Key result
Ticagrelor or prasugrel reduced the risk of major adverse cardiovascular events compared to clopidogrel in patients with CYP2C19 loss-of-function alleles (RR 0.524; 95% CI 0.375-0.731).
Why the study?
The study was conducted to compare the efficacy and safety of ticagrelor and prasugrel versus clopidogrel in CYP2C19 reduced-metabolizers.
Does ticagrelor or prasugrel reduce MACE compared to clopidogrel in coronary artery disease patients with CYP2C19 loss-of-function alleles?
Meta-Analysis (n=5,829)
Does ticagrelor or prasugrel reduce MACE compared to clopidogrel in coronary artery disease patients with CYP2C19 loss-of-function alleles?
Relative Risk: 0.524 (95% CI 0.375–0.731)
In patients with coronary artery disease and CYP2C19 loss-of-function alleles, using ticagrelor or prasugrel significantly reduces the risk of MACE compared to clopidogrel without significantly increasing bleeding risk.
Favors prasugrel or ticagrelor over clopidogrel for MACE in CYP2C19 reduced-metabolizers; reinforces genotype-guided P2Y12 selection.
AIM: We performed a systematic review and meta-analysis to compare the efficacy and safety of ticagrelor and prasugrel with those of clopidogrel in CYP2C19 reduced-metabolizers. METHODS: PubMed, Cochrane and Web of Science were systematically searched for randomized controlled trials or cohort studies up to January 2020. The primary endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, all-cause death, myocardial infarction (MI), stent thrombosis and stroke. The secondary endpoint was bleeding. Pooled effects were measured by relative risk (RR) with 95% confidence intervals (CIs). Publication bias was evaluated with Egger's regression test and adjusted by trim and fill method. RESULTS: Twelve studies comprising 5829 CV patients with CYP2C19 loss-of-function alleles were included. Patients who received ticagrelor or prasugrel showed a lower risk of MACE than those who received clopidogrel (RR 0.524; 95% CI: 0.375, 0.731). The former also had lower risks of CV death (RR 0.409; 95% CI: 0.177, 0.946), all-cause death (RR 0.441; 95% CI: 0.263, 0.739), MI (RR 0.554; 95% CI: 0.414, 0.741) and stent thrombosis (RR 0.587; 95% CI: 0.348, 0.988) than the latter patient group. The risk of stroke was not significantly different between patients receiving the alternatives and those receiving clopidogrel (RR 0.605; 95% CI: 0.257, 1.425). Major and minor bleeding risk was not significantly different between patients treated with alternatives and clopidogrel (RR 1.019; 95% CI: 0.827, 1.260 and RR 1.235; 95% CI: 0.581, 2.628, respectively). CONCLUSION: CYP2C19 reduced-metabolizers can expect better clinical outcome on using prasugrel or ticagrelor rather than clopidogrel.
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Yoon et al. (2020) conducted a meta-analysis in Coronary artery disease with CYP2C19 loss-of-function alleles (n=5,829). Ticagrelor or prasugrel vs. Clopidogrel was evaluated on Major adverse cardiovascular events (MACE), including cardiovascular death, all-cause death, myocardial infarction, stent thrombosis and stroke (RR 0.524, 95% CI 0.375, 0.731). Ticagrelor or prasugrel reduced the risk of major adverse cardiovascular events compared to clopidogrel in patients with CYP2C19 loss-of-function alleles (RR 0.524; 95% CI 0.375-0.731).
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