Genotype-guided ticagrelor/prasugrel versus clopidogrel therapy in stroke patients with CYP2C19 loss of function alleles: a systematic review and meta-analysis.

INTRODUCTION: Transient ischemic attack (TIA) or ischemic stroke (IS) patients may have recurrent stroke incidents, especially when carrying CYP2C19 Loss-of-Function (LoF) alleles and taking clopidogrel. Recent studies suggest using alternative antiplatelets, e.g., prasugrel, ticagrelor, in these patients. However, the aggregated risk of recurrent stroke or composite vascular events in CYP2C19 genotype-guided prasugrel/ticagrelor against clopidogrel therapy in such TIA/IS patients remained unexplored. METHODS: A database search was performed to retrieve relevant studies. RevMan software was used to calculate the risk ratio (RR), considering p < 0.05 statistically significant. RESULT: Six studies (14,124 TIA/IS patients) were considered. TIA/IS patients carrying CYP2C19 LoF alleles on ticagrelor/prasugrel therapy were associated with a significant reduction in the risk of composite vascular events (RR 0.76, 95% CI 0.66-0.89; p = 0.0004) and recurrent stroke (RR 0.76, 95% CI 0.64-0.90; p = 0.002) compared to the clopidogrel therapy. However, the bleeding events did not differ significantly (RR 0.91, 95% CI 0.65-1.27; p = 0.58) between the treatment groups. CONCLUSION: TIA/IS patients inheriting CYP2C19 LoF alleles taking ticagrelor/prasugrel may significantly optimize the overall clinical benefits compared to those who are taking clopidogrel by reducing composite vascular events and recurrent stroke without elevating the risk of bleeding events.