Isosorbide Mononitrate/Cilostazol for Lacunar Cerebral Small Vessel Disease-Outcomes at 6 Months in the LACI-2 Randomized Controlled Trial.
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.
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.
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]).
A reduction in the composite outcome, cognitive impairment, dependency, and stroke impact was seen within 6 months of starting ISMN or cilostazol.
URL: www.isrctn.com; Unique Identifier: ISRCTN14911850.
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.
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]).
A reduction in the composite outcome, cognitive impairment, dependency, and stroke impact was seen within 6 months of starting ISMN or cilostazol.
URL: www.isrctn.com; Unique Identifier: ISRCTN14911850.
Authors
Bath Bath, Woodhouse Woodhouse, Mhlanga Mhlanga, Bamford Bamford, Cvoro Cvoro, Doubal Doubal, England England, Hassan Hassan, Montgomery Montgomery, O'Brien O'Brien, Roffe Roffe, Sprigg Sprigg, Werring Werring, Wardlaw Wardlaw,
View on Pubmed