Affiliation: 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
Pubmed link to the work reviewed:
https://www.ncbi.nlm.nih.gov/pubmed/27276234
Comment:
The results of previous randomized trials, especially INTERACT-2, have shown that early intensive blood pressure lowering in patients with spontaneous intracerebral hemorrhage (ICH) may improve outcome [1]. Therefore, reaching systolic blood pressure (SBP) of <140 mmHg within the first 6 hours from the onset of symptoms is suggested by the current European Stroke Organization Guidelines (quality of evidence: moderate; strength of recommendation: weak) [2]. The recently published Antihypertensive Treatment of Acute Cerebral Hemorrhage II trial (ATACH-II) was designed to investigate an even more aggressive approach [3]. Patients ≤4.5 hours from the onset of spontaneous supratentorial ICH (hematoma volume <60 cm3, Glasgow Coma Scale score ≥5, SBP ≥180 mmHg) were randomly assigned to receive intravenous nicardipine in order to achieve within 2 hours SBP of 110-139 mmHg (intervention) or 140-179 mmHg (standard care according to the American Stroke Association Stroke Council guidelines published in year 2007 [4]) and maintain it for 24 hours. The trial was stopped for futility after enrolling 1000 (56% Asian, 29% white, 13% black) of 1280 planned participants. Target blood pressure in the intervention group was reached by 86% and then maintained for 24 hours by 84% of patients. There were no differences in the occurrence of early serious adverse events. The primary endpoint of being dead at 3 month or having at least moderately severe disability (modified Rankin Scale score of ≥4) was observed in 39% and 38% of patients, respectively. Adjustment for confounders as well as subgroup analyses did not reveal any significant differences between both treatment arms. On the whole, the study does not support intensive lowering of very high SBP in ICH but, due to several methodological differences, it also does not have the strength to fully question conclusions from the previous trials. For example, patients enrolled to INTERACT-2 had baseline SBP of 150-220 mmHg and the target SBP of <140 mmHg was to be maintained for 7 days [5].
References:
1. Tsivgoulis G, Katsanos A, Butcher K, Boviatsis E, Triantafyllou N, Rizos I et al. Intensive blood pressure reduction in acute intracerebral hemorrhage. Neurology 2014;83:1523–1529.
2. Steiner T, Al-Shahi Salman R, Beer R, Christensen H, Cordonnier C, Csiba L et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke 2014;9:840–855.
3. Qureshi A, Palesch Y, Barsan W, Hanley D, Hsu C, Martin RL et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med 2016; epub ahead of print.
4. Broderick J, Connolly E, Feldmann E, Hanley D, Kase C, Krieger D et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults. Circulation 2007;116:e391–413.
5. Anderson C, 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;368:2355–2365.
Key points:
1. Very aggressive systolic blood pressure lowering with intravenous nicardipine after spontaneous supratentorial intracerebral hemorrhage (target 110-139 mmHg, treatment initiated within 4.5 hours from the onset) did not prove to reduce the risk of death or moderately severe disability at 3 months.
2. The results of ATACH-2 trial do not support findings from the previous randomized trials, which may be caused by several methodological differences.
3. A less aggressive approach to lower blood pressure after spontaneous intracerebral hemorrhage as suggested by the European Stroke Organization Guidelines 2014 appears still reasonable.