Key result
Early antihypertensive treatment fails to reduce death or disability in acute ischemic stroke regardless of genetic risk.
Why the study?
It remained unclear whether blood pressure genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke.
Does early antihypertensive treatment reduce the composite of death and major disability in patients with acute ischemic stroke across different blood pressure genetic variants?
RCT (n=2,590)
centrally stratified by participating hospitals and use of antihypertensive medications
Yes
Does early antihypertensive treatment reduce the composite of death and major disability in patients with acute ischemic stroke across different blood pressure genetic variants?
Effect estimate: OR 0.95, 1.08, and 0.91 (for low, intermediate, and high BP genetic risk scores) (95% CI 0.71-1.26, 0.80-1.44, 0.69-1.22)
p-value: p=0.88 for interaction
Blood pressure genetic variants do not modify the neutral effect of early antihypertensive treatment on clinical outcomes in patients with acute ischemic stroke.
Early antihypertensive treatment remains ineffective in acute ischemic stroke regardless of BP genetic risk; confirms neutral effect without genetic interaction.
BACKGROUND: It remains unclear whether blood pressure (BP) genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke. We conducted a secondary analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. METHODS: The CATIS randomized 4071 patients with acute ischemic stroke with elevated systolic BP to receive antihypertensive treatment or discontinue all antihypertensive agents during hospitalization. Randomization was conducted centrally and was stratified by participating hospitals and use of antihypertensive medications. Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. A weighted BP genetic risk score was constructed by the 5 single nucleotide polymorphisms. RESULTS: At 14 days or hospital discharge, the primary outcome was not significantly different between antihypertensive treatment and control groups based on genotype subgroups for all 5 single nucleotide polymorphisms (all P >0.05 for interaction). In addition, the BP genetic risk score did not modify the effect of antihypertensive treatment. The odds ratios (95% CIs) for the primary outcome were 0.95 (0.71–1.26), 1.08 (0.80–1.44), and 0.91 (0.69–1.22) in patients with low, intermediate, and high BP genetic risk score, respectively ( P =0.88 for interaction). CONCLUSIONS: Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01840072.
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Zhai et al. (2024) conducted an RCT in acute ischemic stroke with elevated systolic BP (n=2,590). immediate antihypertensive treatment vs. discontinue all antihypertensive agents was evaluated on combination of death and major disability at 14 days or hospital discharge (OR 0.95, 1.08, and 0.91 (for low, intermediate, and high BP genetic risk scores), 95% CI 0.71-1.26, 0.80-1.44, 0.69-1.22, p=0.88 for interaction). Early antihypertensive treatment did not significantly affect death and major disability at 14 days in acute ischemic stroke patients, regardless of BP genetic risk score (P=0.88 for interaction).
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