But major limitations prevented firm conclusions in ENCHANTED trial
HONOLULU -- Intensive blood pressure lowering for acute ischemic stroke patients eligible for thrombolytics didn't improve functional outcomes compared with standard management, the ENCHANTED trial showed.
Modified Rankin Scale (mRS) scores were not shifted toward better function by targeting 130-140 mm Hg systolic pressure in the first hour after presentation compared with the standard limit of 180 mm Hg (OR 1.01, P=0.87). Similar findings emerged whether per protocol or adjusted for deviations and across stroke severity quartiles.
There was significantly less intracranial hemorrhage, though, in the intensively managed group (14.8% vs 18.7%, OR 0.75, P=0.0137), Craig Anderson, MD, PhD, of the University of Sydney, Australia, reported here at the American Heart Association's International Stroke Conference and online in The Lancet.
Mortality, poor outcome, length of stay, and overall serious adverse events were similar between groups.
While intensive management was safe, the trial provided no evidence to support a major change in the guidelines, Anderson told attendees at the late-breaking clinical trial session.
Nor did it settle the question of optimal blood pressure in acute stroke, the researchers noted, due to several major limitations:
- There was only a 6 mm Hg difference pressure between groups in achieved blood, averaging 144 mm Hg with intensive lowering versus 150 with standard care in the first 24 hours.
- Most strokes were mild to moderate and few cases involved symptomatic intracerebral hemorrhage or proceeded to endovascular therapy.
- The open-label design left potential for bias.
- Generalizability was questionable, because most participants were from China and elsewhere in Asia, where intracranial atheroma and cerebral small vessel disease are bigger concerns than elsewhere in the world.
"When one thinks of the issues of hemodynamic compromise and hemorrhagic transformation, one thinks about much more severe strokes. So you wonder about the ability to see a difference," commented Bruce Ovbiagele, MD, of the University of California, San Francisco.
When combined with the modest blood pressure differential, "perhaps it's not so much of a surprise that we didn't see much of a benefit," he added. As to the optimal management strategy in acute stroke, "it's definitely still an open question."
The prospective, open-label, blinded-endpoint trial included 2,227 patients eligible for alteplase (Activase) or treated for an acute ischemic stroke less than 4.5 hours after onset and who had systolic blood pressure of at least 150 mm Hg.
These patients were randomized within 6 hours of stroke onset to intensive blood pressure lowering to 130-140 mm Hg systolic within 1 hour or guideline-directed blood pressure management to less than 180 mm Hg systolic, both for 72 hours atop background optimal care.
The findings follow negative findings in the RIGHT-2 trial for blood pressure management with nitroglycerin in the very early phase of stroke, administered en route to the hospital.
The trial was funded by the Australian National Health and Medical Research Council and the Stroke Association. Other funding came from the National Council for Scientific and Technological Development of the Brazil Ministry for Health, Welfare and Family Affairs of the Republic of Korea, and Takeda.
Anderson disclosed grant support from the National Health and Medical Research Council of Australia and from Takeda for conduct of the study in China, as well as financial relationships with Amgen, Boehringer Ingelheim, and Takeda.
Ovbiagele disclosed no relevant relationships with industry.
Source Reference: Anderson CS, et al "Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial" Lancet 2019. DOI: 10.1016/S0140-6736(19)30038-8.
Read the original article on Medpage Today: Tighter BP Control No Better in Acute Stroke