Ticagrelor–ASA reduced stroke risk by 30% (HR 0.70) compared to clopidogrel–ASA in patients with Lp(a) <30 mg/dL, with no benefit in those with Lp(a) ≥30 mg/dL.
Does ticagrelor plus acetylsalicylic acid reduce stroke within 1 year compared to clopidogrel plus acetylsalicylic acid in patients with minor stroke or TIA carrying the CYP2C19 loss-of-function allele, and is this effect modified by baseline Lp(a) levels?
In CYP2C19 loss-of-function carriers with minor stroke or TIA, ticagrelor-aspirin reduces 1-year stroke risk compared to clopidogrel-aspirin only in patients with Lp(a) <30 mg/dL.
Background: Lipoprotein (a) is recognized as an independent risk factor for atherosclerotic cardiovascular disease, with its interaction with several platelet receptors offering biological plausibility for a pro-aggregatory effect. Our aim was to evaluate the impact of Lp(a) on the efficacy and safety of ticagrelor–aspirin compared to clopidogrel–aspirin treatment. Methods: This is a post-hoc analysis obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. The CHANCE-2 trial was a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, randomized patients with minor stroke or TIA who carried the CYP2C19 loss-of-function allele to receive either ticagrelor– acetylsalicylic acid (ASA) or clopidogrel– ASA. Patients were classified with Lp(a) levels <30 mg/dL and ≥30 mg/dL. The primary efficacy outcome of the study was stroke within 1 year, and the safety outcome was severe or moderate bleeding. Results: A total of 5915 patients were enrolled in this study. The median Lp(a) was 20.35 (9.70– 43.98) mg/dL. The proportion of patients with an Lp(a) level ≥30 mg/dL was 36.33%. Ticagrelor–ASA was associated with a significantly lower rate of stroke within 1 year among patients with Lp(a)＜30 mg/dL (HR 0.70, 95% CI 0.56 -0.87), but not among those with Lp(a) ≥30 mg/dL (HR1.01, 95% CI 0.77-1.32), compared with clopidogrel aspirin(p =0.039 for interaction).Safety outcome of severe or moderate bleeding did not differ in Lp(a) groups. Conclusions: This post hoc analysis of the CHANCE-2 trial suggests that Lp(a) may serve as a potential biomarker for identifying CYP2C19 loss-of-function carriers with minor stroke or TIA who benefit more from ticagrelor–aspirin therapy compared to clopidogrel–aspirin therapy.
Dai et al. (2026) studied this question. Ticagrelor–ASA reduced stroke risk by 30% (HR 0.70) compared to clopidogrel–ASA in patients with Lp(a) <30 mg/dL, with no benefit in those with Lp(a) ≥30 mg/dL.