Effects of Blood Pressure and Lowering in First 24 Hours of Stroke
What are the short- and long-term effects of blood pressure and blood pressure lowering in the first 24 hours of ischemic stroke?
This was an exploratory, post-hoc analysis of patients enrolled in the IST-3 (Third International Stroke Trial). This trial randomized 3,035 patients to intravenous tissue-type plasminogen activator (t-PA) versus open control in the first 6 hours after stroke. The trial, conducted primarily in Europe, enrolled patients who did not meet t-PA licensing criteria at the time. Most of the patients in the trial were older (median age 81 years) with moderate-severe strokes (median National Institutes of Health Stroke Scale [NIHSS] score 11). To be eligible for the trial, the patients had to have blood pressures <220/130 mm Hg. Blood pressure measurement was done according to local protocols and recorded at: randomization; the start of treatment (or immediately after randomization in the control group); and at the following time points after randomization: 30 minutes, 1 hour, and 24 hours. Only systolic blood pressure was used in these analyses. Blood pressure treatments were recorded, but there was no standardization of antihypertensive type or protocol for use in the trial. Blood pressure variability was defined as the standard deviation (SD) of systolic blood pressure measurements. Endpoints included: symptomatic cerebral edema, symptomatic intracerebral hemorrhage (sICH), neurologic deterioration, death, and functional outcome at 6 months. The associations between blood pressure variables and endpoints were tested with logistic regression with adjustments for age, NIHSS, time to randomization, and allocated treatment (t-PA vs. control). When the relationship between blood pressure variability or blood pressure treatments and endpoints was examined, the authors adjusted for systolic blood pressure at randomization.
The majority of the 3,035 patients in the trial (>95%) were included in the analyses. Systolic blood pressures were similar between patients allocated to t-PA and control. After randomization, blood pressure was lower at 24 hours in the t-PA group than the control group (mean 15.9 mm Hg vs. 12.4 mm Hg lower than baseline). Patients who had any adverse event in the first 7 days after stroke had a higher blood pressure than patients without an adverse event (mean 162 mm Hg vs. 159 mm Hg; p = 0.016). When specific events were evaluated, the only event with statistical significance was sICH (p = 0.015). Greater blood pressure variability was associated with any adverse event in the first 7 days after stroke (mean blood pressure SD 14.7 vs. 13.4; p = 0.003). When specific events were evaluated with blood pressure variability, death was the only specific event with statistical significance (p = 0.001). Patients with a larger decline in blood pressure at 24 hours had a lower risk of sICH (p = 0.037) and a lower risk of poor functional outcome at 6 months (p = 0.001). Antihypertensive treatment was administered to 35.6% of patients in the t-PA group and 38.3% of patients in the control group. Receiving blood pressure lowering treatment was associated with a reduced risk of poor functional outcome at 6 months (59.6% vs. 66.8%; p = 0.007).
Elevated systolic blood pressure and increased systolic blood pressure variability are associated with an increased risk of early adverse events and poor functional outcome at 6 months after ischemic stroke.
This study provides additional data regarding the association between high blood pressure and poor outcome in acute ischemic stroke. While blood pressure variability has been shown to be a risk for ischemic stroke and is associated with worse outcomes acutely in ICH, this is the largest study to show that blood pressure variability in the first day after ischemic stroke is associated with an increased risk of adverse events. These data also support the hypothesis that actively lowering blood pressure in acute ischemic stroke has the potential to improve outcomes. Despite these findings, data from this study should be interpreted with caution. This was an observational study of a group of patients enrolled in a clinical trial, so confounding and bias may be playing a role in the results. In addition, blood pressure may be a marker of poor prognosis instead of the cause, which limits the applicability of these results. These data provide support to ongoing studies of blood pressure management in acute ischemic stroke that will help to determine the optimal blood pressure parameters in the first hours of treatment.
Keywords: Blood Pressure, Antihypertensive Agents, Brain Edema, Cerebral Hemorrhage, Cerebral Infarction, Fibrinolytic Agents, Hypertension, Risk, Stroke, Thrombolytic Therapy, Tissue Plasminogen Activator
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