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

• Published in: European journal of clinical pharmacology Vol. 81; no. 9; pp. 1241 - 1256
• Main Authors: Elsayed, Mahmoud, Moawad, Mostafa Hossam El Din, Elkholy, Mohammed, Ahmed, Yousr, Nabgouri, Younes, Bahtiyarova, Gulnaz, Alkhawaldeh, Ibraheem M., Abouzid, Mohamed, Wagih, Reham M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2025; Springer Nature B.V
• Subjects: Acute coronary syndromes; Alleles; Aspirin; Bias; Biomedical and Life Sciences; Biomedicine; Bleeding; Blood platelets; Cardiovascular disease; Cerebral infarction; Clopidogrel; Clopidogrel - adverse effects; Clopidogrel - therapeutic use; Coronary artery disease; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Coronary vessels; Cytochrome P-450 CYP2C19 - genetics; Embolism; Embolisms; Heart diseases; Humans; Ischemia; Loss of Function Mutation; Meta-analysis; Mortality; Myocardial infarction; Observational studies; Performance evaluation; Pharmacology/Toxicology; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; Review; Statistical analysis; Stents; Stroke; Stroke - drug therapy; Stroke - genetics; Systematic review; Thrombosis; Ticagrelor - adverse effects; Ticagrelor - therapeutic use; Transient ischemic attack; Vein & artery diseases; Loss-of-function; Clopidogrel; Coronary; Stroke; Ticagrelor; CYP2 C19
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-025-03860-4

Background 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). Methods 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. Results 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. Conclusion 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.