Lower chance of new stroke with ticagrelor vs clopidogrel in patients without ICAS

A post hoc analysis of the CHANCE-2 randomized controlled trial (RCT) demonstrates that ticagrelor-aspirin combination therapy is associated with a significantly lower risk of new stroke within 90 days vs the clopidogrel-aspirin combination in Chinese CYP2C19 loss‐of‐function allele carriers with minor stroke or transient ischaemic attack (TIA) without intracranial artery stenosis (ICAS).

“Although ticagrelor or ticagrelor-aspirin has demonstrated superiority to aspirin alone in patients with atherosclerotic stenosis in subgroup analyses of the SOCRATES and THALES trials, no previous studies have compared ticagrelor with clopidogrel in Asian patients who are carriers of the CYP2C19 loss‐of‐function alleles and have ICAS and ischaemic stroke or TIA,” wrote the researchers. “[In addition,] whether selection of antiplatelet therapy based on genetic testing is effective for preventing recurrent stroke in patients with or without ICAS remains unclear.” [Lancet Neurol 2017;16:301-310; Stroke 2020;51:3504-3513]

A total of 5,893 patients (median age, 64.8 years; female, 33.9 percent) with CYP2C19 loss‐of‐function alleles and available imaging results of intracranial arteries were recruited from the CHANCE-2 trial and allocated to receive ticagrelor-aspirin (n=2,956) or clopidogrel-aspirin (n=2,937) combination therapy. Symptomatic ICAS (sICAS) was present in 27.7 percent of patients, while 12.7 percent of patients had asymptomatic ICAS (asICAS). [J Am Heart Assoc 2023;12:e031611]

New stroke within 90 days of the first event occurred in 4.9 percent, 10.5 percent and 7.7 percent of patients without ICAS, with sICAS and with asICAS, respectively. Compared with the cumulative risk of new stroke among patients without ICAS, the hazard ratios (HRs) for stroke recurrence in the sICAS and asICAS groups were 2.17 (95 percent confidence interval [CI], 1.74–2.70) and 1.59 (95 percent CI, 1.17–2.17), respectively, after controlling for the randomization group factors.

New stroke within 90 days occurred in 3.5 percent and 6.3 percent of patients without ICAS in the ticagrelor-aspirin and clopidogrel-aspirin groups, respectively (HR, 0.57; 95 percent CI, 0.41–0.78). Among patients with sICAS, new stroke within 90 days occurred in 9.7 percent and 11.3 percent in the respective treatment groups (HR, 0.77; 95 percent CI, 0.56–1.05), while these rates were 7.4 percent and 7.9 percent for patients with asICAS (HR, 0.77; 95 percent CI, 0.43–1.38). “Patients without ICAS obtained a significantly greater benefit from ticagrelor-aspirin [vs clopidogrel-aspirin] after minor ischaemic stroke or TIA, but there was no statistically significant difference between treatments in patients with sICAS or asICAS,” reported the researchers.

No significant difference in moderate or severe bleeding was found among patients across different ICAS groups. However, the risk of any bleeding (6.2 percent vs 2.3 percent) and mild bleeding (5.9 percent vs 2.0 percent) was nearly three times greater in patients without ICAS receiving ticagrelor-aspirin vs clopidogrel-aspirin treatment. No significant difference was observed for other safety outcomes.