Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease
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Le résumé fourni par la source
Importance: Cerebral small vessel disease (cSVD) is a common cause of stroke (lacunar stroke), is the most common cause of vascular cognitive impairment, and impairs mobility and mood but has no specific treatment. Objective: To test the feasibility, drug tolerability, safety, and effects of 1-year isosorbide mononitrate (ISMN) and cilostazol treatment on vascular, functional, and cognitive outcomes in patients with lacunar stroke. Design, Setting, and Participants: The Lacunar Intervention Trial-2 (LACI-2) was an investigator-initiated, open-label, blinded end-point, randomized clinical trial with a 2 × 2 factorial design. The trial aimed to recruit 400 participants from 26 UK hospital stroke centers between February 5, 2018, and May 31, 2021, with 12-month follow-up. Included participants had clinical lacunar ischemic stroke, were independent, were aged older than 30 years, had compatible brain imaging findings, had capacity to consent, and had no contraindications to (or indications for) the study drugs. Data analysis was performed on August 12, 2022. Interventions: All patients received guideline stroke prevention treatment and were randomized to ISMN (40-60 mg/d), cilostazol (200 mg/d), ISMN-cilostazol (40-60 and 200 mg/d, respectively), or no study drug. Main Outcomes: The primary outcome was recruitment feasibility, including retention at 12 months. Secondary outcomes were safety (death), efficacy (composite of vascular events, dependence, cognition, and death), drug adherence, tolerability, recurrent stroke, dependence, cognitive impairment, quality of life (QOL), and hemorrhage. Results: Of the 400 participants planned for this trial, 363 (90.8%) were recruited. Their median age was 64 (IQR, 56.0-72.0) years; 251 (69.1%) were men. The median time between stroke and randomization was 79 (IQR, 27.0-244.0) days. A total of 358 patients (98.6%) were retained in the study at 12 months, with 257 of 272 (94.5%) taking 50% or more of the allocated drug. Compared with those participants not receiving that particular drug, neither ISMN (adjusted hazard ratio [aHR], 0.80 [95% CI, 0.59 to 1.09]; P = .16) nor cilostazol (aHR, 0.77 [95% CI, 0.57 to 1.05]; P = .10) alone reduced the composite outcome in 297 patients. Isosorbide mononitrate reduced recurrent stroke in 353 patients (adjusted odds ratio [aOR], 0.23 [95% CI, 0.07 to 0.74]; P = .01) and cognitive impairment in 308 patients (aOR, 0.55 [95% CI, 0.36 to 0.86]; P = .008). Cilostazol reduced dependence in 320 patients (aHR, 0.31 [95% CI, 0.14 to 0.72]; P = .006). Combination ISMN-cilostazol reduced the composite (aHR, 0.58 [95% CI, 0.36 to 0.92]; P = .02), dependence (aOR, 0.14 [95% CI, 0.03 to 0.59]; P = .008), and any cognitive impairment (aOR, 0.44 [95% CI, 0.23 to 0.85]; P = .02) and improved QOL (adjusted mean difference, 0.10 [95% CI, 0.03 to 0.17]; P = .005) in 153 patients. There were no safety concerns. Conclusions and Relevance: These results show that the LACI-2 trial was feasible and ISMN and cilostazol were well tolerated and safe. These agents may reduce recurrent stroke, dependence, and cognitive impairment after lacunar stroke, and they could prevent other adverse outcomes in cSVD. Therefore, both agents should be tested in large phase 3 trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03451591.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease
- Date Crossref
- 01/07/2023
- Éditeur
- American Medical Association (AMA)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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UK Dementia Research Institute pays non établi dans la noticeStructure de recherche
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University of Edinburgh Centre for Clinical Brain Sciences pays non établi dans la noticeUniversité ou école supérieure
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University of Nottingham Mental Health and Clinical Neuroscience pays non établi dans la noticeUniversité ou école supérieure
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Leeds General Infirmary pays non établi dans la noticeÉtablissement de santé
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National Health Service pays non établi dans la noticeÉtablissement de santé
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Victoria Hospital pays non établi dans la noticeÉtablissement de santé
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University of Cambridge Department of Psychiatry pays non établi dans la noticeUniversité ou école supérieure
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Keele University Stroke Research pays non établi dans la noticeUniversité ou école supérieure
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National Hospital for Neurology and Neurosurgery pays non établi dans la noticeÉtablissement de santé
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University College London Stroke Research Centre pays non établi dans la noticeUniversité ou école supérieure
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Department of Neurology pays non établi dans la noticeInstitution
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for the Lacunar Intervention Trial-2 (LACI-2) Investigator Group pays non établi dans la noticeInstitution
UK Dementia Research Institute, Centre for Clinical Brain Sciences — University of Edinburgh et Mental Health and Clinical Neuroscience — University of Nottingham, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.