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Tatalaksana Tekanan Darah Pada Intracerebral Haemorhage
Tatalaksana Tekanan Darah Pada Intracerebral Haemorhage
in Intracerebral Hemorrhage
Equipoise Resists an Attack
Kenneth Butcher, MD, PhD, FRCP; Magdy Selim, MD, PhD
toma expansion. Although the latter is a biologically plausible ≈10 mL). The ATACH-II trial results suggest that aggressive
hypothesis, this relationship has not been consistently demon- BP reduction during the acute phase of ICH to SBP <140
strated in retrospective or prospective studies, likely reflecting mm Hg is not more effective than a reduction to SBP of 140 to
the fact that hematoma expansion is dependent on multiple 179 mm Hg and that kidney function tests should be followed
factors, in particular the time from symptom onset to diag- closely in patients where SBP is rapidly and aggressively low-
nostic scan, and baseline volume.1 The most effective way ered, given the observed increased frequency of renal-related
to address this clinical equipoise is, therefore, a randomized adverse events.
controlled trial of the 2 different BP management strategies. What are the potential harmful effects of BP reduction,
In the ATACH-II trial (Antihypertensive Treatment of which was indeed effectively accomplished in ATACH-2?
Acute Cerebral Hemorrhage II), 1000 patients were random- Although it has previously been demonstrated that aggres-
ized to a systolic BP (SBP) target of 110 to 139 mm Hg or sive BP reduction is not associated with a decrease in cerebral
140 to 179 mm Hg, after the Data Safety Monitoring Board– blood flow,4 it is possible that the nicardipine-associated drop
recommended trial suspension on the basis of a futility exceeded the threshold at which perfusion is maintained in
analysis.2 Despite a robust and early difference in achieved most patients. There is also some evidence that small areas
BP between the 2 groups, the 90-day mortality and dis- of ischemic injury, visible only with diffusion-weighted mag-
ability rate was unaffected (38.7% versus 37.7%; P=0.84). netic resonance imaging, do develop in some ICH patients
The reasons for this lack of treatment effect are not clear. subacutely.5 Although not conclusive, these data also sug-
There was no effect on the frequency of hematoma expan- gest that the diffusion-weighted magnetic resonance imag-
sion, although the trend was in favor of more aggressive ing lesions may be associated with BP reduction. This raises
BP reduction (18.9% versus 24.4%; P=0.09). Conversely, the possibility of a mixed benefit/harm effect in the overall
aggressive BP lowering did not result in more early neu- population, that is, attenuation of hematoma growth in some
rological deterioration or treatment-related serious adverse patients and ischemic injury in others. The absence of diffu-
events within 72 hours of treatment, as determined by the sion-weighted magnetic resonance imaging and blood flow
investigators (1.6% versus 1.2%; P=0.59). There was, how- imaging in ATACH-II, however, makes it impossible to con-
ever, an increased frequency of renal adverse events within firm or reject this hypothesis.
72 hours (9.0% versus 4.0%; P=0.0002). Although the treat- The argument for a mixed benefit/harm effect would be more
ment duration was only 24 hours, after which all patients compelling if the observed reduction in hematoma expansion was
were treated in the same manner, this may potentially be significant or even if the point estimates of the treatment effect
related to renal hypoperfusion. size was greater. What is apparent is that hematoma expansion
How do the ATACH-II results inform practice? It does can occur despite aggressive BP reduction. This disappointing
seem that in the majority of patients, aggressive SBP reduc- effect on hematoma expansion was seen in both ATACH-II and
tion <140 mm Hg has no effect on 90-day functional outcome the INTERACT-II trials (the Second Intensive Blood Pressure
Received September 6, 2016; final revision received September 24, 2016; accepted October 3, 2016.
From the Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada (K.B.); and Stroke Division, Department of
Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (M.S.).
Correspondence to Magdy Selim, MD, PhD, Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Ave,
Palmer 127, Boston, MA 02460. E-mail mselim@bidmc.harvard.edu
(Stroke. 2016;47:3065-3066. DOI: 10.1161/STROKEAHA.116.015060.)
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.116.015060
3065
3066 Stroke December 2016
Reduction in Acute Cerebral Haemorrhage Trial).6 In the latter Butcher has received grant-in-aid funding from the Heart and Stroke
trial, this may have been related to the fact that BP targets were Foundation of Canada to complete a blood pressure–lowering trial in
intracerbral hemorrhage patients. He also has grant funding from the
not achieved within 1 hour in 66% of the patients randomized to Canadian Institutes for Health Research and holds a Canada Research
the aggressive treatment target arm. This does not seem to be the Chair.
case in ATACH-II, however, where this was accomplished in 88%
of patients in the aggressive treatment arm. One possibility is that Disclosures
even the effective BP reduction seen in ATACH-II was too late Dr Butcher has received speaker’s fees and served on advisory boards
to have an effect on hematoma expansion. The initial ATACH-II for Boehringer Ingelehim, Bayer, and BMS/Pfizer. The other author
design had an inclusion window of 3 hours from symptom onset, reports no conflicts.
and this was later expanded to 4.5 hours.7 The rationale for the
narrower window than that used in INTERACT-II was that the References
probability of hematoma expansion decreases with time after 1. Broderick JP, Diringer MN, Hill MD, Brun NC, Mayer SA, Steiner
symptom onset. It may, therefore, be that if a significant treat- T, et al; Recombinant Activated Factor VII Intracerebral Hemorrhage
Trial Investigators. Determinants of intracerebral hemorrhage growth:
ment effect is to be seen, BP reduction will need to begin even an exploratory analysis. Stroke. 2007;38:1072–1075. doi: 10.1161/01.
earlier, potentially in the prehospital setting. STR.0000258078.35316.30.
There are now 2 large randomized controlled trials of 2. Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL,
et al; ATACH-2 Trial Investigators and the Neurological Emergency
aggressive versus conservative BP management, both of Treatment Trials Network. Intensive blood-pressure lowering in patients
which had negative primary end points. Nonetheless, acute with acute cerebral hemorrhage. N Engl J Med. 2016;375:1033–1043.
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