Isosorbide Mononitrate/Cilostazol for Lacunar Cerebral Small Vessel Disease-Outcomes at 6 Months in the LACI-2 Randomized Controlled Trial.

BACKGROUND

Lacunar stroke can cause cognitive decline and dependency. The LACI-2 (Lacunar Intervention Trial-2) trial showed that 12 months of treatment with isosorbide-mononitrate (ISMN) or cilostazol improved these outcomes. We tested whether this effect was present at 6 months.

METHODS

LACI-2 was a prospective randomized open-label blinded-end point 2×2-factorial phase-2b trial assessing feasibility, safety, and proof-of-concept of 1 year of ISMN (40-60 mg) or cilostazol (200 mg). Participants aged >30 years had clinical lacunar stroke, compatible neuroimaging, and capacity to consent. The primary clinical outcome was the composite of stroke, myocardial infarction, dependency (modified Rankin Scale score >2), cognitive impairment (Diagnostic and Statistical Manual version 5, 7-level >0) and death; key secondary outcomes included the composite components, mood and stroke impact scale. Global analysis of the stroke impact scale was analyzed using the Wei-Lachin test with result given as Mann-Whitney difference.

RESULTS

Baseline characteristics were balanced across 363 participants: median age 64 (56-72) years, 31% female, and median onset to randomization 79 (27-244) days. At 6 months, participants allocated to ISMN versus control had fewer composite events (adjusted odds ratio [OR], 0.74 [95% CI, 0.55-0.99]) and improved stroke impact (Mann-Whitney difference, -0.15 [95% CI -0.25 to -0.05]). Cilostazol versus control improved cognition (Diagnostic and Statistical Manual version 5, 7-level scale, adjusted common OR, 0.64 [95% CI, 0.41-0.99]). ISMN/cilostazol versus control improved cognition (Diagnostic and Statistical Manual version 5, 7-level adjusted common OR, 0.40 [95% CI, 0.21-0.78]), mood (Zung adjusted mean difference, -6.94 [95% CI, -12.25 to -1.64]) and global stroke impact (Mann-Whitney difference, -0.23 [95% CI, -0.37 to -0.09]).

CONCLUSIONS

A reduction in the composite outcome, cognitive impairment, dependency, and stroke impact was seen within 6 months of starting ISMN or cilostazol.

REGISTRATION: URL: www.isrctn.com; Unique Identifier: ISRCTN14911850.