Among high-risk hypertension patients with Cryptogenic Stroke, anticoagulation may be more effective than antiplatelet therapy: JAMA

A new study published in the Journal of the American Medical Association showed that in cryptogenic stroke, anticoagulation may be more effective than antiplatelet therapy in patients without high-risk hypertension features, while hypertension-related vascular disease may alter treatment response.

Cryptogenic stroke is a heterogeneous condition with varied underlying mechanisms. Hypertension risk stratification may help identify patients with cryptogenic stroke who are more likely to benefit from anticoagulation therapy. Unrecognized inclusion of hypertensive arteriopathy in prior trials may explain the lack of benefit observed with anticoagulation, which highlights the need for better patient selection and refined stroke classification in future studies.

For years, multiple trials have reported no clear advantage of anticoagulation over antiplatelet therapy in these patients, despite expectations that hidden cardiac causes might make blood thinners more effective. This research now look into the part of answer which may lie in hypertension-related cerebrovascular disease.

The data from ARCADIA trial focused on whether certain high-risk features of hypertension could influence how patients respond to treatment. The original trial enrolled over 1,000 patients across North America between 2018 and 2023, who underwent a recent cryptogenic stroke and showed signs of atrial cardiopathy.

In this follow-up study, 945 patients with complete data were analyzed. This research specifically looked for high-risk hypertension (systolic blood pressure of 160 mm Hg or higher), evidence of left ventricular hypertrophy on echocardiography, or both.

Among patients without high-risk hypertension, those treated with the anticoagulant apixaban had a significantly lower risk of recurrent stroke or systemic embolism when compared to those taking aspirin. In this group, apixaban reduced risk by more than half.

However, the benefit disappeared entirely in patients with high-risk hypertension. In fact, within this subgroup, apixaban showed no statistically significant advantage—and even trended toward worse outcomes compared to aspirin. Overall, 37% of participants met the criteria for high-risk hypertension, and across the study population, 67 recurrent events were recorded over a median follow-up of 1.6 years.

The results suggest that many patients previously labeled as having cryptogenic stroke may actually have strokes caused by hypertensive damage to small blood vessels in the brain. This misclassification could explain why earlier trials consistently failed to show superiority of blood thinners.

Overall, these findings point to more personalized treatment strategies, where blood pressure profiles and cardiac imaging help determine what type of therapy patients should receive.

Reference:

Ridha, M., Hailat, R., Stanton, R., Merkler, A. E., Elkind, M. S. V., Longstreth, W. T., Jr, Tirschwell, D. L., Kronmal, R. A., Hannawi, Y., Kamel, H., Burke, J., & Woo, D. (2026). Hypertension With High-Risk Features in Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Clinical Trial. JAMA Neurology, e260855. Advance online publication. https://doi.org/10.1001/jamaneurol.2026.0855