Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage

Abstract

Background Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage. Methods We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm3) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments. Results Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P = 0.002). Conclusions The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565.)

CM352 Reduces Brain Damage and Improves Functional Recovery in a Rat Model of Intracerebral Hemorrhage

“…Strategies addressing hematoma expansion by lowering blood pressure,7 surgical hematoma removal,8 reversal of anticoagulants,3 or hemostatic therapy with rFVIIa9 have provided evidence of reduced hematoma growth, but results regarding long‐term therapeutic benefit have been mainly disappointing 4. Moreover, to our knowledge, only a few preclinical studies have been conducted to assess the effects of the pharmacological modulation of hematoma growth 6.…”

“…To date aggressive blood pressure reduction,7 early neurosurgical intervention,8 and hemostatic therapy with recombinant active factor VII (rFVIIa)9 have failed to improve survival or functional outcome after ICH in unselected patients. Because hyperfibrinolysis is an important contributor to major bleeding events and has been associated with ICH,10 clinical trials are currently being conducted to assess the benefits of antifibrinolytic therapy (tranexamic acid [TXA]) to reduce hemorrhage and improve ICH outcome 11…”

Evaluation of Acute Kidney Injury and Mortality After Intensive Blood Pressure Control in Patients With Intracerebral Hemorrhage

“…Although other trials, such as SPRINT (Systolic Blood Pressure Intervention Trial), have also found significant increases in AKI on the basis of intensive SBP reduction7 and secondary analysis of the ATACH trial18 and supplementary analysis of the ATACH 2 trial6 showed greater incidence of AKI in patients treated with intensive SBP control, this is the first trial to define a threshold value for SBP reduction (ie, maximum SBP reduction) in ICH that is associated with in‐hospital AKI.…”

“…The ATACH 2 trial complicated the benefit of intensive SBP reduction in acute ICH by demonstrating a significant increase in adverse renal events in patients randomized to intensive antihypertensive therapy 6. We investigated this association and found that aggressive SBP reduction may play a role in the development of in‐hospital AKI.…”

“…As a result, this goal was adopted by the American Heart Association/American Stroke Association recommendations for acute ICH management 5. However, this blood pressure goal has been disputed by the more recent ATACH 2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage 2) trial that compared an intensive SBP goal (<140 mm Hg) to a standard SBP goal (140–179 mm Hg) and found no improvement in primary outcome 6. Moreover, the ATACH 2 trial reinforced a growing body of evidence7 that suggested that intensive SBP reduction might lead to higher rates of adverse renal events.…”