ISC 2023 | LACI-2: cilostazol and isosorbide mononitrate for the treatment of lacunar stroke

Cilostazol and isosorbide mononitrate (ISMN) are two approved agents that have been highlighted for potential repurposing for the treatment of cerebral small vessel disease (SVD) and lacunar stroke. Cilostazol is a phosphodiesterase 3′ inhibitor used in stroke prevention and ISMN is a nitric oxide donor widely used in ischemic heart disease. Given the protective effects of these agents on the endothelium, the Lacunar Intervention Trials (LACI) set out to assess their safety and efficacy, alone and in combination, in patients with clinical lacunar ischemic stroke. LACI-1 found the medications to be well tolerated with short term use. LACI-2 expanded on these data, examining the effects of cilostazol and ISMN when given for 12 months. Joanna Wardlaw, CBE, MD, FRCP, FRSE, FMedSci, University of Edinburgh, Edinburgh, UK, and Philip Bath, DSc, FMedSci, The University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham, UK, discuss the findings of LACI-2 and how these results have informed the design of the planned Phase III LACI-3 trial. Over 360 patients were recruited, with high rates of retention at one year. With regards to safety, both agents demonstrated a strong safety profile, with very few cases of hemorrhage or death. ISMN use was shown to reduce recurrent stroke and cognitive impairment and improve quality of life, compared to no ISMN use. Cilostazol was shown to reduce dependency. Both agents trended towards reductions in the composite outcome of recurrent vascular events, cognitive impairment, dependency, and death. When used in combination, these effects were all protected or amplified, demonstrating proof-of-concept. This interview took place during the International Stroke Conference (ISC) 2023 in Dallas, TX.

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