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Ticagrelor/aspirin combo reduces HOPR rate after minor stroke or TIA

Roshini Claire Anthony
20 Feb 2018

The use of a ticagrelor/aspirin combination was more successful than a clopidogrel/aspirin combination in reducing the rate of high on-treatment platelet reactivity (HOPR) in patients with a recent minor stroke or transient ischaemic attack (TIA), according to results of the PRINCE* trial conducted in China.

In this multicentre (26 centres in China), open-label trial, 675 patients aged 40–80 years within 24 hours of symptom onset of an acute minor stroke or TIA were randomized to receive either ticagrelor (180 mg loading dose [day 1] followed by 90 mg BID) or clopidogrel (300 mg loading dose [day 1] followed by 75 mg QD) along with aspirin (100 mg QD for the first 21 days) for 90 days.

Patients with an indication for anticoagulation drugs, contraindications to any of the study drugs, or undergoing endovascular therapy were excluded.

HOPR at 90 days was lower among patients who had received ticagrelor plus aspirin compared with clopidogrel plus aspirin (12.5 percent vs 29.7 percent, odds ratio [OR], 0.34, 95 percent confidence interval [CI], 0.22–0.52; p<0.001). [ISC 2018, abstract LB8]

The reduced HOPR among patients in the ticagrelor/aspirin arm vs the clopidogrel/aspirin arm was particularly evident in patients with loss of function of the CYP2C19 allele (10.8 percent vs 35.4 percent, OR, 0.22, 95 percent CI, 0.12–0.40; p<0.001).

The incidence of stroke at 90 days was comparable between patients on the ticagrelor/aspirin and clopidogrel/aspirin combinations (6.3 percent vs 8.8 percent, hazard ratio [HR], 0.70, 95 percent CI, 0.40–1.22; p=0.20).

While the incidence of any bleeding was higher in the ticagrelor/aspirin vs the clopidogrel/aspirin group (22.3 percent vs 14.2 percent, HR, 1.65; p=0.007), there was no significant between-group difference in terms of major (1.5 percent vs 1.2 percent, HR, 1.27; p=0.72) or minor bleeding (3.3 percent vs 2.4 percent, HR, 1.40; p=0.47).

The most common adverse events leading to treatment discontinuation were dyspnoea and epistaxis, both of which occurred more frequently in the ticagrelor/aspirin than in the clopidogrel/aspirin arm (4.2 percent vs 0 percent; p=0.0001 and 1.8 percent vs 0 percent; p=0.04, respectively).

“Ticagrelor plus aspirin reduced HOPR in more patients at 90 days, compared with clopidogrel plus aspirin in patients with minor stroke or high-risk TIA, especially for carriers of the CYP2C19 loss of function alleles,” said study investigator Dr Wang Yilong from the Beijing Tiantan Hospital, Beijing, China, who presented the results at the International Stroke Conference 2018 (ISC 2018) in Los Angeles, California, US.

While not statistically significant, there were numerically fewer strokes at 90 days among patients in the ticagrelor/aspirin arm, particularly with regards to the left atrial appendage subtype, and a comparable incidence of major and minor bleeding between the two groups, said Wang.

He acknowledged that the open-label design may have affected the findings, while highlighting the infeasibility of a double-blinded study design. Furthermore, HOPR was considered a “surrogate endpoint”; hence, more research is required to establish clinical efficacy of the treatment, he said.

 

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