{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:08:52Z","timestamp":1789013332697,"version":"build-2803163510"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Lacunar stroke can cause cognitive decline and dependency. The LACI\u20102 (Lacunar Intervention Trial\u20102) trial showed that 12\u2009months of treatment with isosorbide\u2010mononitrate (ISMN) or cilostazol improved these outcomes. We tested whether this effect was present at 6\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      LACI\u20102 was a prospective randomized open\u2010label blinded\u2010end point 2\u00d72\u2010factorial phase\u20102b trial assessing feasibility, safety, and proof\u2010of\u2010concept of 1\u2009year of ISMN (40\u201360\u2009mg) or cilostazol (200\u2009mg). Participants aged &gt;30\u2009years 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 &gt;2), cognitive impairment (\n                      <jats:italic toggle=\"no\">Diagnostic and Statistical Manual<\/jats:italic>\n                      version 5, 7\u2010level &gt;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\u2013Lachin test with result given as Mann\u2013Whitney difference.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Baseline characteristics were balanced across 363 participants: median age 64 (56\u201372) years, 31% female, and median onset to randomization 79 (27\u2013244) days. At 6\u2009months, participants allocated to ISMN versus control had fewer composite events (adjusted odds ratio [OR], 0.74 [95% CI, 0.55\u20130.99]) and improved stroke impact (Mann\u2013Whitney difference, \u22120.15 [95% CI \u22120.25 to \u22120.05]). Cilostazol versus control improved cognition (\n                      <jats:italic toggle=\"no\">Diagnostic and Statistical Manual<\/jats:italic>\n                      version 5, 7\u2010level scale, adjusted common OR, 0.64 [95% CI, 0.41\u20130.99]). ISMN\/cilostazol versus control improved cognition (\n                      <jats:italic toggle=\"no\">Diagnostic and Statistical Manual<\/jats:italic>\n                      version 5, 7\u2010level adjusted common OR, 0.40 [95% CI, 0.21\u20130.78]), mood (Zung adjusted mean difference, \u22126.94 [95% CI, \u221212.25 to \u22121.64]) and global stroke impact (Mann\u2013Whitney difference, \u22120.23 [95% CI, \u22120.37 to \u22120.09]).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">A reduction in the composite outcome, cognitive impairment, dependency, and stroke impact was seen within 6 months of starting ISMN or cilostazol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.isrctn.com\">www.isrctn.com<\/jats:ext-link>\n                      ; Unique Identifier: ISRCTN14911850.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046235","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:14:22Z","timestamp":1785496462000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Isosorbide Mononitrate\/Cilostazol for Lacunar Cerebral Small Vessel Disease\u2010Outcomes at 6\u2009Months in the LACI\u20102 Randomized Controlled Trial"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-5132","authenticated-orcid":false,"given":"Philip M.","family":"Bath","sequence":"first","affiliation":[{"name":"University of Nottingham","place":["UK"]},{"name":"Nottingham University Hospitals NHS Trust","place":["Nottingham, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-1999","authenticated-orcid":false,"given":"Lisa J.","family":"Woodhouse","sequence":"additional","affiliation":[{"name":"University of Nottingham","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-1630","authenticated-orcid":false,"given":"Iris","family":"Mhlanga","sequence":"additional","affiliation":[{"name":"University of Nottingham","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7817-8832","authenticated-orcid":false,"given":"John","family":"Bamford","sequence":"additional","affiliation":[{"name":"Leeds General Infirmary","place":["Leeds, 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Nottingham","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9716-8587","authenticated-orcid":false,"given":"Ahamad","family":"Hassan","sequence":"additional","affiliation":[{"name":"Leeds General Infirmary","place":["Leeds, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0450-1606","authenticated-orcid":false,"given":"Alan A.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"University of Nottingham","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"University of Cambridge School of Clinical Medicine","place":["Cambridge, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5259-6649","authenticated-orcid":false,"given":"Christine","family":"Roffe","sequence":"additional","affiliation":[{"name":"Keele University","place":["Stoke\u2010on\u2010Trent, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5871-8168","authenticated-orcid":false,"given":"Nikola","family":"Sprigg","sequence":"additional","affiliation":[{"name":"University of Nottingham","place":["UK"]},{"name":"Nottingham University Hospitals NHS Trust","place":["Nottingham, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2074-1861","authenticated-orcid":false,"given":"David J.","family":"Werring","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology","place":["London, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-6642","authenticated-orcid":false,"given":"Joanna M.","family":"Wardlaw","sequence":"additional","affiliation":[{"name":"University of 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