Continuous Antihypertensive Therapy Throughout the Initial 24 Hours of Intracerebral Hemorrhage
The Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement–Intracerebral Hemorrhage Study
Background and Purpose—A short duration (<24 hours) of antihypertensive therapy (AHT) after acute intracerebral hemorrhage (ICH) may be sufficient because active bleeding generally ceases within several hours. We aimed to determine the association between sequential systolic blood pressure (SBP) levels during AHT and outcomes in ICH patients.
Methods—In 211 hyperacute ICH patients who underwent AHT based on predefined protocol, the mean of hourly SBP (mSBP) measurements was calculated over 1 to 8 hours (first mSBP), 9 to 16 hours (second mSBP), and 17 to 24 hours (third mSBP) after the initiation of AHT. Outcomes included neurological deterioration (72-hour Glasgow Coma Scale decrease ≥2 or National Instititutes of Health Stroke Scale increase ≥4), hematoma expansion (>33%), and unfavorable outcome (3-month modified Rankin Scale score 4–6).
Results—The median first, second, and third mSBPs were 132, 131, and 137 mm Hg, respectively. A higher first mSBP (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.34–4.69 per 10 mm Hg) or second mSBP (OR, 2.08; 95% CI, 1.20–3.80) was independently associated with neurological deterioration, and a higher second mSBP (OR, 1.40; 95% CI, 1.02–2.00) or third mSBP (OR, 1.45; 95% CI, 1.05–2.05) was associated with unfavorable outcome. None of the mSBPs was associated with hematoma expansion.
Conclusions—The continuation of AHT throughout the initial 24 hours after ICH may improve outcomes.
Blood pressure (BP) is often elevated after the onset of intracerebral hemorrhage (ICH). Elevated BP is associated with hematoma expansion,1 neurological deterioration,2 and unfavorable outcome.3,4 The recent results of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2) demonstrated that BP lowering may be beneficial for patients with hyperacute ICH.5 Although several trials, including the INTERACT2 and Antihypertensive Treatment of Acute Cerebral Hemorrhage II, required strict BP lowering during the initial ≥24 hours,5,6 the appropriate duration of antihypertensive therapy (AHT) in acute ICH is not clear. Hematoma expansion generally occurs within the initial several hours.7 Therefore, we hypothesized that AHT duration <24 hours may be sufficient to prevent hematoma expansion and improve clinical outcomes. We aimed to determine if the hourly systolic BP (SBP) levels during 1 to 8, 9 to 16, and 17 to 24 hours after the initiation of AHT are associated with different outcomes.
This study was a subanalysis of the Stroke Acute Management with Urgent Risk Factor Assessment and Improvement (SAMURAI)-ICH study, which was a prospective, multicenter, observational study. Details of SAMURAI-ICH were described previously.8,9 The predefined standardized protocol of AHT was used to lower and maintain SBP from 120 to 160 mm Hg during the initial 24 hours. BP was measured hourly for 24 hours, as well as at 48 and 72 hours. The hourly SBP measurements were averaged over 1 to 8 hours, 9 to 16 hours, and 17 to 24 hours after the initiation of AHT, and these values are referred to as the first, second, and third mean SBPs (mSBPs), respectively.
Outcomes included hematoma expansion (>33% in volume from baseline to 24 hours), neurological deterioration (a decrease ≥2 in Glasgow Coma Scale score or an increase ≥4 in National Instititutes of Health Stroke Scale score from baseline to 72 hours), and unfavorable outcome (modified Rankin Scale score 4–6 at 3 months). Multivariate logistic regression analysis was performed to determine the associations between the 3 different outcomes and each hourly SBP during the first 24 hours, SBPs at 48 and 72 hours, and first, second, and third mSBPs. The regression model was adjusted for known predictors of outcomes and interaction terms between the covariates of interest. Details of study methods are available in the online-only Data Supplement.
