Comparison between clopidogrel and ticagrelor in CYP2C19 loss-of-function alleles coronary artery disease and stroke patients: a meta-analysis

It is suggested that in patients with coronary artery diseases (CAD) and stroke, the use of ticagrelor and aspirin may perform better than clopidogrel and aspirin regarding the risk of thrombosis/embolism, including recurrent myocardial infarction (MI) and cardiovascular death, especially in those carrying CYP 2 C19 loss-of-function (LOF) alleles. Therefore, we conducted the present systematic review and meta-analysis to investigate the effect of clopidogrel and ticagrelor in CAD and stroke patients with CYP 2 C19 LOF alleles (poor metabolizers of clopidogrel). We performed the current systematic review and meta-analysis by searching for all eligible publications on PubMed, Web of Science, and Scopus from inception to November 2024. A search strategy employing three primary keywords in conjunction with their corresponding Medical Subject Headings (MeSH) terms: “Ticagrelor” AND “Clopidogrel” AND “CYP2C19” (PROSPERO ID CRD420251050533). We implemented the odds ratio (OR) as an effect estimate for the dichotomous variables. The analysis was done at 95% confidence intervals (CI), and the p -value was significant if it was less than or equal to 0.05. Using clopidogrel was associated with an increased risk of thrombosis/embolism compared with ticagrelor, showing OR = 1.78 (95%CI, 1.08, 2.95; p = 0.02). Also, clopidogrel led to an increased risk of stroke, whether when used in stroke or CAD patients with CYP 2 C19 LOF alleles, compared with ticagrelor, with an overall OR = 1.43 (95%CI, 1.23, 1.66; p < 0.00001) and a higher rate of MI with OR = 1.53 (95%CI, 1.22, 1.92; p = 0.0003). No significant difference was observed between the two groups (clopidogrel and ticagrelor) in stroke or CAD patients with OR = 0.98 (95%CI, 0.79, 1.22; p = 0.87). Also, no significant difference was observed between both groups regarding the risk of minor bleeding in stroke or CAD patients with OR = 0.66 (95%CI, 0.42, 1.05; p = 0.08) and any types of bleeding (major or minor bleeding) with overall OR = 0.81 (95%CI, 0.54, 1.21; p = 0.3) and I 2 = 88%, p < 0.00001. The meta-analysis of the selected articles indicated a preference for ticagrelor over clopidogrel in patients with stroke or CAD possessing CYP 2 C19 LOF alleles. The reduced incidence of thrombosis/embolism and associated events, such as stroke and MI, was noted in individuals administered ticagrelor in comparison to those receiving clopidogrel. Bleeding remains a concern with ticagrelor; however, current studies indicate its safety since there are no significant changes in the risk of minor and major bleeding and ICH compared to clopidogrel.