In recent years, with the progress of antithrombotic therapy, antiplatelet drugs such as aspirin and clopidogrel have been widely used. Although they have significantly improved the near and long-term prognosis of acute and chronic cardiac thrombotic events, however, the complications of bleeding have also gradually increased and become one of their non-cardiac complications, especially gastrointestinal bleeding (GIB) is the most common, which not only brings great difficulties and contradictions to the treatment, but also affects the patient’s The prognosis and the quality of life of patients are affected. The risk of GIB bleeding is greatly increased when two antiplatelet drugs, aspirin and clopidogrel, are combined. In response to this phenomenon, the 2008 American Heart Association/American Gastroenterological Association/American Heart Association guidelines recommended the addition of a proton pump inhibitor (PPI) for patients receiving dual antiplatelet therapy to reduce the risk of gastrointestinal bleeding. However, in 2006 Gilard unexpectedly found that patients taking PPI omeprazole had significantly higher vasodilator-stimulated phosphoprotein (VASP) values than those not taking it, suggesting for the first time that PPI omeprazole could reduce the antiplatelet biological effects of clopidogrel, and hypothesizing that the possible mechanism was that PPI also undergoes CYP2C19 metabolism, inhibiting the CYP2C19 pathway and interfering with the conversion of clopidogrel to active It was hypothesized that the possible mechanism is that PPI is also metabolized by CYP2C19, inhibiting the CYP2C19 pathway and interfering with the conversion of clopidogrel to active products, thus inhibiting the inhibitory effect of clopidogrel on platelet aggregation. Two large studies published in early 2009 also showed that the combination of clopidogrel and PPI for ACS increased the risk of death and rehospitalization. In response, the FDA issued a warning in January 2009 about the use of clopidogrel in combination with PPIs and recommended that the combination be considered with caution based on a full assessment of the risk/benefit ratio. Clopidogrel is a drug precursor that can only irreversibly bind to platelet ADP receptors and thus inhibit platelet aggregation by oxidative hydrolysis through cytochrome P450 (CYP) isozymes such as CYP3A4 and 2C19, which are metabolized to form a pharmacologically active derivative. CYP2C19 is the main metabolizing enzyme of clopidogrel bioactivity conversion, and the activity of CYP2C19 plays a decisive role in the conversion of clopidogrel activity. PPI is also metabolized in the liver mainly by CYP2C19 and 3A4 isoenzymes, and drug interactions may occur when PPI is combined with clopidogrel due to common competition for the same binding sites of CYP450 isoenzymes, the extent and results of which depend on the relative affinity of CYP450 isoenzymes. However, most of the above-mentioned reports on clopidogrel-PPI interactions are observational clinical studies with many confounding factors and weak evidence, and the conclusions of different PPIs are inconsistent. attenuate the antiplatelet effect of clopidogrel, whereas the other two combinations were relatively safe and effective. The COGENT study published at the end of 2009 showed only a mild increase in the risk of infarction or death with no statistically significant difference, but the application of a PPI significantly prevented gastrointestinal events; the study also looked at the effect of clopidogrel in combination with a PPI on the antiplatelet efficacy of clopidogrel The study also looked at the effect of the combination of clopidogrel and PPI on the antiplatelet efficacy of clopidogrel, and different PPIs were used, showing that there are differences between different PPIs. The professor’s study showed showed that five PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole, and rabeprazole) had different competitive inhibition of CYP2C19 activity, with lansoprazole having the strongest inhibition and pantoprazole and rabeprazole being milder. Omeprazole is relatively completely metabolized, mainly through CYP2C19 and CYP3A4. The affinity of the parent compound for CYP2C19 is almost 10 times greater than that for CYP3A4, and the potency of the metabolic enzyme effects of drug interactions published by the FDA on January 5, 2006 also showed that omeprazole has potent inhibitory activity against CYP2C19. Although esomeprazole is also metabolized mainly by CYP2C19 and the rest by CYP3A4, it has different effects on drug interactions due to the different proportions of this diastase mediating the metabolism of esomeprazole and omeprazole and the different relative affinities with the isoenzymes, which cause fewer drug interactions compared to omeprazole. Lansoprazole has essentially the same metabolic mechanism as omeprazole, but has very potent inhibitory activity against CYP2C19. Pantoprazole differs from omeprazole and lansoprazole in that it has a transsulfuration effect during metabolism and a low affinity for CYP450-dependent enzymes, especially for CYP2C19 inhibition. In addition, pantoprazole has a unique phase II metabolic pathway, which allows it to be metabolized by the phase II pathway when other drugs are metabolized in phase I. This makes it less susceptible to competitive drug metabolism and reduces drug-drug interactions in vivo. Therefore, numerous studies have found no clinically significant interactions with pantoprazole. Although rabeprazole is also a benzimidazole derivative, its metabolic pathway is different. Its main metabolic pathway is the formation of rabeprazole thioether by non-enzymatic degradation, while CYP2C19 and CYP3A4 are rarely involved and may not have specific CYP450 isoenzyme effects, thus minimizing the effect of drug interactions as far as PPI is concerned. The current level and strength of evidence regarding the interaction between PPIs and clopidogrel is not yet strong enough to change existing clinical practice and guidelines. The new ESC 2011 guidelines suggest that concomitant administration of proton pump inhibitors (PPIs, preferably with the exception of omeprazole) in patients with a history of prior peptic ulcer or GI bleeding is also recommended for patients with other multiple risk factors (e.g., H. pylori positive, age greater than or equal to 65 years, or concurrent anticoagulation or glucocorticoid treatment). Therefore, we should pay more attention to balancing antithrombotic therapy with bleeding risk in our clinical work: Clopidogrel should be used strictly according to guideline norms, and if there is a drug conflict problem, the first concern should be the patient’s life safety and the option of further management. Perform bleeding tests, including fecal occult blood and routine blood work, and endoscopy if necessary, in all those treated with clopidogrel. Add a PPI in case of bleeding and continue close monitoring; if active bleeding remains, active management, such as discontinuation of clopidogrel or endoscopic intervention, is required. Prescribe PPI only to high-risk individuals with a history of prior bleeding, and intermittently or as necessary, and use a PPI that is less dependent on CYP2C19. In conclusion, from the cardiovascular physician’s perspective, clopidogrel has clear benefit, and its combination with aspirin is the standard treatment recommended by national and international guidelines for patients with ACS and post-PCI; however, its bleeding risk should be fully evaluated; individualized for high-risk patients However, the risk of bleeding should be fully evaluated; individualized treatment should be adopted for high-risk patients, and PPI should be used as needed to combine the benefits and risks and ensure the safety of patients’ lives first and foremost.