BARCELONA — Very intensive and rapid lowering of blood pressure does not lead to better outcomes and may have a safety issue in patients with intracerebral hemorrhage (ICH) and high systolic blood pressure at baseline, according to the results of the ATACH-II trial.
The trial results were presented at the European Stroke Organisation Conference (ESOC) 2016 by Adnan Qureshi, MD, University of Minnesota, Minneapolis.
The ATACH-II trial was scheduled to be published in The New England Journal of Medicine to coincide with the ESOC presentation, but the journal released a statement the day before the presentation saying the study was not now going to be published on May 10 as previously announced "as some of the material is being updated by the authors." The journal added that the new publication date is still to be determined.
Dr Qureshi said he hoped the paper would be published "within the next couple of weeks."
Differences to INTERACT2
At first glance, the results of ATACH-II look to be conflicting with those of a similar trial — INTERACT2 — which did suggest a benefit in blood pressure lowering in patients with ICH. But Dr Qureshi pointed out that some important differences between the two trials need to be taken into account.
"INTERACT2 achieved moderate blood pressure reduction while patients in the intensive arm of ATACH-II had greater and faster blood pressure reduction," he said. "From our results, I think we can say that this very intensive and rapid blood pressure lowering is probably not a good idea. But by putting INTERACT2 and ATACH-II together we could say that some blood pressure reduction — to around 140 mmHg — is good and should continue to be the standard of care, but we don't need to be very aggressive and try and get down to 120 mmHg or below."
In his talk, Dr Qureshi explained that blood pressure often rises after ICH, and increasing data over the last few years suggest that high blood pressure in patients in the acute stages of ICH leads to expansion of the hematoma in the brain and more neurologic deterioration and death.
"We wanted to investigate whether by lowering blood pressure we can reduce the hematoma expansion and reduce death/disability," he said.
He noted that the INTERACT2 trial, reported in 2013, suggested that lowering blood pressure was safe and there was some suggestion of efficacy, "but this was rather borderline."
He added: "In ATACH-II, we enrolled patients with higher systolic pressures than in INTERACT2 and lowered the blood pressure to a greater extent and more rapidly to see if we could produce a greater effect."
The ATACH-II trial enrolled patients within 4.5 hours of ICH onset, with a Glasgow Coma Scale score of over 5, a hematoma volume less than 60 cm3, and systolic blood pressure over 180 mmHg. They were randomly assigned to blood pressure reduction with intravenous nicardipine to achieve systolic pressures in the range of 140 to 179 mmHg (standard care) or 110 to 139 mmHg (intensive blood pressure lowering).
The researchers planned to enroll 1280 patients, but the trial was stopped prematurely for futility after 1000 patients had been enrolled (500 in each group).
Results showed that the average systolic pressure was lowered to "close to 110 mmHg in the intensive group vs close to 140 mmHg in the standard group for the duration of the next 24 hours post randomization," Dr Qureshi reported.
The primary endpoint was death or disability (modified Rankin scale score, 4 - 6) at 90 days. This occurred in 38.7% of the intensive group vs 37.7% of the standard group, a nonsignificant difference (adjusted relative risk, 1.04; 95% confidence interval, 0.85 - 1.27; P = .72).
Hematoma Expansion Reduced
But there did appear to be a positive effect on hematoma expansion with intensive blood pressure reduction, with 18.9% of the intensive group showing a greater than 33% increase in hematoma volume compared with 24.4% of the standard group (relative risk, 0.78; P = .08).
In terms of safety, treatment-related adverse effects in the first 72 hours occurred in 1.6% of the intensive group and 1.2% of the standard group, a nonsignificant difference. Severe hypotension was also infrequent and did not differ between the groups.
However, there was a borderline-significant increase in any serious adverse event in the 90-day course of the trial with intensive blood pressure lowering (25.6% vs 20%; relative risk, 1.30; P = .05).
Commenting on the study for Medscape Medical News, Craig Anderson, MD, University of Sydney, Australia, who led the INTERACT2 trial, said ATACH-II was "well conducted and extends knowledge."
Professor Anderson pointed out that 80% of ATACH-II patients had intensive blood pressure lowering before randomization and that comparison treatment groups ended up being "very intensive" vs "intensive."
He said the results indicate that "very intensive" blood pressure lowering to systolic less than 120 mmHg does not provide additional benefits but rather potential risks compared with "intensive" blood pressure lowering to a systolic less than 140 mmHg, target as suggested by the INTERACT2 trial."
In addition, ATACH-II confirmed a biological signal on reduced hematoma growth, he noted.
He added that the two trials together suggested "the most desirable beneficial treatment target for blood pressure lowering is systolic less than 140 mmHg." Noting that this is what the guidelines now suggest after INTERACT2, he said, "ATACH-II does not provide data to indicate a change to current guidelines."
He said meta-analysis of trial data will allow more reliable evidence on the relationship of blood pressure-lowering treatment according to time from onset of symptoms and degree of blood pressure reduction. "In particular, pooling analysis of INTERACT2 and ATACH-II trials will better inform clinical practice."
Others More Cautious
Other experts at the conference were more cautious, suggesting that the ATACH-II results may cause some reconsideration about the benefit of blood pressure lowering after ICH.
Kennedy Lees MD, University of Glasgow, United Kingdom, said the ATACH-II trial "undermines slightly the confidence we had in blood pressure lowering from the INTERACT2 trial."
He added: "INTERACT2 came out as a nonsignificant benefit of lowering blood pressure on the primary endpoint but significant on its secondary, but now we're beginning to wonder how true that was, because ATACH-II didn't show any benefit of lowering blood pressure in the acute phase."
Yvo Roos. MD, Academic Medical Centre, Amsterdam, Netherlands, told Medscape Medical News that he was not convinced about blood pressure lowering after ICH.
"In INTERACT2 you end up with a number needed to treat of 34 to prevent one poor outcome which isn't that good. It's not a huge effect. So I wasn't completely surprised to see this result from ATACH," he said.
"We don't treat hypertension acutely in ICH in our hospital as the data isn't that strong and it is also difficult logistically," Dr Roos noted. "ICH patients need to be admitted to a stroke care unit where they can be treated by stroke experts but if they are given IV antihypertensives they usually go to the intensive care unit or coronary care unit where they can deal with the risk of hypotension better. This is taking them away from the stroke specialists. It has been shown that an ICH patient is way better off in a stroke care unit. I think this is more important than lowering blood pressure."
Other experts expressed concern about the last-minute delay to the ATACH-II publication and said that not knowing the reasons for this — and not being able to fully examine the results — made it difficult to comment on any implications for clinical practice.
European Stroke Organisation Conference (ESOC) 2016. Presented May 10, 2016.
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Cite this: ATACH-II: No Benefit of Intensive BP Lowering in ICH - Medscape - May 18, 2016.