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Blood pressure targets in acute intracerebral hemorrhage—no benefit from more intensive treatment
Journal of the American Society of Hypertension
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(2016) 1
Hypertension Highlight BLOOD PRESSURE TARGETS IN ACUTE INTRACEREBRAL HEMORRHAGE—NO BENEFIT FROM MORE INTENSIVE TREATMENT Determining appropriate blood pressure (BP) goals in patients with acute intracerebral hemorrhage (ICH) is a complex and vexing problem facing intensivists, neurologists, and clinical hypertension specialists. Previous observations have suggested that uncontrolled hypertension may be associated with increased hematoma expansion and poor outcome. However, in acute ICH, perfusion of the penumbra of the hematoma and other brain tissue in the setting of potentially increased intracranial pressure may also be important. Management is complicated by the lability of BP that is often seen with acute ICH. In the previously reported INTERACT-2 study, intensive reduction of BP to a goal of <140 mm Hg within 6 hours was associated with a trend toward improvement in the primary outcome of death and disability and a significant, albeit modest, improvement in disability as measured on the ordinal analysis of modified Rankin Score.1 In INTERACT-2, the prerandomization BP was relatively low (most <180 mm Hg), many patients (41%) did not receive the initial antihypertensive therapy until >4 hours from symptoms onset, and target BP was often not achieved within the first hour after initiation. In contrast, the ATTACH-2 study was designed to determine the relative risk and benefit of rapidly achieved intensive versus standard BP control in patients clearly hypertensive at baseline.2 In ATTACH-2, 1000 patients with moderate-sized ICH (mean volume 10.2 cm3) with at least one systolic BP reading of >180 mm Hg and symptom presentation within 4.5 hours were randomly assigned to an intensive systolic BP target of 110–139 mm Hg or a conventional systolic BP target of 140–179 mm Hg. The goal was to achieve BP target quickly and to maintain it for the first 24 hours after randomization. Increasing doses of intravenous nicardipine was the primary mode of therapy with labetalol and other medications added as needed. After 24 hours, BP management was at the discretion of the treating providers. The prespecified primary end point was a composite of death and moderate or severe disability (as measured by modified Rankin score) at 3 months. ATTACH-2 was an international trial and included a large number of Asian patients (55.4%). Mean age of enrolled patients was 61.9 years, and 38.0% were women. Mean systolic 1933-1711/$ - see front matter http://dx.doi.org/10.1016/j.jash.2016.09.003
BP at baseline was 200.6 mm Hg. Especially given the number of sites, the investigators should be commended for the prompt randomization, treatment, and achievement of goal BP in this difficult to study patient population. The mean interval between symptoms onset and randomization was just over 3 hours. The mean systolic BP within the first 2 hours after randomization was 128.9 mm Hg for the intensive treatment group and 141.1 mm Hg in the conventional treatment group. After 3 months, there was no difference in the primary end point of death or moderate-severe disability observed between the intensive and conventional treatment groups (38.7% vs. 37.7%, respectively). Additionally, no significant improvement was seen with intensive therapy in any prespecified subgroup or in any prespecified secondary outcome. There was a modest increase in serious adverse events at 72 hours in the intensively treated group and a more pronounced increased risk of renal adverse events 7 days after randomization in the intensively treated group. After 3 months, the cumulative observed number of serious adverse events was higher in the intensively treated group (25.6% vs. 20.0%). Taken together, the results of these two studies suggest that for most patients with acute ICH, an initial systolic BP goal of 140–179 is appropriate, at least over the first 24 hours. Long term, these patients almost certainly need more aggressive BP control to prevent recurrent events; the timing of that treatment intensification remains to be determined. Michael J. Bloch, MD, FACP, FASH, FSVM, FNLA Department of Medicine University of Nevada School of Medicine Reno, NV, USA Department of Vascular Care Renown Institute for Heart and Vascular Health Reno, NV, USA [email protected]
References 1. Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368:2355–65. 2. Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med 2016; 375(11):1033–43.
