Early Antihypertensive Treatment may increase Death risk among Stroke Patients with PAD: CATIS-2 Trial Analysis

The findings published in JAMA Network Open underscore the need for a cautious approach to blood pressure (BP) management in these patients.

The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) indicates that early antihypertensive treatment does not reduce the risk of dependency or death in acute ischemic stroke (AIS) compared to delayed treatment. Given that single subcortical infarction is a significant subtype of stroke, the impact of the timing of antihypertensive therapy on clinical outcomes in these cases remains uncertain.

Against the above background, Yufei Wei, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and colleagues examine the relationship between early versus delayed antihypertensive treatment and clinical outcomes in patients with SSI, with a focus on whether the presence of PAD stenosis influences these outcomes.

This secondary analysis of the CATIS-2 randomized clinical trial involved 106 hospitals across China from June 2018 to July 2022. The trial included patients with AIS who presented within 24 to 48 hours of symptom onset and had elevated systolic blood pressure. For the current post hoc subgroup analysis, participants with SSI detected via diffusion-weighted imaging were examined. Patients were categorized into two groups: those with SSI and PAD stenosis, and those with SSI but without PAD stenosis. Statistical analysis for this study was conducted between July 2023 and May 2024.

The exposures of interest were early antihypertensive therapy (initiated immediately) versus delayed therapy (starting on day 8). The primary outcome measure was the combination of functional dependency or death, assessed by a modified Rankin Scale score of ≥3 at 90 days.

The study led to the following findings:

• Among 997 patients with SSI in CATIS-2 (mean age, 62.4 years; 61.4% men), 11.6% had SSI with PAD, and 88.4% had SSI without PAD.
• There was no significant difference in the primary outcome between early and delayed antihypertensive treatment groups among all patients with SSI (8.8% versus 7.1%; OR, 125).
• Among patients with SSI with PAD, early antihypertensive treatment was associated with increased risk of the primary outcome compared with delayed treatment (23.4% versus 7.7%; OR, 3.67); this finding was not observed in patients with SSI without PAD (6.6% versus 7.1%; OR, 0.93).
• Significant interaction with treatment and PAD stenosis presence was detected for the primary outcome.

The findings showed no overall association between early versus delayed antihypertensive treatment and clinical outcomes within three months for patients with acute single subcortical infarction. However, a significant interaction between treatment timing and the presence of parent artery disease stenosis was observed. Early antihypertensive treatment was linked to a higher risk of death or functional dependency at 90 days among patients with SSI who also had PAD stenosis, a relationship not seen in those without PAD stenosis.

"Further research is needed to investigate the mechanisms behind these findings and to develop more individualized blood pressure management strategies for patients with SSI," the researchers concluded.

Reference:

Wei Y, Xie X, Pan Y, et al. Early vs Delayed Antihypertensive Treatment in Acute Single Subcortical Infarction: A Secondary Analysis of the CATIS-2 Randomized Clinical Trial. JAMA Netw Open. 2024;7(8):e2430820. doi:10.1001/jamanetworkopen.2024.30820