According to WHO, thrombotic diseases, mainly atherosclerotic thrombosis, are the first cause of death in the world (about 22.3%), much higher than infectious diseases (19.1%) and tumors (12.5%). In China, cardiovascular diseases with thrombotic events as the main pathological basis are the leading cause of death in the population, and the incidence of both myocardial infarction and ischemic stroke is on the rise. The prevention and treatment of thrombotic diseases has become a public health problem and has attracted more and more attention from clinicians. As a cornerstone of antiplatelet therapy and prevention of cardiovascular diseases, aspirin is being used more and more widely. Antiplatelet drugs play an important role in the prevention and treatment of cardiovascular disease (CVD). As antiplatelet drugs represented by aspirin and clopidogrel are widely used in clinical practice, the gastrointestinal injury associated with these drugs has also become more and more concerned. The mechanisms of gastrointestinal injury caused by aspirin and clopidogrel are different, and the combination can further aggravate the injury, so it is urgent to treat the gastrointestinal adverse reactions caused by antiplatelet drugs in a reasonable manner and regulate them. First, how to avoid gastrointestinal injury? In order to minimize the gastrointestinal adverse reactions caused by antiplatelet drugs, the risk of gastrointestinal complications in patients with clear indications or long-term use should be fully evaluated, and the administration of antiplatelet drugs should be regulated. A history of GI disease (history of peptic ulcer or ulcer complications), age >65 years, high-dose aspirin, concomitant corticosteroids, combination of anticoagulants or non-steroidal anti-inflammatory drugs, Helicobacter pylori (Hp) infection, and comorbid other serious diseases are risk factors for gastrointestinal injury complicating antiplatelet therapy. Patients with a history of ulcers or ulcer complications should be tested for Hp and positive patients must be treated for Hp. Proton pump inhibitors (PPIs) should be given to patients with a history of gastrointestinal bleeding, peptic ulcers, combined antiplatelet therapy, or combined anticoagulants. If there are no such factors, but those who are >65 years old, use hormones, have loss of appetite or have symptoms such as abdominal discomfort, it is recommended to use effective gastric mucosal protective agents and add PPI if necessary. the benefits and risks of long-term prophylactic antiplatelet agents in low-risk patients with CVD are unknown so far, while the benefits of medication in medium- and high-risk patients and patients with coronary artery disease far outweigh the risks, so such patients should be on long-term regular medication. In addition, the long-term combination of antiplatelet agents should be minimized. Anticoagulant therapy aggravates gastrointestinal damage and significantly increases the risk of serious bleeding when combined with aspirin. Therefore, the combination of drugs must be clearly indicated and the drug dose should be adjusted to the minimum (≤100 mg/d for aspirin and 75 mg/d for clopidogrel), and the international normalized ratio (INR) should be controlled at 2.0-2.5. During long-term antiplatelet therapy, especially during the first 3 months, clinicians and patients should pay attention to observe and monitor patients for gastrointestinal discomfort and bleeding and other Adverse reactions and the presence of black stools or unexplained anemia should be noted for early detection of bleeding complications. It is recommended to review the fecal occult blood test every 1-3 months, and once bleeding occurs, the patient should immediately receive routine blood tests and active treatment. II. Is it necessary to stop the drug in case of bleeding? The decision to discontinue antiplatelet drugs after gastrointestinal complications should be based on individualized risk assessment of the patient’s risk of gastrointestinal complications and cardiovascular disease. In cases of dyspepsia only, antiplatelet agents may be discontinued with acid suppressants and gastric mucosal protective drugs. Patients with active bleeding often need to discontinue aspirin, but some patients (e.g., those with ACS, those with recent percutaneous coronary intervention, etc.) have an increased risk of cardiovascular events after discontinuation. When severe bleeding occurs in patients on multiple antiplatelet and anticoagulant drugs, the type and dose of drug should be reduced. When bleeding is life-threatening, all antithrombotic drugs may need to be discontinued. After adequate treatment of patients with bleeding complications, antiplatelet therapy may be restarted if there is no recurrence of bleeding within 3-7 days of discontinuation. A small study found that patients with gastrointestinal bleeding due to aspirin had significantly lower overall mortality in the continued drug group after gastroscopic hemostasis and PPI administration, but a slightly increased risk of bleeding, and a significant increase in cardiovascular events in the discontinuation group. The American College of Cardiology (ACC) guidelines for the management of non-ST-segment elevation myocardial infarction recommend that patients with coronary artery disease who are unable to tolerate aspirin because of gastrointestinal adverse effects may take clopidogrel instead, with the primary evidence derived from the Clopidogrel Versus Aspirin for the Prevention of Ischemic Events (CAPRIE) study. There was no significant difference in the incidence of hospitalization for gastrointestinal bleeding between the clopidogrel 75 mg group and the aspirin 325 mg group in this study. However, the clinically recommended long-term dose of aspirin is 75-150 mg, not 325 mg. Case-control studies have shown that adenosine diphosphate (ADP) receptor antagonists have a similar risk of causing upper gastrointestinal bleeding as aspirin. Two well-designed prospective studies also found that patients who developed ulcers after taking aspirin had a significantly lower rate of ulcer bleeding recurrence when given aspirin combined with a PPI compared with clopidogrel replacement after the ulcers had healed. Therefore, in patients at high risk of peptic ulcer or bleeding recurrence, clopidogrel substitution for aspirin is not recommended and aspirin combined with PPI should be given. III. How to view the interaction between antiplatelet drugs and PPI? The efficacy of H2 receptor antagonist is inferior to PPI but better than placebo, and the price of the drug is appropriate, so it can be used as an alternative drug when PPI cannot be used. The duration of PPI therapy is not clear. Since the incidence of gastrointestinal adverse reactions is highest during the first 3 months of aspirin administration, PPI should be used in combination with PPI during this period and thereafter can be managed on an individual basis. It is important to note that the antiplatelet efficacy of clopidogrel may be compromised by the combination of PPIs. Several retrospective studies have suggested an increase in coronary events in patients with coronary artery disease taking clopidogrel after long-term PPI combination therapy. A case-control study of patients with acute myocardial infarction showed a 27% higher relative risk of 90-day reinfarction in patients treated with clopidogrel combined with PPI after hospital discharge compared with those treated with clopidogrel alone. However, the interaction of different types of PPIs with clopidogrel varied, and an in vitro assay of ADP-induced platelet aggregation suggested that omeprazole affected the antiplatelet efficacy of clopidogrel, whereas pantoprazole and esomeprazole did not have these effects. Therefore, the indication and duration of prophylactic treatment with PPIs in patients with coronary artery disease receiving dual antiplatelet therapy remain to be studied.