Cilostazol: An Option for Ischemic Stroke After ICH?

March 02, 2017

HOUSTON, Texas — The antiplatelet agent cilostazol was noninferior to aspirin in preventing vascular events in patients with a recent ischemic stroke and a history of intracerebral hemorrhage (ICH) or multiple microbleeds in the PICASSO trial.

Cilostazol also showed a strong trend toward less cerebral bleeding, but this finding did not reach statistical significance.

In terms of vascular events, cilostazol appeared more effective than aspirin at reducing recurrent ischemic strokes but less effective at preventing myocardial infarction (MI).

Presenting the data here at the International Stroke Conference (ISC) 2017, Sun U. Kwon Sr, MD, Asan Medical Center, Seoul, Korea, concluded that "cilostazol could be considered for secondary stroke prevention in ischemic stroke patients prone to cerebral hemorrhage but it may need consideration for MI risk."

Dr Sun U. Kwon Sr

Commenting on the results, Amytis Towfighi, MD, director, Neurological Services and Innovation, Los Angeles County Department of Health Services, California, called this an "important study."

Because hypertension causes both ischemic and hemorrhagic stroke, patients at risk for ischemic stroke are also at risk for hemorrhagic stroke. And those who have already had a previous cerebral bleed when they have an ischemic stroke are notoriously difficult to treat.

American Heart Association/American Stroke Association spokesperson, Mark J. Alberts, MD, chief of neurology at Hartford Hospital and head of the Hartford Healthcare Neuroscience Institute in Connecticut, explained that cilostazol has been available for many years and is popular in Asian countries. He added: "It is believed to be a safer option than aspirin or clopidogrel in terms of bleeding, and Asians have a greater risk of ICH than Caucasians. In the West it is typically used for peripheral vascular disease."

Regarding the PICASSO results, Dr Alberts said, "This is a well-done study, but I don't see the results changing practice in the US at this time."

Commenting for Medscape Medical News, Philip Bath, FRCP, DSc, University of Nottingham, United Kingdom, agreed that the PICASSO results would not be enough to recommend use of cilostazol in this situation in the West. "The drug is a bit of an unknown here and not well accepted. We need to understand it better," he noted.

"The PICASSO study was a relatively small trial and limited to the Asian population, but it has shown very interesting and appealing results, and I think we need to take notice of this study," he added. "I would like to see another similar trial conducted in the West."

Dr Bath stressed the difficulty of treating this patient group. "Patients who have had a previous cerebral bleed before are at a high risk of having another one, so using an antiplatelet drug is questionable. But if they have suffered a recent ischemic stroke then they are also at risk of having another one of these, so they also need protection from that. We just treat each case individually at present, trying to balance risk and benefits — we normally treat the most recent event, but it is an extremely problematic area."

The PICASSO trial involved 1512 patients from Korea, Hong Kong, and the Philippines who had had a noncardioembolic ischemic stroke or transient ischemic attack within the last 180 days and who had also had a previous ICH based on clinical or radiologic findings or multiple cerebral microbleeds (not within the last 6 months).

Patients were randomly assigned to cilostazol (200 mg/day) or aspirin (100 mg/day) for ongoing treatment.

The trial evaluated efficacy (stroke, MI, and vascular death) with a noninferiority analysis and evaluated safety (hemorrhagic stroke) with a superiority analysis.

Results showed that after a mean follow-up of 2 years, cilostazol was found to be noninferior to aspirin for the primary efficacy endpoint, and although there was a strong trend toward fewer cerebral hemorrhages in the cilostazol group, the superiority criteria for the safety endpoint were not met.

Table. PICASSO: Main Results

Endpoint Cilostazol: No. of Events Cilostazol: Incidence (per 100 Person-Years) Aspirin: No. of Events Aspirin: Incidence (per 100 Person-Years) Hazard Ratio (95% Confidence Interval) P Value
Composite of cardiovascular events 63 4.27 80 5.33 0.80 (0.60 - 1.05) .004
Cerebral hemorrhage 9 0.61 18 1.20 0.51 (0.23 - 1.13) .09

 

Stroke occurred less frequently in the cilostazol group (48 events, 3.25/100 person-years) than in the aspirin group (73 events, 4.86/100 person-years; P = .0273).

However, MI occurred more in the cilostazol group (9 events, 0.61/100 person-years) than in the aspirin group (2 events, 0.13/100 person-years; P = .0319).

The investigator-initiated PICASSO trial was funded by Korea Otsuka Pharmaceutical Company. Dr Kwon reports funded research and honoraria/expense in the last 5 years from Bayer, Boehringer Ingelheim, Otsuka, Pfizer, and Boryung.

International Stroke Conference (ISC) 2017. Abstract LB5. Presented February 23, 2017.

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