Adding cilostazol to other antiplatelet agents could reduce post-CAS restenosis risk

Adding cilostazol to other antiplatelet agents could potentially reduce in-stent restenosis (ISR) among patients with carotid artery stenosis who undergo carotid artery stenting (CAS), according to results of the CAS-CARE* trial presented at ISC 2020.

The study population comprised 631 patients (mean age 69.8 years, 88.4 percent male) with symptomatic (≥50 percent stenosis) or asymptomatic (≥80 percent stenosis) carotid artery stenosis who were scheduled to undergo CAS within the next 30 days. They had been randomized to receive either cilostazol (100 or 200 mg BID; n=325) plus other antiplatelet agents or other antiplatelet agents only (n=306), initiated 3 days pre-CAS and continued for up to 2 years. A major proportion of patients assigned to the cilostazol group received concomitant antiplatelet agents (66.2, 60.3, and 6.4 percent also received aspirin, clopidogrel, and other antiplatelets, respectively).

Within 2 years post-CAS, ultrasound diagnosed ISR incidence (≥50 percent) was lower, though not statistically so, among patients who received cilostazol compared with those who received other antiplatelet agents (9.5 percent vs 15.0 percent; p=0.039; hazard ratio [HR], 0.64, 95 percent confidence interval [CI], 0.41–1.02; p=0.056). [ISC 2020, abstract LB21]

Landmark analysis showed that the benefit with cilostazol vs other agents only occurred beyond 30 days of treatment (10.3 percent vs 19.3 percent; HR, 0.62, 95 percent CI, 0.39–0.98; p=0.040), with no between-group difference in the first 30 days (0.6 percent vs 0.3 percent; HR, 1.89; p=0.598).

“[The researchers] did find that there was some benefit to adding cilostazol, and this is perhaps an exciting result with the degree of restenosis dropping from about 15 percent to about 9 percent or so. However, the results were not statistically significant,” noted Professor Mitchell Elkind from Columbia University New York City, New York, US, and president-elect of the American Heart Association, who was not affiliated with the study.

There was no significant difference between cilostazol and other antiplatelet agents in terms of a composite of CV events** or all-cause death (HR, 0.95, 95 percent CI, 0.51–1.80; p=0.886), or bleeding events (intracranial haemorrhage or systemic bleeding requiring transfusion; HR, 1.66, 95 percent CI, 0.48–5.66; p=0.416).

Severe ISR (≥70 percent) also occurred at a similar rate between those who received cilostazol or other antiplatelet agents (HR, 0.50; p=0.108), as did ischaemic (HR, 1.31; p=0.560) or haemorrhagic stroke (HR, 1.26; p=0.762). 

“This is the first trial to show potential effectiveness of medical management for the prevention of ISR after CAS,” said lead author Dr Hiroshi Yamagami from the National Hospital Organization Osaka National Hospital, Osaka, Japan.

However, he noted that the all-Japanese study population prevents the results from being extrapolated to other populations.

“[CAS] is being done frequently now for patients with both symptomatic and asymptomatic carotid stenosis, and it’s still not clear what the best way is to prevent the vessel from re-stenosing,” said Elkind. “These results may prompt further study in this area.”

While these findings are “a great thing to have available in the armamentarium,” they cannot be applied to routine use in patients with stents, he added.