Isosorbide Mononitrate, Cilostazol May Improve Lacunar Ischemic Stroke Outcomes

After lacunar ischemic stroke, patients treated with isosorbide mononitrate (ISMN) had reduced recurrent stroke and cognitive impairment, patients treated with cilostazol had reduced dependence, and patients treated with both drugs had a reduced composite outcome of vascular events, dependence, cognitive impairment, and death. Researchers published their findings online ahead of print in JAMA Neurology.

“These 2 inexpensive licensed medications (ISMN and cilostazol) may reduce adverse long-term outcomes of lacunar ischemic stroke, a form of cerebral small vessel disease, and definitive trials are needed to confirm these findings,” wrote corresponding author Joanna M. Wardlaw, MD, University of Edinburgh Centre for Clinical Brain Sciences in the United Kingdom, and study coauthors.

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The blinded end-point Lacunar Intervention Trial-2 study randomized 363 patients with lacunar ischemic stroke from numerous UK hospital stroke centers to either ISMN (40-60 mg/day), cilostazol (200 mg/day), ISMN-cilostazol (40-60 and 200 mg/day, respectively), or no study drug. All patients also received guideline stroke prevention treatment. The median time between stroke and randomization was 79 days.

At 1 year, 98.6% of patients were retained in the study, and 94.5% took at least 50% of their allotted drug, researchers reported. ISMN and cilostazol were well tolerated and safe.

Compared with patients not taking that particular medication, adjusted odds ratios were 0.23 for recurrent stroke and 0.55 for cognitive impairment at 12 months in patients taking ISMN. The adjusted odds ratio was 0.31 for dependence at 12 months in patients taking cilostazol, according to the study.

The 12-month adjusted odds ratio for a composite of vascular events, dependence, cognition, and death was 0.58 in patients taking combination ISMN and cilostazol. Meanwhile, adjusted odds ratios were 0.14 for dependence and 0.44 for any cognitive impairment, and the adjusted mean difference for improved quality of life was 0.10, with combination ISMN and cilostazol.

“These agents may reduce recurrent stroke, dependence, and cognitive impairment after lacunar stroke, and they could prevent other adverse outcomes in cerebral small vessel disease,” researchers wrote. “Therefore, both agents should be tested in large phase 3 trials.”

Reference

Wardlaw JM, Woodhouse LJ, Mhlanga II, et al. Isosorbide mononitrate and cilostazol treatment in patients with symptomatic cerebral small vessel disease: the Lacunar Intervention Trial-2 (LACI-2) randomized clinical trial. JAMA Neurol. Published online May 24, 2023. doi:10.1001/jamaneurol.2023.1526