Why the study?
Body mass index may affect the response to platelet P2Y12 receptor inhibitors, but its influence on the efficacy and safety of ticagrelor versus clopidogrel for secondary prevention after minor stroke or TIA was unclear.
Does ticagrelor-ASA improve stroke outcomes compared to clopidogrel-ASA in obese versus nonobese patients with minor stroke or TIA carrying CYP2C19 loss-of-function alleles?
Does ticagrelor-ASA improve stroke outcomes compared to clopidogrel-ASA in obese versus nonobese patients with minor stroke or TIA carrying CYP2C19 loss-of-function alleles?
In patients with minor ischemic stroke or TIA carrying a CYP2C19 loss-of-function allele, ticagrelor-ASA therapy provides greater clinical benefit than clopidogrel-ASA in reducing stroke risk specifically among those with obesity.
BMI-stratified antiplatelet selection may be warranted in CYP2C19 LOF carriers with minor stroke/TIA; leaves open need for prospective confirmation of interaction.
Background: Body mass index (BMI) may affect the response to platelet P2Y₁₂ receptor inhibitors. We aimed to explore whether BMI influenced the efficacy and safety of ticagrelor and clopidogrel for secondary prevention of minor ischemic stroke or transient ischemic attack (TIA) among patients enrolled in the CHANCE-2 (Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial. Methods: In a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, we 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. We classified patients into obese (BMI ≥ 28) or nonobese (BMI < 28) groups. The primary efficacy outcome was stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results: Among 6412 patients, 876 were classified as obese and 5536 were classified as nonobese. Compared with clopidogrel–ASA, ticagrelor–ASA was associated with a significantly lower rate of stroke within 90 days among patients with obesity (25 [5.4%] v. 47 [11.3%]; hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30–0.87), but not among those in the nonobese group (166 [6.0%] v. 196 [7.0%]; HR 0.84, 95% CI 0.69–1.04) The interaction of treatment and BMI group was significant (p for interaction = 0.04). We did not observe any difference by BMI group in rates of severe or moderate bleeding (9 [0.3%] v. 10 [0.4%] in the nonobese group; 0 [0.0%] v. 1 [0.2%] in the obese group; p for interaction = 0.99). Interpretation: In this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA, compared with clopidogrel–ASA, patients with obesity received more clinical benefit from ticagrelor–ASA therapy than those without obesity. Trial registration: Clinicaltrials.gov, no. NCT04078737.
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Zhang et al. (2023) studied this question.
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