Stroke survivors taking a combination of the blood thinner cilostazol with aspirin or clopidogrel had a lower risk of ischaemic stroke recurrence than those who received aspirin or clopidogrel alone, according to late breaking science presented at the American Stroke Association's International Stroke Conference 2019.
Although aspirin and clopidogrel have been shown to reduce early recurrence of ischaemic stroke, the benefits seem to be short and was offset by a risk of major bleeding in long-term usage, said lead author Dr Kazunori Toyoda, deputy director general of the Hospital National Cerebral and Cardiovascular Centre in Suita, Osaka, Japan.
Since cilostazol has been shown to prevent stroke recurrence without increasing serious bleeding as compared to aspirin, researchers studied if dual antiplatelet therapy involving cilostazol would be safe and fit for long-term usage.
In a multicentre open-label, parallel-group trial, called The Cilostazol Stroke Prevention Study for Antiplatelet Combination, high-risk patients were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel at 292 sites in Japan over about four years. The study included 1,839 patients, including 756 taking aspirin and 1,083 taking clopidogrel. They had suffered an ischemic stroke up to six months earlier.
Researchers found that the risk of a recurrence of ischemic stroke in high-risk patients was less common with long-term dual medication with cilostazol plus aspirin or clopidogrel compared to long-term therapy with aspirin or clopidogrel alone and both approaches had a similar risk of major bleeding.
The study was funded by Otsuka Pharmaceutical.
Abstract
Background: Impairment of endothelial function is associated with atherosclerosis. Cilostazol is an antiplatelet drug that inhibits phosphodiesterase III, and has the potential to improve endothelial function. The prospective, open-label, randomized trial to evaluate the safety and efficacy of dual antiplatelet therapy involving cilostazol for secondary ischemic stroke prevention is ongoing (The Cilostazol Stroke Prevention Study for Antiplatelet Combination; CSPS.com) (Int J Stroke Vol 10, Feb 2015, 253).
Objective: The purpose of this study was to clarify the effect of cilostazol in addition to clopidogrel on endothelial function in patients with ischemic stroke.
Material and Methods: This study was a sub-study of CSPS.com, and registered in clinical trial (UMIN 000026672). The subjects were enrolled in our hospital from ischemic stroke patients taking clopidogrel after 8-180 days. They were randomly assigned into two groups, one with adding cilostazol on clopidogrel (CIL group), and other without cilostazol (Control group). Endothelial function was evaluated at enrollment and 6 months later, using the Flow Mediated Dilation (FMD) test of the brachial artery under blindness. Endothelial function was expressed as percent increase of brachial vessel diameter (%FMD) after interruption of blood flow with mechanical compression for five minutes. We also measured the plasma levels of inflammatory markers (highly sensitive C-reactive protein, interleukin 6, intercellular adhesion molecule-1, thrombomodulin) at enrollment and 6 months later. The ANOVA was used for statistical analysis.
Results: Total 29 subjects (Control group 16, CIL group 13) were enrolled. The mean age of subjects was 71.2±8.6 years old, and 81.3% were males. The baseline %FMD was similar between Control group (4.60±0.62%) and CIL group (4.68±0.69%). At 6 months, %FMD did not change in Control group, but %FMD significantly improved in CIL group (p<0.01). There was no significant change in plasma levels of any inflammatory markers in both groups.
Conclusion: This study showed that the %FMD significantly increased by adding cilostazol to clopidogrel in patients with ischemic stroke. Cilostazol may improve endothelial dysfunction independent of anti-inflammatory action.
Authors
Yuka Shirai, Sono Toi, Megumi Kubota, Eiko Higuchi, Masako Yamazaki, Utako Adachi, Kazuo Kitagawa
[link url="https://www.sciencedaily.com/releases/2019/02/190206200334.htm"]American Heart Association material[/link]
[link url="https://www.ahajournals.org/doi/10.1161/str.50.suppl_1.WP539"]Stroke abstract[/link]