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Effects of Isosorbide Mononitrate and/or Cilostazol on Hematological Markers, Platelet Function, and Hemodynamics in Patients With Lacunar Ischaemic Stroke: Safety Data From the Lacunar Intervention-1 (LACI-1) Trial

Appleton, Jason; Blair, Gordon W.; Flaherty, Katie; Law, Zhe; May, Jane; Woodhouse, Lisa J.; Doubal, Fergus; Sprigg, Nikola; Bath, Philip M.; Wardlow, Joanna M.

Authors

Jason Appleton

Gordon W. Blair

Katie Flaherty

Zhe Law

Jane May

Lisa J. Woodhouse

Fergus Doubal

Nikola Sprigg

Philip M. Bath

Joanna M. Wardlow



Abstract

Background
Cilostazol and isosorbide mononitrate (ISMN) are candidate treatments for cerebral small vessel disease and lacunar ischaemic stroke. As both drugs may influence haemoglobin and platelet count, and haemodynamics, we sought to assess their effects in the lacunar intervention-1 (LACI-1) trial.

Methods
57 lacunar ischaemic stroke patients were randomised to immediate ISMN, cilostazol, or their combination for 9 weeks in addition to guideline stroke prevention. A fourth group received both drugs with a delayed start. Full blood count, platelet function, peripheral blood pressure (BP), heart rate and central haemodynamics (Augmentation index, Buckberg index) were measured at baseline, and weeks 3 and 8. Differences were assessed by multiple linear regression adjusted for baseline and key prognostic variables. Registration ISRCTN 12580546.

Results
At week 8, platelet count was higher with cilostazol vs. no cilostazol (mean difference, MD 35.73, 95% confidence intervals, 95% CI 2.81-68.66, p=0.033), but no significant differences were noted for haemoglobin levels or platelet function. At week 8, BP did not differ between the treatment groups, whilst heart rate was higher in those taking cilostazol vs. no cilostazol (MD 6.42, 95% CI 1.17-11.68, p=0.017). Buckberg index (subendocardial perfusion) was lower in those randomised to cilostazol vs. no cilostazol and in those randomised to both drugs vs. either drug. Whilst ISMN significantly increased unadjusted augmentation index (arterial stiffness, MD 21.19, 95% CI 9.08-33.31, p=0.001), in isolation both drugs non-significantly reduced augmentation index adjusted for heart rate.

Conclusions
Cilostazol increased heart rate and platelet count, and reduced Buckberg index, whilst both drugs may individually reduce arterial stiffness adjusted for heart rate. Neither drug had clinically significant effects on haemoglobin or platelet function over 8 weeks. Further assessment of the safety and efficacy of these medications following lacunar ischaemic stroke is warranted.

Journal Article Type Article
Publication Date Jul 3, 2019
Journal Frontiers in Neurology
Electronic ISSN 1664-2295
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 10
Article Number 723
Pages 1-6
APA6 Citation Appleton, J., Blair, G. W., Flaherty, K., Law, Z., May, J., Woodhouse, L. J., …Wardlow, J. M. (2019). Effects of Isosorbide Mononitrate and/or Cilostazol on Hematological Markers, Platelet Function, and Hemodynamics in Patients With Lacunar Ischaemic Stroke: Safety Data From the Lacunar Intervention-1 (LACI-1) Trial. Frontiers in Neurology, 10, 1-6. https://doi.org/10.3389/fneur.2019.00723
DOI https://doi.org/10.3389/fneur.2019.00723
Keywords cilostazol, isosorbide mononitrate, blood pressure, safety, platelets, lacunar stroke, randomised clinical trial
Publisher URL https://www.frontiersin.org/articles/10.3389/fneur.2019.00723/full

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Effects of Isosorbide Mononitrate and/or Cilostazol on Hematological Markers, Platelet Function, and Hemodynamics in Patients With Lacunar Ischaemic Stroke: Safety Data From the Lacunar Intervention-1 (LACI-1) Trial (405 Kb)
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