What's the ideal blood pressure target after ischemic stroke?
What's the ideal blood pressure target after ischemic stroke?
Blood pressure often rises during acute ischemic strokes, in what is widely held to be a natural protective mechanism: increased blood pressure pushes more blood through and around stenotic blood vessels into areas of injured, oxygen-starved brain. This process is hypothesized to reduce further ischemic injury that would occur if blood pressure were to remain at baseline. Within about 10 days after an acute ischemic stroke, blood pressure often spontaneously falls by as much as 20/10 mm Hg.
This observed phenomenon supports a permissive approach to hypertension during treatment of acute strokes, that is, allowing a systolic blood pressure higher than normal. However, allowing blood pressure to rise too high brings an increased risk for recurrent stroke.
Registry data shows a U-shaped curve in risk, suggesting extremes in blood pressure should be avoided—patients with systolic BP >200 mm Hg or <130 mm Hg did measurably worse after their acute strokes. But there’s been surprisingly little data from randomized trials to identify more precise targets in the middle:
The MAPAS trial (2019) suggested rapid lowering of blood pressure in acute ischemic stroke was unhelpful, a target of 161-180 mm Hg might be beneficial, and pressures 181-200 mm Hg resulted in more intracranial hemorrhage.
A 2015 meta-analysis of 13 randomized trials enrolling >12,000 patients suggested that active blood pressure management after ischemic strokes had little effect on eventual outcomes, and that delaying blood pressure control for three days did not lead to worse outcomes (death or disability).
The result of this imprecision (or possibly absence of benefit from more precise targets) is wide practice variation in management of hypertension in acute ischemic stroke, with target systolic blood pressures typically varying between 140 - 180 mm Hg.
That’s partly because since the effect sizes are likely small (as suggested by the meta-analysis above), an adequately powered randomized trial would be large and expensive. And if the effect size is small enough, no conceivable trial would ever find it.
What about blood pressure control after thrombectomy?
The advent of thrombectomy for acute ischemic stroke has produced new questions regarding optimal blood pressure control.
After thrombectomy, it has been proposed that reducing blood pressure might reduce the rate of hemorrhagic conversion or edema. Clinical guidelines from the American Heart Association, American Stroke Association and the European Stroke Organisation have advised BP targets between 130 and 185 mm Hg.
Unlike after un-reperfused ischemic stroke, some early data suggested lower BP targets could improve outcomes post-thrombectomy.
Those early data now appear to have been largely refuted by multiple randomized trials showing no benefit (and potential harm) from intensive blood pressure control after endovascular reperfusion for acute ischemic stroke:
In the OPTIMAL-BP randomized trial (JAMA 2023), 306 patients were randomized to intensive BP control (<140 mm Hg) or permissive (140-180 mm Hg) for 24 hours after successful endovascular therapy for acute ischemic stroke. Those randomized to the higher target had improved rates of functional independence at 3 months (54% vs 39%). The trial was planned for >660 patients, but was stopped early due to a clear harm signal with intensive BP control.
The BEST-II trial (JAMA 2023) was a phase 2 trial intended to assess the likelihood (or futility) of finding a benefit in a future trial for aggressive BP control after thrombectomy. It only enrolled 120 patients, but suggested it was only 25% likely that intensive BP control (to a target <140 mm Hg) could feasibly be shown in a future trial to produce better outcomes than a target of <180 mm Hg.
ENCHANTED2/MT (Lancet 2022) also showed harm with intensive BP control after thrombectomy among 800 patients, and was terminated early.
In BP-TARGET, intensive BP control did not reduce hemorrhagic transformation after thrombectomy, among 324 patients.
The pressure is off (you)
Significant evidence exists to suggest that treating blood pressure anywhere within reasonable permissive targets (e.g., 140-180 mm Hg) after acute ischemic stroke (post-thrombectomy or not) might result in equivalent outcomes. Blood pressures above or below this range are more likely to be harmful. Vasopressors are sometimes used to support patients’ BP into the target range, which is well-supported physiologically despite the absence of evidence supporting the practice.
A patient’s BP target could be more precisely individualized based on the baseline pre-stroke blood pressure, if known—but there’s no data to strongly advise that.
The effect sizes appear small enough that very large randomized trials would be required to refine these targets any more precisely (if that is possible).
It’s good news for care teams, who can feel confident they’re delivering high quality post-stroke care even while a patient’s blood pressure is fluctuating within a reasonable (permissively elevated) range.
Read more:
BEST-II (JAMA 2023)
ENCHANTED2/MT (Lancet 2022)
BP-TARGET (Lancet Neurology 2021)