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

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

Research output: Contribution to journalArticle

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Abstract

Background: Cilostazol and isosorbide mononitrate (ISMN) are candidate treatments for cerebral small vessel disease and lacunar ischaemic stroke. As both drugs may influence hemoglobin and platelet count, and hemodynamics, we sought to assess their effects in the lacunar intervention-1 (LACI-1) trial. Methods: Fifty-seven lacunar ischaemic stroke patients were randomized 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 hemodynamics (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 hemoglobin 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 randomized to cilostazol vs. no cilostazol and in those randomized 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 hemoglobin or platelet function over 8 weeks. Further assessment of the safety and efficacy of these medications following lacunar ischaemic stroke is warranted.

Original languageEnglish
Article number723
JournalFrontiers in Neurology
Volume10
Issue numberJUL
DOIs
Publication statusPublished - 1 Jan 2019

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isosorbide-5-mononitrate
Lacunar Stroke
Blood Platelets
Hemodynamics
Safety
Platelet Count
Heart Rate
Pharmaceutical Preparations
Vascular Stiffness
Hemoglobins
Cerebral Small Vessel Diseases
Blood Pressure
cilostazol

Keywords

  • Blood pressure
  • Cilostazol
  • Isosorbide mononitrate
  • Lacunar stroke
  • Platelets
  • Randomized clinical trial
  • Safety

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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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 P.; Blair, Gordon W.; Flaherty, Katie; Law, Zhe Kang; May, Jane; Woodhouse, Lisa J.; Doubal, Fergus; Sprigg, Nikola; Bath, Philip M.; Wardlaw, Joanna M.

In: Frontiers in Neurology, Vol. 10, No. JUL, 723, 01.01.2019.

Research output: Contribution to journalArticle

Appleton, Jason P. ; Blair, Gordon W. ; Flaherty, Katie ; Law, Zhe Kang ; May, Jane ; Woodhouse, Lisa J. ; Doubal, Fergus ; Sprigg, Nikola ; Bath, Philip M. ; Wardlaw, Joanna M. / 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. In: Frontiers in Neurology. 2019 ; Vol. 10, No. JUL.
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title = "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",
abstract = "Background: Cilostazol and isosorbide mononitrate (ISMN) are candidate treatments for cerebral small vessel disease and lacunar ischaemic stroke. As both drugs may influence hemoglobin and platelet count, and hemodynamics, we sought to assess their effects in the lacunar intervention-1 (LACI-1) trial. Methods: Fifty-seven lacunar ischaemic stroke patients were randomized 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 hemodynamics (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 hemoglobin 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 randomized to cilostazol vs. no cilostazol and in those randomized 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 hemoglobin or platelet function over 8 weeks. Further assessment of the safety and efficacy of these medications following lacunar ischaemic stroke is warranted.",
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T2 - Safety data from the Lacunar Intervention-1 (LACI-1) trial

AU - Appleton, Jason P.

AU - Blair, Gordon W.

AU - Flaherty, Katie

AU - Law, Zhe Kang

AU - May, Jane

AU - Woodhouse, Lisa J.

AU - Doubal, Fergus

AU - Sprigg, Nikola

AU - Bath, Philip M.

AU - Wardlaw, Joanna M.

PY - 2019/1/1

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N2 - Background: Cilostazol and isosorbide mononitrate (ISMN) are candidate treatments for cerebral small vessel disease and lacunar ischaemic stroke. As both drugs may influence hemoglobin and platelet count, and hemodynamics, we sought to assess their effects in the lacunar intervention-1 (LACI-1) trial. Methods: Fifty-seven lacunar ischaemic stroke patients were randomized 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 hemodynamics (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 hemoglobin 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 randomized to cilostazol vs. no cilostazol and in those randomized 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 hemoglobin or platelet function over 8 weeks. Further assessment of the safety and efficacy of these medications following lacunar ischaemic stroke is warranted.

AB - Background: Cilostazol and isosorbide mononitrate (ISMN) are candidate treatments for cerebral small vessel disease and lacunar ischaemic stroke. As both drugs may influence hemoglobin and platelet count, and hemodynamics, we sought to assess their effects in the lacunar intervention-1 (LACI-1) trial. Methods: Fifty-seven lacunar ischaemic stroke patients were randomized 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 hemodynamics (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 hemoglobin 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 randomized to cilostazol vs. no cilostazol and in those randomized 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 hemoglobin or platelet function over 8 weeks. Further assessment of the safety and efficacy of these medications following lacunar ischaemic stroke is warranted.

KW - Blood pressure

KW - Cilostazol

KW - Isosorbide mononitrate

KW - Lacunar stroke

KW - Platelets

KW - Randomized clinical trial

KW - Safety

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