1. In this post-hoc analysis of the CHANCE-2 trial, ticagrelor-acetylsalicylic acid was more beneficial compared to clopidogrel-acetylsalicylic acid for preventing recurrent stroke among those with elevated levels of homocysteine and CYP2C19 LOF mutations. 

Evidence Rating Level: 2 (Good) 

Elevated homocysteine levels are associated with increased hemostasis, progression of atherosclerosis, and greater risk of initial or recurrent stroke. Little is known about whether homocysteine levels impact the effectiveness of dual antiplatelet treatments for preventing stroke. Researchers aimed to assess the association between homocysteine levels and the efficacy of ticagrelor-acetylsalicylic acid (ASA) vs. clopidogrel-ASA for patients with prior minor stroke or transient ischemic attack (TIA) and CYP2C19 loss-of-function (LOF) alleles. 2740 participants from the Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events–II (CHANCE-2) Trial were included in this analysis. The participants were randomly assigned to treatment with ticagrelor-ASA or clopidogrel-ASA. In addition, the participants were categorized as having elevated or non-elevated levels of homocysteine. Among those with elevated homocysteine, ticagrelor-ASA compared to clopidogrel-ASA was associated with a reduced risk of recurrent stroke (74 [5.3%] v. 119 [8.5%]; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.45–0.81). This association was not found for those without elevated homocysteine levels. The benefit of ticagrelor-ASA for reducing the risk of recurrent stroke increased as the homocysteine level increased (p = 0.04 for interaction). No association was found between the homocysteine level and the risk of bleeding while on dual antiplatelet therapy. A limitation of this study is that there was a very low incidence of bleeding during the trial period, which reduces the statistical power for assessing the safety risks of different medication regimens. Overall, this study demonstrates that ticagrelor-ASA was more beneficial compared to clopidogrel-ASA for preventing recurrent stroke among those with elevated levels of homocysteine and the CYP2C19 LOF mutation. 

Click to read the study in CMAJ

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