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Comment & Response
March 15, 2021

Insights on Intensive Vs Nonintensive Prerandomization Systolic Blood Pressure Reduction—Reply

Author Affiliations
  • 1Zeenat Qureshi Stroke Institute, University of Missouri, Columbia
  • 2Department of Neurology, University of Missouri, Columbia
JAMA Neurol. 2021;78(5):620. doi:10.1001/jamaneurol.2021.0261

In Reply We thank Mahabala et al for their letter. We performed the analysis using postrandomization treatment groups based on systolic blood pressure (SBP) target values (intensive-arm goal, 110-139 mm Hg; standard-arm goal, 140-179 mm Hg).1 The first SBP level recorded in the emergency department was termed the initial SBP. The protocol permitted initiation of antihypertensive treatment (often by intravenous nicardipine infusion) before randomization to lower the SBP level to less than 180 mm Hg,2 which was consistent with the contemporary American Stroke Association Stroke Council guidelines,3 but the SBP level was to be maintained at 140 mm Hg or more before randomization. The initiation of antihypertensive treatment before randomization resulted in prerandomization SBP level reduction in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. The issue regarding prerandomization or ultra-early intensive reduction of SBP being more beneficial than intensive SBP reduction at later points has been raised previously.4 Mahabala et al have provided a valuable analysis of the data supporting the hypothesis in their letter. Li et al4 also reported that among 354 patients in whom intravenous nicardipine treatment was initiated within 2 hours, the frequency of hematoma expansion was significantly lower in the intensive blood pressure reduction group compared with the standard treatment group. Multivariable analysis showed that ultra-early intensive blood pressure treatment was associated with a decreased risk of hematoma expansion, a higher rate of functional independence, and good outcome at 90 days. One issue to be cautious about in prerandomization SBP reduction is that the SBP reduction groups are created based on post hoc conceptualization. Therefore, the limitations of post hoc analysis apply and should be taken into account during interpretation.

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