis of change in mRS than those in the less intensive group (odds ratio common). [OR], 1.37; 95% CI, 1.07 – 1.76).
The unfavorable change in mRS scores in the more intensive group was consistent in the adjusted sensitivity analysis and there was no significant heterogeneity in the treatment effect on the primary outcome in all prespecified subgroups.
The incidence of death or neurological impairment at 7 days was higher in the more intensive treatment group than in the less intensive treatment group (pooled OR, 1.53), and a difference emerged between the groups at 24 hours.
The incidence of death or disability (mRS score, 3–6) at 90 days was higher among patients in the more intensive treatment group than in the less intensive treatment group (53% vs 39%; OR, 1.85; P = 0.0001). ).
Among those who survived, more patients in the more intensive treatment group had major disability (mRS score, 3–5) at 90 days than patients in the less intensive treatment group (43% vs 28%; OR, 2, 07; P). = 0.0001).
No difference in episodes of ICH or severe hypotension
The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not differ significantly between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.
“Our results show that intensive blood pressure lowering appears to be associated with worsening physical disability. Although there was no difference in mortality rates between the two groups, lower blood pressure appeared to compromise ability to recover from stroke,” Anderson said. .
As for the possible mechanism of damage, he suggested that the intensive lowering of blood pressure might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
What levels should they target?
Anderson emphasized that it was important to have conducted this trial.
“Current guidelines recommend a very conservative level of blood pressure in patients with acute ischemic stroke, below 180 mm Hg. But no lower limit is recommended.
“Most doctors aim for the 140 mm Hg mark, but there is a wide variation of opinion about what to do,” he said. “Some doctors treat aggressively, believing that lower pressures might be beneficial in preventing bleeding and swelling, and others prefer to keep the levels higher. Our results have helped provide some guidance to respect”.
When asked what an optimal goal would be, Anderson replied, “For now, I think a goal of about 140 mm Hg systolic would be reasonable, and there’s no evidence to go below that.”
Yvo Roos, MD, professor of acute neurology at the University Medical Center, Amsterdam, Netherlands, co-author of the ENCHANTED2/MT trial, also commented for theheart.org | Cardiology Medscape.
“The real significance of the results of this study is that they show that lowering the blood pressure too much is detrimental to the outcome. My personal interpretation, looking at the results of this study but also the previous studies, is that we should aim to a goal of 140–150 mm Hg. This is true for patients on recanalization therapy. For patients without any therapy, I would be even more careful about lowering blood pressure and recommend staying below 180 mm Hg.” .
As for whether these results are generalizable to other populations, given that the patients were Chinese, Anderson noted that Asians have higher rates of intracranial atherosclerosis and more heart and kidney blood pressure complications than white patients. Patterns of stroke management also differ.
“These points raise questions about generalizability, and while I think this is an issue to consider, I don’t think it should detract from the clarity of these results,” he commented.
The study is supported by grants from Shanghai Hospital Development Center, National Health and Medical Research Council of Australia, China Stroke Prevention Project, Changhai Hospital of Shanghai, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech and Penumbra. . Anderson has received grants from the National Health and Medical Research Council and the Medical Research Futures Fund of Australia, the UK Medical Research Council,…