04 Jul 19. Featured Paper
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.
Link to paper on Frontiers in Neurology
Jason P. Appleton, Gordon W. Blair, Katie Flaherty, Zhe Kang Law, Jane May, Lisa J. Woodhouse, Fergus Doubal, Nikola Sprigg, Philip M. Bath and Joanna M. Wardlaw
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.
Randomized clinical trial