Key result
Prasugrel or ticagrelor significantly reduced the risk of MACEs compared to clopidogrel in ACS patients with CYP2C19 loss-of-function alleles undergoing PCI (RR 0.58; 95% CI 0.45-0.76; P<0.0001).
Why the study?
The most effective antiplatelet treatments for ACS patients carrying CYP2C19 loss-of-function alleles undergoing PCI remained debated and conflicting.
Do alternative P2Y12 receptor blockers (prasugrel or ticagrelor) reduce major adverse cardiovascular events compared to clopidogrel in acute coronary syndrome patients with CYP2C19 loss-of-function alleles undergoing PCI?
Meta-Analysis (n=16,132)
Do alternative P2Y12 receptor blockers (prasugrel or ticagrelor) reduce major adverse cardiovascular events compared to clopidogrel in acute coronary syndrome patients with CYP2C19 loss-of-function alleles undergoing PCI?
Relative Risk: 0.58 (95% CI 0.45–0.76)
p-value: p=<0.0001
In ACS patients with CYP2C19 loss-of-function alleles undergoing PCI, genotype-guided therapy with prasugrel or ticagrelor significantly reduces MACE, cardiovascular death, and MI without increasing bleeding risk compared to clopidogrel.
Alternative P2Y12 inhibitors reduce ischemic risk vs clopidogrel in CYP2C19 LoF carriers post-PCI; supports genotype-guided selection in ACS.
The most effective antiplatelet treatments for acute coronary syndrome (ACS) patients carrying CYP2C19 loss-of-function (LoF) alleles undergoing percutaneous coronary intervention (PCI) is still debating and conflicting. It was aimed to compare the efficacy and safety endpoints for these patients treated with alternative P2Y12 receptor blockers (e.g. prasugrel or ticagrelor) against clopidogrel. Literature was searched in PubMed, Cochrane library, Synapse and 1000 Genomes databases following PRISMA guidelines for identifying relevant studies. Aggregated risk was estimated by RevMan software using either fixed/random-effects models where P values<0.05 (two-sided) were considered statistically significant. Nine studies comprising 16,132 ACS patients undergoing PCI were included in this analysis in which 2,746 and 2,640 patients were in the CYP2C19 LoF clopidogrel and alternatives treatment group, respectively. It was demonstrated that patients treated with prasugrel or ticagrelor significantly reduced the risk of MACEs (RR 0.58; 95% CI 0.45–0.76; P<0.0001) as compared to patients with clopidogrel where both groups carrying CYP2C19 LoF alleles. Subgroup analysis showed that prasugrel or ticagrelor significantly reduced the risk of cardiovascular death (RR 0.44; 95% CI: 0.25–0.74; P=0.002) and MI (RR 0.60; 95% CI: 0.44–0.81; P=0.0008) while other clinical outcomes were not found statistically significant between these two groups; stroke (RR 0.77; 95% CI: 0.43–1.38; P =0.39), stent thrombosis (RR 0.67; 95% CI: 0.38–1.18; P =0.17), unstable angina (RR 0.55; 95% CI: 0.13–2.33; P =0.42), revascularisation (RR 0.79; 95% CI: 0.28 Siller-Matula JM, Lang IM, Neunteufl T, Kozinski M, Maurer G, Linkowska K, Grzybowski T, Kubica J, Jilma B. Interplay between genetic and clinical variables affecting platelet reactivity and cardiac adverse events in patients undergoing percutaneous coronary intervention. PLoS ONE 2014;9(7). https://doi.org/10.1371/journal.pone.0102701[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]–2.24; P=0.66). Bleeding events were not found significantly different between these groups (RR 1.06; 95% CI: 0.88–1.28; P=0.55). Considering efficacy and safety, alternative antiplatelets (e.g. prasugrel or ticagrelor) may be regarded as better treatment option as compared to clopidogrel for ACS patients undergoing PCI.
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Biswas et al. (2020) conducted a meta-analysis in Acute coronary syndrome (ACS) (n=16,132). Prasugrel or ticagrelor vs. Clopidogrel was evaluated on MACEs (RR 0.58, 95% CI 0.45-0.76, p=<0.0001). Prasugrel or ticagrelor significantly reduced the risk of MACEs compared to clopidogrel in ACS patients with CYP2C19 loss-of-function alleles undergoing PCI (RR 0.58; 95% CI 0.45-0.76; P<0.0001).
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