Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease

• DOI: 10.1001/jamaneurol.2023.1526
• Publication Date: 2023-05-24T10:30:37Z
• Authors: Joanna M. Wardlaw; Lisa J. Woodhouse; Iris I. Mhlanga; Katherine Oatey; Anna K. Heye; John Bamford; Vera Cvoro; Fergus N. Doubal; Timothy England; Ahamad Hassan; Alan Montgomery; John T. O’Brien; Christine Roffe; Nikola Sprigg; David J. Werring; Philip M. Bath; ; Colin Baigent; Gary Ford; Jonathan Emberson; Alison Murray; A Ross Naylor; Kailash Krishnan; Jesse Dawson; Chris Patterson; German Guzman Gut...; Stephen Makin; Usman Khan; Laszlo Sztriha; Thomas Booth; Amanathan Kirthiv...; Anwar Ijaz; Kirsty Harkness; Sevasti Ispoglou; Nigel Smyth; Aravinth Sivagnan...; David Cohen; Lakshmanan Sekaran; Dinesh Chadha; Nasar Ahmad; Pratap Rana; Malik Hussain; Nic Weir; Thomas Harrison; Salim Elyas
• Keywords: Cilostazol; Tolerability; Lacunar stroke; Stroke; Isosorbide mononitrate

Importance Cerebral small vessel disease (cSVD) is a common cause of stroke (lacunar stroke), the most vascular cognitive impairment, and impairs mobility mood but has no specific treatment. Objective To test feasibility, drug tolerability, safety, effects 1-year isosorbide mononitrate (ISMN) cilostazol treatment on vascular, functional, outcomes in patients with lacunar stroke. Design, Setting, Participants The Lacunar Intervention Trial-2 (LACI-2) was an investigator-initiated, open-label, blinded end-point, randomized clinical trial 2 × factorial design. aimed to recruit 400 participants from 26 UK hospital centers between February 5, 2018, May 31, 2021, 12-month follow-up. Included had ischemic stroke, were independent, aged older than 30 years, compatible brain imaging findings, capacity consent, contraindications (or indications for) study drugs. Data analysis performed August 12, 2022. Interventions All received guideline prevention ISMN (40-60 mg/d), (200 ISMN-cilostazol 200 mg/d, respectively), or drug. Main Outcomes primary outcome recruitment including retention at 12 months. Secondary safety (death), efficacy (composite events, dependence, cognition, death), adherence, recurrent quality life (QOL), hemorrhage. Results Of planned for this trial, 363 (90.8%) recruited. Their median age 64 (IQR, 56.0-72.0) years; 251 (69.1%) men. time randomization 79 27.0-244.0) days. A total 358 (98.6%) retained months, 257 272 (94.5%) taking 50% more allocated Compared those not receiving that particular drug, neither (adjusted hazard ratio [aHR], 0.80 [95% CI, 0.59 1.09]; P = .16) nor (aHR, 0.77 0.57 1.05]; .10) alone reduced composite 297 patients. Isosorbide 353 odds [aOR], 0.23 0.07 0.74]; .01) impairment 308 (aOR, 0.55 0.36 0.86]; .008). Cilostazol dependence 320 0.31 0.14 0.72]; .006). Combination 0.58 0.92]; .02), 0.03 0.59]; .008), any 0.44 0.85]; .02) improved QOL mean difference, 0.10 0.17]; .005) 153 There concerns. Conclusions Relevance These results show LACI-2 feasible well tolerated safe. agents may reduce after they could prevent other adverse cSVD. Therefore, both should be tested large phase 3 trials. Trial Registration ClinicalTrials.gov Identifier: NCT03451591