Ticagrelor-acetylsalicylic acid may reduce stroke risk further for obese patients than clopidogrel

1. For obese patients with minor stroke or transient ischemic attacks (TIA), subsequent therapy with ticagrelor-acetylsalicylic acid (ASA) was associated with lower risk of subsequent stroke compared to clopidogrel-ASA.

2. This difference in risk reduction was not observed in nonobese patients. 

Evidence Rating Level: 1 (Excellent)

The treatment of patients with minor ischemic stroke and TIA with dual antiplatelet therapy, namely clopidogrel and ASA or with ticagrelor and ASA, is well established as efficacious. In the Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial, ticagrelor-ASA therapy was more effective in reducing stroke risk compared to clopidogrel-ASA therapy in patients with minor ischemic stroke or TIA who carried CYP2C19 loss-of-function alleles. However, various factors, including obesity, can influence the efficacy of antiplatelet therapy. Therefore, this secondary analysis of the 6412 patients enrolled in the randomized, double-blind, multicentre CHANCE-2 trial aimed to evaluate the efficacy and safety of ticagrelor-ASA and clopidogrel-ASA as stratified by BMI. Patients diagnosed with an acute minor ischemic stroke or a high-risk TIA were randomly assigned in a 1:1 ratio within 24 hours of symptom onset to the ticagrelor-ASA group (n=3205) or clopidogrel-ASA group (n=3207). Patients with a BMI ≥ 28 (n=876, 13.7%) were classified as obese, while those with BMI < 24 and 24-28 were nonobese (n=5536, 86.3%). For each 5-unit increase in BMI, the hazard ratio (HR) of 90-day stroke with ticagrelor-ASA therapy, compared to clopidogrel-ASA, decreased by 17.98% (95% CI 17.97%-18.00%). Furthermore, compared with the clopidogrel-ASA group, ticagrelor–ASA had a significantly lower rate of stroke within 90 days in patients with obesity (HR 0.51, 95% CI 0.30–0.87), but not in nonobese patients (HR 0.84, 95% CI 0.69–1.04). The interaction between the treatment group and BMI was significant (p=0.04). Overall, these findings suggest that obese patients with minor ischemic stroke or TIA who are carriers of CYP2C19 loss-of-function alleles, experience a greater clinical benefit from ticagrelor–ASA therapy than with clopidogrel–ASA therapy.

Click to read the study in CMAJ

Image: PD

©2023 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.