Blood pressure reduction for acute intracerebral hemorrhage: How low can you go?

Introduction: Intracerebral hemorrhage (ICH) is associated with a high mortality rate (30%-50%) and substantial disability among survivors and has been called the most devastating form of stroke [1,2]. Over the past decade, large clinical trials of surgical hematoma evacuation and ultra-early hemostatic therapy did demonstrate consistently improved outcomes [3,4]. Thus, effective medical treatments for ICH are long overdue. Severe hypertension is common during the acute phase of ICH. However, little is known about the relative risks and benefi ts of reducing blood pressure (BP) aggressively during the acute phase of bleeding. Elevated BP after ICH is associated with poor outcome [5-10], and recent nonrandomized studies suggest that early lowering of BP is safe and feasible in hypertensive patients with ICH [11-14]. Theoretically, the benefi ts of early BP control might include a reduction in active bleeding and ICH volume growth during the fi rst 6 hours after hemorrhage and decreased tissue edema and intracranial hypertension in the days that follow. After decades of little work in this area, two recent randomized controlled trials have sought to shed light on the issue of optimal BP control during the acute phase of ICH. The study of Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) is currently evaluating nicardipine infusion for control of systolic BP reduction. The authors used an uncontrolled escalating dose-tier design pushing the target systolic BP from 170-200 mm Hg in tier 1, to 140-170 mm Hg in tier 2, and to 110-140 mm Hg in tier 3 [12]. The preliminary results of this US multicenter study indicate that BP reduction to these levels within 6 hours of onset is safe and feasible; however, the fi nal results have yet to be published (A. Quereshi, personal communication). The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) is the other large trial designed to evaluate aggressive BP reduction during the acute stage of ICH [15]. To our knowledge, this international collaboration is the fi rst published multicenter randomized controlled trial of acute BP reduction after ICH. Aims: To assess the safety and effi cacy of early lowering of elevated BP after acute ICH, as a run-in phase to a larger trial. Methods: The authors enrolled 404 patients who had acute spontaneous ICH diagnosed by CT within 6 hours of onset, elevated systolic BP (150-220 mm Hg), and no defi nite indication or contraindication to early intensive lowering of BP. Patients were randomly assigned to intensive BP reduction (target systolic BP, 140 mm Hg; n = 203) or standard guideline-based management of BP (target systolic BP, 180 mm Hg; n = 201) with intravenous agents. The mean interval from symptom onset to initiation of antihypertensive treatment was 4 hours in the intensive treatment group. The most commonly used agents were furosemide, urapidil (a calcium channel blocker), and phentolamine. The primary effi cacy end point was proportional change in ICH volume at 24 hours; secondary outcomes included other measurements of ICH volume change and standard safety and clinical outcome measures at 90 days. Results: Baseline characteristics of the two treatment arms were similar except that ICH volumes were slightly smaller in the guideline group (12.7 mL; SD, 11.6) than in the intensive treatment group (14.2 mL; SD, 14.5). From randomization to 1 hour, mean systolic BP was 153 mm Hg in the intensive treatment group and 167 mm Hg in the guideline group (mean difference, 13 mm Hg; P < 0.0001). From 1 to 24 hours, mean BP was 146 mm Hg in the intensive treatment group and 157 mm Hg in the guideline group (mean difference, 11 mm Hg; P < 0.0001). The mean proportional ICH volume growth at 24 hours was 36% in the guideline group and 14% in the intensive treatment group (absolute difference, 23%; P = 0.04). However, after adjustment for initial ICH volume and time from onset to CT, the difference in proportional ICH volume growth just missed statistical signifi cance (P = 0.06), and the absolute difference in change in ICH volume between groups was only 1.7 mL (95% CI, -0.5-3.9; P = 0.13). The relative risk of ICH volume growth ≥ 33% or ≥ 12.5 mL was 36% lower (95% CI, 0%-59%; P = 0.05) in the intensive treatment group than in the guideline group, and the absolute risk reduction was 8% (95% CI, -1%-17%; P = 0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days. Discussion: The authors concluded that early intensive BP-lowering treatment is clinically feasible, well tolerated, and may reduce hematoma growth in ICH. They indicated that a large randomized trial is needed to defi ne the effects on clinical outcomes across a broad range of patients with ICH.