Isosorbide mononitrate / cilostazol for lacunar cerebral small vessel disease- outcomes at 6 months in the LACI-2 randomised controlled trial

BackgroundLacunar stroke can cause cognitive decline and dependency. The LACunar Intervention Trial-2 (LACI-2) trial showed that 12 months of treatment with isosorbide-mononitrate (ISMN) and/or cilostazol improved these outcomes. We tested whether this effect was present at 6 months.MethodsLACI-2 was a prospective randomised open-label blinded-endpoint 2x2-factorial phase-2b trial assessing feasibility, safety and proof-of-concept of one year of ISMN (40-60mg) and/or cilostazol (200 mg). Participants aged>30yrs 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>2), cognitive impairment (Diagnostic and Statistical Manual version 5-7-level, DSM5-7L>0) and death; key secondary outcomes included the composite components, mood and stroke impact scale. Global analysis of the stroke impact scale was analysed using the Wei-Lachin test with result given as Mann-Whitney difference (MWD).ResultsBaseline characteristics were balanced across 363 participants: median age 64 [56-72] years, females 31% and median onset-to-randomisation 79 [27-244] days. At 6 months, participants allocated to ISMN vs control had fewer composite events (adjusted odds-ratio, aOR 0.74, 95% confidence-intervals 0.55-0.99) and improved stroke impact (MWD -0.15, 95% CI -0.25, -0.05). Cilostazol vs control improved cognition (DSM5-7-level scale, acOR 0.64, 95% CI 0.41-0.99). ISMN/cilostazol vs control improved cognition (DSM5-7L acOR 0.40, 95% CI 0.21-0.78), mood (Zung aMD -6.94, 95% CI -12.25, -1.64) and global stroke impact (MWD -0.23, 95% CI -0.37, -0.09).ConclusionsA reduction in the composite outcome, cognitive impairment, dependency and stroke impact was seen within 6 months of starting ISMN and/or cilostazol.