Ticagrelor for Stroke: Encouraging Results in Platelet Study

February 23, 2018

The use of ticagrelor (Brilinta, Astra Zeneca) plus aspirin was associated with a lower rate of high on-treatment platelet reactivity than was clopidogrel plus aspirin in Asian patients who had had a minor stroke or high-risk transient ischemic attack (TIA) in a new study.

The PRINCE study wasn't powered for clinical outcomes, but there was a trend toward fewer strokes at 90 days with ticagrelor vs clopidogrel. However, this finding was not statistically significant. 

The results were presented at the International Stroke Conference (ISC) 2018 by Yilong Wang, MD, Beijing Tiantan Hospital, China.

Patients experiencing a minor stroke or TIA have a high risk for recurrent stroke and are treated with antiplatelet agents to reduce this risk, Wang explained.  The previous CHANCE trial, also conducted in a Chinese population, showed a lower rate of recurrent stroke with a combination of clopidogrel and aspirin than with aspirin alone. 

But clopidogrel has a highly variable effect and is less active in patients carrying the CYP2C19 loss-of-function gene. Indeed, a subgroup analysis of the CHANCE study showed no benefit of clopidogrel over aspirin in patients carrying this allele, which is more common in East Asian populations. An alternative agent, such as ticagrelor, may be more appropriate for these patients, he suggested.

The PRINCE study, conducted at 26 centers in China, randomly assigned 675 patients to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg loading dose, 75 mg daily thereafter) on the background of aspirin (100 mg daily for the first 21 days).

Results showed that at 90 days, the primary endpoint — high on-treatment platelet reactivity — occurred in 12.5% of the ticagrelor group vs 29.7% of the clopidogrel group (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.22 - 0.52; P < .001).

In patients with any loss-of-function CYP2C19 allele, high on-treatment platelet reactivity occurred in 10.8% of the ticagrelor group vs 35.4% of the clopidogrel group (OR, 0.22; 95% CI, 0.12 - 0.40; P < .001).

The secondary endpoint, stroke, occurred in 6.3% of the ticagrelor group and 8.8% of the clopidogrel group (hazard ratio, 0.70; 95% CI, 0.40 - 1.22; P = .20).

Rates of major or minor bleeding did not significantly differ between the ticagrelor and clopidogrel groups (4.8% vs 3.5%; P = .42), but minimal bleeding was increased in the ticagrelor group (19.0% vs 10.6%; P = .003).

Commenting on the study for Medscape Medical News, Bruce Ovbiagele, MD, chair of the ISC 2018 meeting, said, "It does appear that ticagrelor could be a step forward, especially for people who have the clopidogrel loss-of-function allele. But this study had a surrogate marker (platelet reactivity) as its primary endpoint, so ideally I would like to see a larger trial with clinical outcomes as the primary endpoint. But, yes, I would consider using ticagrelor for a patient with the CYP2C19 loss-of-function gene."

He added that the use of clopidogrel in this situation has not become routine yet in the United States. 

"The CHANCE trial was just one study and was done in a Chinese population, which is known to have a higher incidence of the CYP2C19 loss-of-function gene," he said. "So there is now another US study underway — POINT —  looking to confirm the results. We would like to see if the result can be replicated in a more heterogenous group."

Also commenting on the study, Ralph Sacco, MD, Miller School of Medicine, Miami, Florida, said the PRINCE study was encouraging but preliminary. 

"This trial just shows that ticagrelor is a good antiplatelet agent," Sacco told Medscape Medical News. "The main outcome was not clinical, so this trial probably won't have much impact on clinical practice, especially in the West. It does show that ticagrelor had a better on effect on platelets in Asian patients, but we have to remember that Asian patients have a much higher incidence of the clopidogrel nonresponsiveness gene."

"In this study ticagrelor looked better than clopidogrel in both those with that gene and those without that gene," he noted. "That was an interesting finding. It may be more efficacious all round, but we need more data."  

He added that while there is a place for ticagrelor in coronary heart disease, "we don't have grade A evidence in stroke yet. The SOCRATES trial is the best study to date of ticagrelor in stroke. This compared ticagrelor with aspirin but just missed the primary endpoint, so it didn't get approval, but it is used occasionally for patients who have the clopidogrel nonresponsiveness genotype."

The PRINCE trial was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain Disorders, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. Wang has disclosed no relevant financial relationships. 

International Stroke Conference (ISC) 2018. Abstract LB 8.  

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