We enrolled 211 patients (81 women; median age, 65 [interquartile range, 58–74] years) in the SAMURAI-ICH study.8 The first, second, and third mSBPs [expressed as median (interquartile range)] were 132 (126–138), 131 (125–140), and 137 (130–144) mm Hg, respectively. Baseline characteristics are listed in Table I in the online-only Data Supplement. Briefly, hematoma expansion was observed in 36 patients (17%), neurological deterioration in 17 (8%), and unfavorable outcome in 87 (41%).
SBP course >24 hours was higher in those with neurological deterioration than in those without it (P trend=0.041), and there were no significant differences in SBP course over the entire 24 hours between those with and without hematoma expansion (P trend=0.568) and between those with and without unfavorable outcome (P trend=0.150; see Figure). However, SBP in the last 12 hours of AHT was lower in those without unfavorable outcome (P trend=0.027). The association between hourly SBP and outcomes demonstrated that neurological deterioration was significantly related to high SBP at 4, 8, 13, 15, and 17 hours, and unfavorable outcome was significantly related to high SBP at 4, 15, 19, and 22 hours (Figure I in the online-only Data Supplement). SBP levels at 48 and 72 hours were not significantly related to any outcome (data not shown).
The results of multivariable logistic regression analyses based on the 3 mSBP levels are presented in the online-only Data Supplement. There were no significant interaction terms between covariates from logistic regression models predicting outcomes. The first mSBP (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.34–4.69 per 10 mm Hg) and the second mSBP (OR, 2.08; 95% CI, 1.20–3.80) were independently associated with neurological deterioration. Furthermore, the second mSBP (OR, 1.40; 95% CI, 1.02–2.00) and the third mSBP (OR, 1.45; 95% CI, 1.05–2.05) were independently associated with unfavorable outcome, although none of the mSBPs was associated with hematoma expansion.
The first major finding of this study was that mSBPs during the first 16 hours of AHT were independently associated with neurological deterioration. The second major finding was that mSBPs during the last 16 hours of ATH were independently associated with unfavorable outcome. An additional important finding was that mSBP in the first, second, or third 8-hour period was not associated with hematoma expansion.
AHT has been performed during the initial ≥24 hours in recent successful trials, including INTERACT2.5 However, it may be practical to shorten the time period of AHT for strict BP control. Hematoma expansion is an important predictor of mortality and poor functional outcome after ICH1 and has been shown by pathological studies to occur within the initial several hours.10 A previous study at our institute based on CT showed that hematoma expansion was identified in 36% <3 hours of ICH onset, in 15% to 16% between 3 and 12 hours, in 6% between 12 and 24 hours, and in none after ≥24 hours.7 Thus, we hypothesized that SBP levels of the early hours (0–3), but not of the later hours (12–24), may affect chronic outcomes when AHT was given for the first 24 hours. Because the present results did not support this hypothesis, BP levels should be controlled throughout the first 24 hours after ICH onset.
Our results on the association between SBP and outcomes were unexpected with a lack of connection to hematoma expansion. INTERACT2 also demonstrated that intensive BP lowering did not reduce the rate of hematoma expansion or neurological deterioration, but tended to improve functional outcome.5 Perihematomal edema formation may be a potential mechanism to connect high BP levels during the later hours with poor outcomes.11 Another potential explanation for our results might be that 11% of our study patients were taking antithrombotic medications, and active bleeding in these patients might be prolonged. Therefore, a longer duration of AHT might be warranted.
In conclusion, the continuation of AHT during ≥24 hours after ICH onset may improve clinical outcomes in patients with hyperacute ICH.
We thank Kanae Takahashi, MPH, and Toshimitsu Hamasaki, MPH, for advice on statistical analyses.
Sources of Funding
This study was supported in part by a Grant-in-Aid (H20-Junkanki-Ippan-019 and H23-Junkanki-Ippan-010) from the Ministry of Health, Labour, and Welfare, Japan.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.113.004319/-/DC1.
- Received November 30, 2013.
- Accepted December 5, 2013.
- © 2014 American Heart Association, Inc.
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