TY - JOUR
T1 - Interaction of blood pressure lowering and alteplase dose in acute ischemic stroke
T2 - results of the Enhanced Control of Hypertension and Thrombolysis Stroke Study
AU - Wang, Xia
AU - Song, Lili
AU - Yang, Jie
AU - Sun, Lingli
AU - Moullaali, Tom J.
AU - Sandset, Else Charlotte
AU - Delcourt, Candice
AU - Lindley, Richard I.
AU - Robinson, Thompson G.
AU - Minhas, Jatinder S.
AU - Arima, Hisatomi
AU - Chalmers, John
AU - Kim, Jong S.
AU - Sharma, Vijay
AU - Wang, Ji-Guang
AU - Pontes-Neto, Octavio
AU - Lavados, Pablo M.
AU - Olavarría, Veronica V.
AU - Lee, Tsong-Hai
AU - Levi, Christopher
AU - Martins, Sheila O.
AU - Thang, Nguyen H.
AU - Anderson, Craig S.
AU - ENCHANTED Investigators
PY - 2019/12/6
Y1 - 2019/12/6
N2 - Objective: To determine the extent to which the effects of intensive blood pressure (BP) lowering are modified by doses of alteplase in thrombolysis-eligible acute ischemic stroke (AIS) patients.Methods: Prespecified analyses of the Enhanced Control of Hypertension and Thrombolysis Stroke Study for patients enrolled in both arms: (i) low-dose (0.6 mg/kg body weight) or standard-dose (0.9 mg/kg) alteplase and (ii) intensive (target systolic BP [SBP] 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP management. The primary outcome was functional recovery, measured by a shift in scores on modified Rankin scale at 90 days. The safety outcome was any intracranial hemorrhage (ICH).Results: There were 925 participants (mean age 67 years, 39% female, 77% Asian) randomized to both arms: 242 randomly assigned to guideline/standard-dose (GS); 234 to guideline/low-dose (GL); 227 to intensive/standard-dose (IS); and 222 to intensive/low-dose (IL). Overall, average SBP levels within 24 h were lower in the low-dose compared to standard-dose alteplase group (146 and 144 vs. 151 and 150 mm Hg, for GS and GL vs. IS and IL, respectively, p < 0.0001). There was no heterogeneity of the effects of BP lowering (intensive vs. guideline) on functional recovery between standard-dose (OR 0.81, 95% CI 0.59-1.12) and low-dose alteplase (1.06, 0.77-1.47; p = 0.25 for interaction). Similar results were observed for ICH (p = 0.50 for interaction).Conclusions: In thrombolysis-treated patients with predominantly mild-to-moderate severity AIS, intensive BP lowering neither improve functional recovery, either with low- or standard-dose intravenous alteplase, nor beneficially interact with low-dose alteplase in reducing ICH.Trial Registration: The trial is registered with ClinicalTrials.gov (NCT01422616).
AB - Objective: To determine the extent to which the effects of intensive blood pressure (BP) lowering are modified by doses of alteplase in thrombolysis-eligible acute ischemic stroke (AIS) patients.Methods: Prespecified analyses of the Enhanced Control of Hypertension and Thrombolysis Stroke Study for patients enrolled in both arms: (i) low-dose (0.6 mg/kg body weight) or standard-dose (0.9 mg/kg) alteplase and (ii) intensive (target systolic BP [SBP] 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP management. The primary outcome was functional recovery, measured by a shift in scores on modified Rankin scale at 90 days. The safety outcome was any intracranial hemorrhage (ICH).Results: There were 925 participants (mean age 67 years, 39% female, 77% Asian) randomized to both arms: 242 randomly assigned to guideline/standard-dose (GS); 234 to guideline/low-dose (GL); 227 to intensive/standard-dose (IS); and 222 to intensive/low-dose (IL). Overall, average SBP levels within 24 h were lower in the low-dose compared to standard-dose alteplase group (146 and 144 vs. 151 and 150 mm Hg, for GS and GL vs. IS and IL, respectively, p < 0.0001). There was no heterogeneity of the effects of BP lowering (intensive vs. guideline) on functional recovery between standard-dose (OR 0.81, 95% CI 0.59-1.12) and low-dose alteplase (1.06, 0.77-1.47; p = 0.25 for interaction). Similar results were observed for ICH (p = 0.50 for interaction).Conclusions: In thrombolysis-treated patients with predominantly mild-to-moderate severity AIS, intensive BP lowering neither improve functional recovery, either with low- or standard-dose intravenous alteplase, nor beneficially interact with low-dose alteplase in reducing ICH.Trial Registration: The trial is registered with ClinicalTrials.gov (NCT01422616).
KW - Acute ischemic stroke
KW - Blood pressure lowering
KW - Hypertension
KW - Intracerebral hemorrhage
KW - Thrombolysis
UR - http://www.scopus.com/inward/record.url?scp=85076685776&partnerID=8YFLogxK
U2 - 10.1159/000504745
DO - 10.1159/000504745
M3 - Article
C2 - 31812956
SN - 1015-9770
VL - 48
SP - 207
EP - 216
JO - Cerebrovascular Diseases
JF - Cerebrovascular Diseases
IS - 3-6
ER -