Intracerebral Hemorrhage: Strict BP Control Not to Blame for Pinprick Brain Lesions
The acute intensive blood pressure (BP) lowering recommended after intracerebral hemorrhage (ICH) did not increase small-volume infarcts compared with looser control in a small randomized trial.
Of 79 patients in the ICHADAPT-2 study, a systolic BP target under 140 mm Hg yielded similar likelihood of diffusion-weighted imaging (DWI) lesions 48 hours after ICH compared with a target of less than 180 mm Hg (31% vs 38%; OR 0.74, 95% CI 0.12-4.64), according to a group led by Ken Butcher, MD, PhD, of the University of New South Wales and Prince of Wales Hospital in Sydney.
Similarly, no between-group difference emerged with regards to the number of DWI lesions (median 1-1.5 per person) or total DWI lesion volume (typically under 1 mL) on brain MRI, with the majority being small volume lesions. Nor did the more intensive target increase incident lesions on repeat MRI at 7 and 30 days, "despite a statistically significant, rapid, and sustained" systolic BP reduction, the researchers reported in JAMA Neurology.
"These findings do not support the hypothesis that intensive BP treatment precipitates ischemic injury after ICH," Butcher and colleagues concluded.
Their ICHADAPT-2 study supported current guideline recommendations for a target systolic BP (SBP) range of 130-140 mm Hg in acute ICH.
The concern with this approach has been that tighter BP control might cause a drop in cerebral perfusion pressure and lead to ischemic injury in acute ICH. Whether the asymptomatic DWI lesions commonly seen in this setting cause long-term morbidity and mortality has also not been clear.
"The mechanism of DWI lesions in acute ICH is perhaps not primarily related to relative cerebral hypoperfusion, and the benefits of prevention of hematoma expansion and the negative effects of severe hypertension on the brain outweigh the risk of rapid SBP reduction to a normal range in this setting," wrote Jessica Magid-Bernstein, MD, PhD, of Yale School of Medicine in New Haven, Connecticut, and Santosh Murthy, MD, MPH, of Weill Cornell Medicine in New York City.
Their accompanying editorial noted, though, that the study did not account for cerebral small-vessel disease, which has been linked to DWI lesions. "From a mechanistic standpoint, underlying cerebral small-vessel disease is purported to cause DWI lesions. Whether intensive BP lowering contributes to these lesions is highly contested."
"It is therefore important to acknowledge that personalized BP targets based on physiological data may be an optimal strategy for post-ICH BP management, but this approach is not yet feasible for broad clinical application," Magid-Bernstein and Murthy wrote.
Study authors also cautioned that they had been unable to meet their enrollment target after 10 years; ICHADAPT-2 was halted after the loss of clinical equipoise following the announcement of the INTERACT3 trial results favoring a care bundle protocol for ICH that included targeting systolic BP to less than 140 mm Hg.
The trial ended up with over half of the 162 randomized patients not getting the brain MRI needed to assess the primary endpoint -- with clear selection bias indicated by patients with larger ICH volumes and more severe neurological disability less likely to undergo DWI at 48 hours.
"Ongoing uncertainties about the true frequency of DWI lesions after ICH, their association with acute interventions, and outcomes may be addressed in the future if routine early MRI scans become part of ongoing ICH registries and practice guidelines," Butcher's group suggested.
"While a role for acute BP reduction, perhaps acting synergistically with multiple factors, in the mechanism of DWI changes cannot be excluded in all patients, it is likely irrelevant in the majority of cases," the group maintained in the meantime.
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