Journal of the American Society of Hypertension 9(5) (2015) 331–333
Commentary
Should blood pressure be lowered in acute ischemic stroke? The CATIS trial Philip B. Gorelick, MD, MPHa,b,* a
Department of Translational Science and Molecular Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI; and b Hauenstein Neuroscience Center, Mercy Health, Grand Rapids, MI
In acute ischemic stroke (AIS), beyond few exceptions, the management of blood pressure (BP) remains uncertain.1–3 Past guidance has recommended that one may withhold antihypertensive agents in AIS unless diastolic BP is >120 mm Hg or systolic BP is >220 mm Hg or there is some other compelling reason to treat BP acutely (eg, intravenous tPA administration, acute myocardial infarction, aortic dissection, malignant hypertension).2,3 More recent American Heart Association/American Stroke Association (AHA/ASA) guidance recommends that it is reasonable to lower BP by 15% during the first 24 hours after stroke onset, noting also that patients may have a spontaneous decline of BP during the first 24 hours after stroke.1 On the one hand, it is argued that too aggressive BP–lowering in AIS may lead to extension of brain infarction in already threatened tissue of the ischemic penumbra, which may have poor autoregulatory capability. Also, too high a BP may potentiate leaky ischemic blood vessels to be more susceptible to mediating brain edema, hemorrhagic transformation, and neurologic worsening.2 Therefore, the clinician is caught in a position of clinical equipoise in relation to BP management in AIS. We now review the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) and select related studies to answer the question: should BP be lowered in AIS?
CATIS CATIS was a multicenter, randomized controlled trial designed to test whether moderate lowering of BP within the first 48 hours after onset of AIS could reduce death and major disability at 14 days or hospital discharge.4 Key elements of the study design are listed in the Table 1. CATIS patients were in their early 60s, randomized within about 15 hours from stroke onset, had entry BPs of w166.7/96.8 mm Hg, and National Institute of Health Stroke Scale scores suggesting mild impairment. CATIS emphasized acute BP reduction rather than a specific BP–lowering regimen. In CATIS, study BP targets were met. Within 24 hours, the active BP–lowering treatment group had mean systolic BP reduced by 12.7%, whereas that in the control group was reduced by 7.2%.4 At day 7, mean systolic BP was 137.3 mm Hg in the active treatment group and 146.5 mm Hg in the control group. However, the primary outcome of death and major disability did not differ between the comparative groups (683 vs. 681 events). Furthermore, the secondary outcome of death and major disability at 3 months did not significantly differ between the two comparator groups (500 vs. 502 events).
This manuscript was not supported by any outside funding or assistance with the writing of the manuscript. *Corresponding author: Dr Philip B. Gorelick, MD, MPH, Department of Translational Science and Molecular Medicine, Michigan State University College of Human Medicine, 220 Cherry St SE, Grand Rapids, MI 49503. Tel: 616-685-6455; Fax: 616-685-4351. E-mail: [email protected] 1933-1711/$ - see front matter Ó 2015 American Society of Hypertension. All rights reserved. http://dx.doi.org/10.1016/j.jash.2015.02.017
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P.B. Gorelick / Journal of the American Society of Hypertension 9(5) (2015) 331–333
Table 1 Key components of China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) trial design 1. 2. 3. 4. 5. 6.
Multicenter, single–blind, blinded endpoints, randomized trial 26 sites in China 4071 patients, 22 years of age and older, ischemic stroke confirmed by CT or MRI head, within 48 hours of symptom onset Systolic BP between 140 mm Hg and less than 220 mm Hg and diastolic BP up to 120 mm Hg Exclusions: severe heart failure, aortic dissection, cerebrovascular stenosis, resistant hypertension, intravenous tPA use, and deep coma BP–lowering goals: in the active treatment group, lower systolic BP by 10%–25% within the first 24 hours after randomization, and
Commentary
Should blood pressure be lowered in acute ischemic stroke? The CATIS trial Philip B. Gorelick, MD, MPHa,b,* a
Department of Translational Science and Molecular Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI; and b Hauenstein Neuroscience Center, Mercy Health, Grand Rapids, MI
In acute ischemic stroke (AIS), beyond few exceptions, the management of blood pressure (BP) remains uncertain.1–3 Past guidance has recommended that one may withhold antihypertensive agents in AIS unless diastolic BP is >120 mm Hg or systolic BP is >220 mm Hg or there is some other compelling reason to treat BP acutely (eg, intravenous tPA administration, acute myocardial infarction, aortic dissection, malignant hypertension).2,3 More recent American Heart Association/American Stroke Association (AHA/ASA) guidance recommends that it is reasonable to lower BP by 15% during the first 24 hours after stroke onset, noting also that patients may have a spontaneous decline of BP during the first 24 hours after stroke.1 On the one hand, it is argued that too aggressive BP–lowering in AIS may lead to extension of brain infarction in already threatened tissue of the ischemic penumbra, which may have poor autoregulatory capability. Also, too high a BP may potentiate leaky ischemic blood vessels to be more susceptible to mediating brain edema, hemorrhagic transformation, and neurologic worsening.2 Therefore, the clinician is caught in a position of clinical equipoise in relation to BP management in AIS. We now review the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) and select related studies to answer the question: should BP be lowered in AIS?
CATIS CATIS was a multicenter, randomized controlled trial designed to test whether moderate lowering of BP within the first 48 hours after onset of AIS could reduce death and major disability at 14 days or hospital discharge.4 Key elements of the study design are listed in the Table 1. CATIS patients were in their early 60s, randomized within about 15 hours from stroke onset, had entry BPs of w166.7/96.8 mm Hg, and National Institute of Health Stroke Scale scores suggesting mild impairment. CATIS emphasized acute BP reduction rather than a specific BP–lowering regimen. In CATIS, study BP targets were met. Within 24 hours, the active BP–lowering treatment group had mean systolic BP reduced by 12.7%, whereas that in the control group was reduced by 7.2%.4 At day 7, mean systolic BP was 137.3 mm Hg in the active treatment group and 146.5 mm Hg in the control group. However, the primary outcome of death and major disability did not differ between the comparative groups (683 vs. 681 events). Furthermore, the secondary outcome of death and major disability at 3 months did not significantly differ between the two comparator groups (500 vs. 502 events).
This manuscript was not supported by any outside funding or assistance with the writing of the manuscript. *Corresponding author: Dr Philip B. Gorelick, MD, MPH, Department of Translational Science and Molecular Medicine, Michigan State University College of Human Medicine, 220 Cherry St SE, Grand Rapids, MI 49503. Tel: 616-685-6455; Fax: 616-685-4351. E-mail: [email protected] 1933-1711/$ - see front matter Ó 2015 American Society of Hypertension. All rights reserved. http://dx.doi.org/10.1016/j.jash.2015.02.017
332
P.B. Gorelick / Journal of the American Society of Hypertension 9(5) (2015) 331–333
Table 1 Key components of China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) trial design 1. 2. 3. 4. 5. 6.
Multicenter, single–blind, blinded endpoints, randomized trial 26 sites in China 4071 patients, 22 years of age and older, ischemic stroke confirmed by CT or MRI head, within 48 hours of symptom onset Systolic BP between 140 mm Hg and less than 220 mm Hg and diastolic BP up to 120 mm Hg Exclusions: severe heart failure, aortic dissection, cerebrovascular stenosis, resistant hypertension, intravenous tPA use, and deep coma BP–lowering goals: in the active treatment group, lower systolic BP by 10%–25% within the first 24 hours after randomization, and