-(-)
(2016) 1
Hypertension Highlight BLOOD PRESSURE TARGETS IN ACUTE INTRACEREBRAL HEMORRHAGE—NO BENEFIT FROM MORE INTENSIVE TREATMENT Determining appropriate blood pressure (BP) goals in patients with acute intracerebral hemorrhage (ICH) is a complex and vexing problem facing intensivists, neurologists, and clinical hypertension specialists. Previous observations have suggested that uncontrolled hypertension may be associated with increased hematoma expansion and poor outcome. However, in acute ICH, perfusion of the penumbra of the hematoma and other brain tissue in the setting of potentially increased intracranial pressure may also be important. Management is complicated by the lability of BP that is often seen with acute ICH. In the previously reported INTERACT-2 study, intensive reduction of BP to a goal of <140 mm Hg within 6 hours was associated with a trend toward improvement in the primary outcome of death and disability and a significant, albeit modest, improvement in disability as measured on the ordinal analysis of modified Rankin Score.1 In INTERACT-2, the prerandomization BP was relatively low (most <180 mm Hg), many patients (41%) did not receive the initial antihypertensive therapy until >4 hours from symptoms onset, and target BP was often not achieved within the first hour after initiation. In contrast, the ATTACH-2 study was designed to determine the relative risk and benefit of rapidly achieved intensive versus standard BP control in patients clearly hypertensive at baseline.2 In ATTACH-2, 1000 patients with moderate-sized ICH (mean volume 10.2 cm3) with at least one systolic BP reading of >180 mm Hg and symptom presentation within 4.5 hours were randomly assigned to an intensive systolic BP target of 110–139 mm Hg or a conventional systolic BP target of 140–179 mm Hg. The goal was to achieve BP target quickly and to maintain it for the first 24 hours after randomization. Increasing doses of intravenous nicardipine was the primary mode of therapy with labetalol and other medications added as needed. After 24 hours, BP management was at the discretion of the treating providers. The prespecified primary end point was a composite of death and moderate or severe disability (as measured by modified Rankin score) at 3 months. ATTACH-2 was an international trial and included a large number of Asian patients (55.4%). Mean age of enrolled patients was 61.9 years, and 38.0% were women. Mean systolic 1933-1711/$ - see front matter http://dx.doi.org/10.1016/j.jash.2016.09.003
BP at baseline was 200.6 mm Hg. Especially given the number of sites, the investigators should be commended for the prompt randomization, treatment, and achievement of goal BP in this difficult to study patient population. The mean interval between symptoms onset and randomization was just over 3 hours. The mean systolic BP within the first 2 hours after randomization was 128.9 mm Hg for the intensive treatment group and 141.1 mm Hg in the conventional treatment group. After 3 months, there was no difference in the primary end point of death or moderate-severe disability observed between the intensive and conventional treatment groups (38.7% vs. 37.7%, respectively). Additionally, no significant improvement was seen with intensive therapy in any prespecified subgroup or in any prespecified secondary outcome. There was a modest increase in serious adverse events at 72 hours in the intensively treated group and a more pronounced increased risk of renal adverse events 7 days after randomization in the intensively treated group. After 3 months, the cumulative observed number of serious adverse events was higher in the intensively treated group (25.6% vs. 20.0%). Taken together, the results of these two studies suggest that for most patients with acute ICH, an initial systolic BP goal of 140–179 is appropriate, at least over the first 24 hours. Long term, these patients almost certainly need more aggressive BP control to prevent recurrent events; the timing of that treatment intensification remains to be determined. Michael J. Bloch, MD, FACP, FASH, FSVM, FNLA Department of Medicine University of Nevada School of Medicine Reno, NV, USA Department of Vascular Care Renown Institute for Heart and Vascular Health Reno, NV, USA [email protected]
References 1. Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368:2355–65. 2. Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med 2016; 375(11):1033–43.