Jury still out on early BP lowering after stroke


27 Feb 2019

Early intensive blood pressure management reduces the risk of intracranial haemorrhage after thrombolysis but does not improve post-stroke recovery, an international trial reports.

The phase 3 open-label multicentre Enhanced Control of Hypertension and Thrombolysis Stroke (ENCHANTED) trial randomised 2196 patients who were eligible to receive alteplase to an intensive BP lowering group (n=1018; 130-140 mm Hg within 1 hour) or guideline recommended BP lowering (n=1115; target 180mm Hg over 72 hours) within 6 hours of having an acute ischaemic stroke.

Results showed that the trial’s primary outcome of an improvement in functional status at 90 days, as measured by modified Rankin Scale  (mRS) scores, did not differ between the treatment groups [OR 1.01 95% CI 0.87-1.17].

However, the rate of intracranial haemorrhage (ICH) was significantly less in the patients randomised to the intensive treatment group (14.8% vs 18.7%), reported lead researcher Craig Anderson, Professor of Neurology at the University of New South Wales, Sydney, and executive director of the George Institute for Global Health, during a late breaking session at the International Stroke Conference held in Honolulu. The findings were published simultaneously in The Lancet.

The study authors said that while the results might not support a major shift towards intensive BP lowering in people with mild to moderate acute ischaemic stroke receiving alteplase treatment, they should reassure clinicians that the practice is not associated with an increased risk of death or disability.

“Many clinicians are concerned that rapid blood pressure reductions in the absence of mechanical or pharmacological reperfusion might worsen cerebral ischaemia from potential hypoperfusion with compromised autoregulation and collateral flow,” they wrote.

“Such treatment could potentially reduce the risk of major intracranial haemorrhage, but further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering  in cases of hyperacute acute ischaemic stroke,” they added.

Evidence is somewhat ‘disenchanting’

In an accompanying editorial, neurologists Else Charlotte Sandset from Oslo University Hospital, Norway, and Urs Fischer from the University Hospital Bern, Switzerland, stated that the study adds important evidence to an ongoing  debate over whether the benefits of intensive BP lowering early after the onset of acute ischaemic stroke are offset by potential harms.

However, they also described the new evidence as “somewhat disenchanting” because it showed  a neutral effect of blood pressure lowering on functional outcome in acute stroke.

“This finding might be related to the smaller than envisaged difference in blood pressure between the groups, or the inclusion of mainly patients with mild-to-moderate stroke, who are less likely to develop symptomatic intracerebral hemorrhage,” they wrote.

They also suggested that the BP reduction target was too low, “causing hypoperfusion in the intensive treatment group and neutralizing favorable outcomes resulting from reduced intracranial hemorrhage.”

The pragmatic design of the trial and its broad inclusion criteria could have also contributed to the trials neutral results.

They suggest that imaging should be implemented in future randomised controlled trials of blood pressure lowering in order to “better understand the underlying mechanisms of benefit or harm related to treatments under investigation”.

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