INTERACT2 challenges ‘longstanding dogma’ of ICH management
medwireNews: The results of INTERACT2 show that blood pressure in patients with acute intracerebral hemorrhage (ICH) can be reduced to within the normotensive range without excess adverse effects.
Moreover, intensive treatment to a systolic blood pressure target of less than 140 mmHg resulted in better 90-day outcomes, compared with treating to the current guideline target of less than 180 mmHg, investigator Craig Anderson (George Institute for Global Health, Sydney, Australia) reported at the European Stroke Conference in London, UK.
INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2) in fact just missed its primary endpoint of a reduction in death or disability (modified Rankin Scale [mRS] 3-6). This outcome occurred in 52.0% of 1382 patients treated to an intensive target, versus 55.6% of 1412 patients in the control group, giving an odds ratio of 0.87 with a 95% confidence interval of 0.75-1.01.
But as Anderson pointed out, this means one can say with 94% confidence that there is a significant benefit with intensive blood pressure reduction. The number needed to treat to prevent one patient dying or becoming disabled would be 25, he added.
In line with this, intensive treatment had a significant benefit on the trial's "key secondary" endpoint of shift analysis of mRS scores, an analysis perceived by many to be more powerful than assessing a dichotomized outcome, because it accounts for changes across the whole range of outcomes.
And Anderson noted that INTERACT2 was an active comparator trial, in which all patients were treated at least to the guideline target. "So it's quite probable that the full benefits of blood pressure lowering will be greater in routine care where only the extremes of blood pressure are treated, if at all."
Also, Anderson stressed that the trial "debunks the longstanding neurological dogma" that blood pressure reduction is likely harmful in ICH patients. Acute neurologic deterioration within the first 24 hours occurred in similar proportions of the intensive and control treatment groups, at 14.5% and 15.1%, respectively, while a corresponding 0.5% and 0.6% developed severe hypotension, and 11.9% and 12.0% died.
Most (90.1%) patients in the intensive treatment group received at least one intravenous antihypertensive agent during the first 24 hours, compared with 42.9% of the control group. The agents used were left to the discretion of the treating physicians.
"Given that the treatment is low-cost, relatively simple to implement and widely applicable, this should become the standard of care in hospitals all over the world," Anderson concluded.
Further to go?
Although INTERACT2 has produced positive results for an important question, that may not be the end of the story, because several issues surrounding the timing and target of blood pressure treatment remain unclear.
Anderson said that around 4 hours passed between ICH onset and randomization, after which it took another few hours to control blood pressure. Speaking to medwireNews, co-investigator Emma Heeley (also from the George Institute) explained that clinicians often encountered problems with timely access to drugs, "so what we want to do is try and train everyone up so they're ready, like with thrombolysis, so they've got a box ready to go."
There are plans in discussion for INTERACT3, she said - a cluster randomized trial looking at the implementation of blood pressure lowering.
And in the meantime, given that the 140 mmHg systolic blood pressure target is largely based on consensus, rather than evidence, the team plans to analyze the achieved blood pressures in INTERACT2 in relation to patient outcomes. However, Heeley noted that there were few blood pressures below 130 mmHg. "I think doctors were a bit conservative," she commented.
But she believes the INTERACT2 findings should give doctors participating in INTERACT3 the confidence to treat aggressively and achieve the blood pressure target fast. INTERACT3 will include treatment time targets, so, Heeley hopes, patients will achieve blood pressure control within an hour of randomization.
The INTERACT2 findings were simultaneously published in The New England Journal of Medicine.
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