Acute Blood Pressure Management in Intracerebral Hemorrhage

There are 2 competing rationales for acute blood pressure (BP) management in primary intracerebral hemorrhage (ICH). A conservative approach is predicated on the possibility that cerebral blood flow is passively dependent on perfusion pressure, whereas an aggressive approach has been hypothesized to improve outcomes via a reduction in early hematoma expansion. Although the latter is a biologically plausible hypothesis, this relationship has not been consistently demonstrated in retrospective or prospective studies, likely reflecting the fact that hematoma expansion is dependent on multiple factors, in particular the time from symptom onset to diagnostic scan, and baseline volume. The most effective way to address this clinical equipoise is, therefore, a randomized controlled trial of the 2 different BP management strategies. In the ATACH-II trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage II), 1000 patients were randomized to a systolic BP (SBP) target of 110 to 139 mm Hg or 140 to 179 mm Hg, after the Data Safety Monitoring Board– recommended trial suspension on the basis of a futility analysis. Despite a robust and early difference in achieved BP between the 2 groups, the 90-day mortality and disability rate was unaffected (38.7% versus 37.7%; P=0.84). The reasons for this lack of treatment effect are not clear. There was no effect on the frequency of hematoma expansion, although the trend was in favor of more aggressive BP reduction (18.9% versus 24.4%; P=0.09). Conversely, aggressive BP lowering did not result in more early neurological deterioration or treatment-related serious adverse events within 72 hours of treatment, as determined by the investigators (1.6% versus 1.2%; P=0.59). There was, however, an increased frequency of renal adverse events within 72 hours (9.0% versus 4.0%; P=0.0002). Although the treatment duration was only 24 hours, after which all patients were treated in the same manner, this may potentially be related to renal hypoperfusion. How do the ATACH-II results inform practice? It does seem that in the majority of patients, aggressive SBP reduction <140 mm Hg has no effect on 90-day functional outcome or mortality. This may be related in part to the fact that the occurrence of hematoma expansion in even the conservatively treated ATACH-II patients (24%) was lower than that seen in the original observational studies describing hematoma expansion (38%). This, in turn, likely reflects the fact that baseline hematoma volumes were small in ATACH-II (median volume ≈10 mL). The ATACH-II trial results suggest that aggressive BP reduction during the acute phase of ICH to SBP <140 mm Hg is not more effective than a reduction to SBP of 140 to 179 mm Hg and that kidney function tests should be followed closely in patients where SBP is rapidly and aggressively lowered, given the observed increased frequency of renal-related adverse events. What are the potential harmful effects of BP reduction, which was indeed effectively accomplished in ATACH-2? Although it has previously been demonstrated that aggressive BP reduction is not associated with a decrease in cerebral blood flow, it is possible that the nicardipine-associated drop exceeded the threshold at which perfusion is maintained in most patients. There is also some evidence that small areas of ischemic injury, visible only with diffusion-weighted magnetic resonance imaging, do develop in some ICH patients subacutely. Although not conclusive, these data also suggest that the diffusion-weighted magnetic resonance imaging lesions may be associated with BP reduction. This raises the possibility of a mixed benefit/harm effect in the overall population, that is, attenuation of hematoma growth in some patients and ischemic injury in others. The absence of diffusion-weighted magnetic resonance imaging and blood flow imaging in ATACH-II, however, makes it impossible to confirm or reject this hypothesis. The argument for a mixed benefit/harm effect would be more compelling if the observed reduction in hematoma expansion was significant or even if the point estimates of the treatment effect size was greater. What is apparent is that hematoma expansion can occur despite aggressive BP reduction. This disappointing effect on hematoma expansion was seen in both ATACH-II and the INTERACT-II trials (the Second Intensive Blood Pressure Acute Blood Pressure Management in Intracerebral Hemorrhage Equipoise Resists an Attack