BY ED SUSMAN
HONOLULU—Functional outcomes after an ischemic stroke treated with clot-busting drugs was not helped by a program of intensive blood pressure lowering when compared with standard-care hypertension treatment, researchers reported here at the 2019 International Stroke Conference, sponsored by the American Stroke Association.
The treatment effect at 90 days seen in the Enhanced Control of Hypertension and Thrombolysis Stroke (ENCHANTED) study was minimal and not significant, reported Craig Anderson, MD, PhD, professor of neurology and epidemiology at the University of New South Wales in Sydney, Australia, and executive director of the George Institute in China.
In the unadjusted primary outcome, the odds ratio of having a better shift in the modified Rankin Scale (mRS) scores was 1.01 (p=0.8702), Dr. Anderson reported in his late-breaker, oral presentation. When researchers adjusted the results to account for baseline characteristics, the results weren't much different (p=0.7171), he said. And when the outcomes were adjusted for per-protocol adherence, there still was a neutral result (p=0.5141), he said.
On the other hand, the key safety outcome of the trail was positive, as bleeding in the brain, a worrisome consequence of the use of tissue plasminogen activator (tPA) in breaking up clots, was significantly reduced in the ENCHANTED population, Dr. Anderson said. Among the 1,081 patients treated with intensive blood pressure lowering 59 patients experienced intracranial hemorrhage—approximately 5.5 percent of that group—while 100 of the 1,115 patients assigned to standard therapy for blood pressure control, or 9 percent, experienced intracranial hemorrhage (p=0.0017).
"This study clearly shows intensive blood pressure lowering has the potential to make thrombolysis treatment safer by reducing the risk of serious bleeding in the brain," Dr. Anderson said.
Possibly confounding the results of the study was that blood pressure lowering was substantial in both groups. Although the goal in the standard care group was to lower blood pressure to 180 mmHg over a three-day period, clinicians were able to reduce blood pressure in that group to a mean of 144 mmHg, while in the patients on the intensive treatment, where the aim was to lower systolic blood pressure below 140 mmHg, the mean blood pressure was 139 mmHg.
"These findings also highlight the need for more research to better understand the underlying mechanisms of benefit and harm of early intensive blood pressure lowering in the patients receiving modern reperfusion therapy with thrombolysis and devices, given that the reduction in brain hemorrhage failed to translate into improvements in overall recovery for patients," said Tom Robinson, MD, head of the Cardiovascular Research Centre at the University of Leicester in the United Kingdom, and a co-author of the ENCHANTED trial who also presented the results.
The large international clinical trial results, presented at the meeting, were simultaneously published in The Lancet.
In commenting on the study, Ralph L. Sacco, MD, MS, FAHA, FAAN, chairman of neurology at the Miller School of Medicine at the University of Miami in Florida, and president of the AAN, told Neurology Today At the Meetings: "These were all patients treated with intravenous tPA within 4.5 hours, so it was a normal treatment, but we wanted to know if we should be more aggressive in the early control of blood pressure versus what the guidelines currently suggest, which is to get the blood pressure down to less than 180 mmHg. The guidelines suggest that if you get the blood pressure below 180 mmHg, then it may be safe to give tPA."
"The question was could we do even better to stop bleeding if we lowered the blood pressure even more tightly controlled to 130–140 mmHg further," Dr. Sacco said. "While there was no difference in disability at 90 days, there was less bleeding—even though there was just a small difference in blood pressure it still made a difference in bleeding. The most feared complication of using tPA is intracranial hemorrhage and lowering blood pressure seemed to lessen this complication in the ENCHANTED study."
"In this trial the guideline group did better in lowering blood pressure than you would have expected. It seems that people are being more aggressive with blood pressure control, and that may be why we didn't see a difference in disability outcomes," he said. "The benefit we saw in safety did not seem to translate into benefit in function."
Dr. Sacco cautioned, however, that one should be cautious in delaying treatment with tPA in order to get the patient's blood pressure lower. "At this point, I would say there probably is no reason to change the guidelines, especially since people seem to be practicing aggressive blood pressure lowering any way," he said.
Dr. Anderson received a research grant from the National Health and Medical Research Council of Australia and research funds from Takeda for support of the trial in China. He serves on the advisory boards of Boehringer Ingelheim and Amgen.
LINK UP FOR RELATED INFORMATION:
ISC Abstract LB6: Anderson C, Robinson T, et al, for the ENCHANTED Investigators. Main results of the enhanced control of hypertension and thrombolysis stroke study (enchanted) of the early intensive blood pressure control after thrombolysis.