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Comparison between clopidogrel and ticagrelor in CYP2C19 loss-of-function alleles coronary artery disease and stroke
Mahmoud Elsayed1, Mostafa Hossam El Din Moawad2,3, Mohammed Elkholy4
1Stroke and Neurovascular Regulation Laboratory, 149 13 Street, Room 6405, Charlestown, MA, 02129, USA.
Insights
Ticagrelor is preferred over clopidogrel for patients with coronary artery disease (CAD) and stroke who have CYP2C19 loss-of-function (LOF) alleles. Ticagrelor reduces thrombosis/embolism, stroke, and myocardial infarction (MI) risks without increasing bleeding events.
Area of Science:
- Cardiology
- Pharmacogenomics
- Clinical Trials
Background:
- Patients with coronary artery disease (CAD) and stroke often receive antiplatelet therapy.
- CYP2C19 loss-of-function (LOF) alleles affect clopidogrel metabolism, potentially reducing its efficacy.
- Ticagrelor may offer superior outcomes in these patients compared to clopidogrel.
Purpose of the Study:
- To systematically review and meta-analyze the efficacy and safety of ticagrelor versus clopidogrel in CAD and stroke patients with CYP2C19 LOF alleles.
- To compare the risk of thrombosis/embolism, myocardial infarction (MI), and stroke between ticagrelor and clopidogrel.
- To assess bleeding risks associated with ticagrelor and clopidogrel in this patient population.
Main Methods:
- Systematic review and meta-analysis of eligible publications from PubMed, Web of Science, and Scopus.
- Search strategy included keywords: "Ticagrelor", "Clopidogrel", and "CYP2C19".
- Odds ratio (OR) with 95% confidence intervals (CI) used for effect estimation; p-value < 0.05 considered significant.
Main Results:
- Clopidogrel use was associated with a significantly increased risk of thrombosis/embolism (OR=1.78, p=0.02), stroke (OR=1.43, p<0.00001), and MI (OR=1.53, p=0.0003) compared to ticagrelor.
- No significant difference in stroke or CAD incidence (OR=0.98, p=0.87) was observed between the groups.
- No significant difference in minor bleeding (OR=0.66, p=0.08) or any bleeding (OR=0.81, p=0.3) was found, despite high heterogeneity (I²=88%).
Conclusions:
- Ticagrelor demonstrates a preference over clopidogrel in stroke or CAD patients with CYP2C19 LOF alleles.
- Ticagrelor significantly reduces the incidence of thrombosis/embolism, stroke, and MI.
- Ticagrelor appears safe regarding bleeding risk, with no significant increase in minor or major bleeding events compared to clopidogrel.
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 CYP2C19 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 CYP2C19 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 CYP2C19 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 I2 = 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 CYP2C19 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.
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