PRINCE: Ticagrelor plus aspirin beneficial in minor stroke, high-risk TIA

Patients with minor stoke or high-risk transient ischemic attack who were treated with ticagrelor plus aspirin had reduced high on-treatment platelet reactivity, fewer strokes and more minimal bleeding events compared with those treated with clopidogrel plus aspirin, according to a late-breaking clinical trial presented at the International Stroke Conference.

Yilong Wang, MD, PhD, of the department of neurology at Beijing Tiantan Hospital at Capital Medical University, and colleagues analyzed data from the PRINCE trial of 675 patients from 26 sites who had an ischemic minor stroke or TIA within 24 hours, had no indication for anticoagulation, had no contraindication to clopidogrel, ticagrelor (Brilinta, AstraZeneca) or acetylsalicylic acid and were not administered IV tissue plasminogen activator.

Patients were assigned a loading dose of 180 mg ticagrelor with 100 mg to 300 mg aspirin (n = 336; median age, 62 years; 27% women) or 300 mg clopidogrel with 100 mg to 300 mg aspirin (n = 339; median age, 61 years; 27% women). Each group then received a regular dose of the assigned medication for 3 weeks, which was 90 mg ticagrelor twice per day or 75 mg clopidogrel daily plus aspirin 100 mg daily. Aspirin was dropped from the regimens between days 21 and 90.

Platelet function tests were performed at baseline and periodically up to 90 days.

The primary efficacy outcomes of interest were P2Y12 reaction units at 90 days and high on-treatment platelet reactivity, and secondary efficacy outcomes of interest were stroke during 90 days and a composite of vascular events, which were defined as MI, any stroke and vascular death during 90 days.

The primary safety outcomes of interest were major or minor bleeding, and secondary safety outcomes of interest were total mortality or intracranial hemorrhage.

The trial was terminated by the data and safety monitoring board after it reviewed the results of the interim analysis from August 2015 to March 2017.

P2Y12 reaction units decreased rapidly in the ticagrelor group compared with the clopidogrel group at 2 hours (45.75 vs. 222.32) and remained consistent at 24 hours (36.71 vs. 182.67), 7 days (46.94 vs. 166.63) and 90 days (69.24 vs. 175.44). At 90 days, high on-treatment platelet reactivity decreased more in the ticagrelor group (12.5%) vs. the clopidogrel group (29.7%; P < .001).

“It’s very interesting [that] there was those response relationships between the number of the CYP2C19 loss-of-function allele and the odds ratio of the high on-treatment platelet reactivity,” Wang said during the press conference. “The patient carries more loss-of-function allele and having high rate of platelet aggregation in clopidogrel, but not observed in ticagrelor.”

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Patients in the ticagrelor group had fewer stroke events (6.3%) compared with the clopidogrel group (8.8%; HR = 0.7; 95% CI, 0.4-1.22).

“The majority of stroke events occurred in the first weeks, but [was] not a significant difference,” Wang said.

Fewer strokes in the left atrial appendage occurred in the ticagrelor group (6%) compared with the clopidogrel group (13.1%; HR = 0.45; 95% CI, 0.2-0.98). This was not seen in strokes in non-left atrial appendage, as more patients assigned ticagrelor had these strokes (8.1%) vs. patients assigned clopidogrel (7.4%; HR = 1.1; 95% CI, 0.46-2.63; P for interaction = .13).

Three deaths occurred in patients assigned ticagrelor and two patients assigned clopidogrel (HR = 1.5; 95% CI, 0.25-9). Although there was no significant difference in major bleeding in the ticagrelor (1.5%) and clopidogrel groups (1.2%), minimal bleeding was significantly higher in the ticagrelor group compared with the clopidogrel group (19% vs. 10.6%; HR = 1.86; 95% CI, 1.24-2.8).

Adverse events that led to drug discontinuation were dyspnea (4.2%) and epistaxis (1.8%) in the ticagrelor group. These events did not occur in the clopidogrel group.

“Ticagrelor plus aspirin reduced [high on-treatment platelet reactivity] 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,” Wang said. – by Darlene Dobkowski

Reference:

Wang Y, et al. LB8. Presented at: International Stroke Conference; Jan. 23-26, 2018; Los Angeles.

Disclosures: The study was sponsored by AstraZeneca. Wang reports no relevant financial disclosures.