Coronary atherosclerosis can lead to severe consequences such as coronary artery stenosis, myocardial ischemia, and myocardial infarction. When unstable plaques rupture, platelets accumulate and adhere to the rupture site, forming fibrin and activating the coagulation system, which results in thrombosis (Wu et al., 2019). Coronary artery bypass grafting (CABG) is a highly effective treatment for coronary heart disease, as it establishes collateral circulation to improve myocardial ischemia and hypoxia (Doenst et al., 2019). However, restenosis of the graft vessel can occur post-CABG, leading to the failure of the re-established collateral circulation, recurring myocardial ischemia, and hypoxia. This increases the likelihood of secondary revascularization and long-term patient mortality (Zhao et al., 2018). Platelet activation and aggregation are crucial in the development of atherothrombosis, making antiplatelet therapy vital in treating coronary heart disease (Davì and Patrono, 2007; Gaudino et al., 2017).

Aspirin is a widely used antiplatelet drug that reduces the synthesis and release of thromboxane A2, inhibiting platelet aggregation and thrombosis (Johnston et al., 2019). However, long-term use of aspirin is associated with a high incidence of gastrointestinal injury and bleeding, leading to poor patient tolerance. Consequently, guidelines and textbooks recommend indobufen as an alternative for aspirin-intolerant patients who are at high risk of bleeding and gastric ulcers (Yong Huo et al., 2021; Specialty Committee on Prevention and Treatment of Thrombosis of Chinese College of Cardiovascular Physicians et al., 2019). While aspirin’s role in preventing and treating cardiovascular and cerebrovascular diseases is well-supported by substantial evidence, research evidence for indobufen remains relatively limited. This study compared the safety and efficacy of indobufen and aspirin following CABG, aiming to provide clinical references for the use of indobufen and to inform future large-scale multicenter prospective studies.

The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, revascularization due to acute coronary syndrome, and major bleeding complications during the follow-up period (8–18months). Major bleeding was defined as Bleeding Academic Research Consortium (BARC) type 3 or higher bleeding. The individual components of the primary endpoint, revascularization, and minor gastrointestinal complications were analyzed as secondary endpoints at 18 months. Interim analysis was not planned or conducted during the follow-up duration. Post-hoc secondary composite endpoints included thrombotic composite endpoint (cardiac death, non-fatal myocardial infarction, ischemic stroke, revascularization, definite or probable stent thrombosis) and any bleeding (BARC type ≥2 bleeding).

A total of 39 patients with coronary heart disease undergoing CABG were enrolled (the selection process is shown in Figure 1). The baseline characteristics of the total population are shown in Table 1. There were 19 patients in the indobufen group, including 4 females (21.05%), aged 63.84 ± 7.99 years. There were 20 patients in the aspirin group, including 4 females (20%), aged 64.60 ± 6.72 years. The two groups were well-balanced for demographic, clinical, and procedural characteristics and non-trial-related medications. There were no significant differences in gender, age, BMI, hypertension, diabetes, hyperlipidemia, history of cerebral infarction, history of myocardial infarction, and peripheral arterial plaque between the two groups (p > 0.05).

During the 8–18 months follow-up, the primary endpoint occurred in 5 (25%) patients who received aspirin and in none who received indobufen (p = 0.02), indicating an absolute risk reduction. The incidences of the individual components of the primary endpoint and other secondary endpoints are shown in Table 2. During the 8–18 months follow-up, no patients died in either group. The incidence of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were lower in the indobufen group than in the aspirin group. Regarding the primary endpoint, the beneficial effect of indobufen compared with aspirin was generally consistent across all prespecified subgroups (Table 2).

The secondary safety endpoint of bleeding events and gastrointestinal reaction occurred in 3 (15.79%) patients in the indobufen group and 14 (70%) patients in the aspirin group (p = 0.01). Total bleeding (BARC type ≥2) occurred in three patients (15.79%) in the indobufen group and 11 patients (55%) in the aspirin group (p = 0.011). There were 3 cases of gastrointestinal bleeding and a case of incision bleeding as major bleeding and 7 cases of hidden blood loss as minor bleeding in the aspirin group. The incidence of bleeding events, especially major bleeding events, was significantly lower in the indobufen group. Gastrointestinal complications occurred in three patients (15%) in the aspirin group and no patients in the indobufen group (p = 0.079), suggesting a safety advantage for the indobufen group.

Comparing bleeding and coagulation-related indicators and postoperative hospital stay, there was no significant difference in Hb, D-dimer levels and postoperative hospital stay between the indobufen group and the aspirin group (p > 0.05). However, PLT and APTT in the indobufen group were significantly lower than in the aspirin group (p = 0.001 and p = 0.018, respectively).

Considering that patients after CABG generally need to take dual antiplatelet drugs for 1 year and continue long-term oral antiplatelet drugs after stablization, the cost of antiplatelet drugs in both groups was calculated. Patients in the indobufen group received 100 mg bid daily, with the unit price of indobufen being 6.95 yuan/100 mg. The unit price of aspirin was 0.50 yuan/100 mg. Thus, the average daily cost of antiplatelet drugs in the indobufen group was 27.8 times higher than in the aspirin group. Long-term use of indobufen is expensive, and from a pharmacoeconomics perspective, indobufen is less cost-effective than aspirin.

Coronary heart disease is a leading cause of mortality with an increasing incidence, particularly among younger patients (Mahjoob et al., 2018). Platelet activation and aggregation are critical in atherosclerotic thrombosis development. While aspirin and clopidogrel combination therapy is common, some patients experience severe gastrointestinal reactions and poor tolerance to aspirin. Indobufen, a novel platelet aggregation inhibitor, offers minimal gastrointestinal effects (Yang et al., 2017; Chen et al., 2022; Wu et al., 2023; Lu and Xu, 2021).

The findings of this study provide valuable insights into the safety and efficacy of indobufen compared to aspirin in patients undergoing CABG. The results demonstrate a significant reduction in primary and secondary endpoint events, particularly bleeding complications, with indobufen, highlighting its potential as a safer alternative to aspirin in this patient population.

Our study revealed a notable difference in the occurrence of the primary composite endpoint between the indobufen and aspirin groups. The absence of primary endpoint events in the indobufen group compared to a 25% occurrence in the aspirin group underscores the effectiveness of indobufen in preventing adverse cardiovascular events post-CABG. This finding aligns with previous research suggesting that indobufen’s antiplatelet activity, while comparable to that of aspirin, may confer additional benefits in specific clinical scenarios due to its distinct pharmacological profile (Johnston et al., 2019).

The reduced incidence of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events in the indobufen group further supports its efficacy. These outcomes are particularly relevant given the critical role of platelet activation and aggregation in the pathogenesis of atherothrombosis and subsequent cardiovascular events (Davì and Patrono, 2007; Gaudino et al., 2017). The results suggest that indobufen may offer a more robust protective effect against recurrent ischemic events in post-CABG patients.

One of the most significant findings of our study is the markedly lower incidence of bleeding events in the indobufen group. The secondary safety endpoint of bleeding events and gastrointestinal reactions was significantly lower in the indobufen group (15.79%) compared to the aspirin group (70%), with a p-value of 0.01. Major bleeding events, defined as BARC type ≥3, were notably fewer in the indobufen group. This finding is crucial because bleeding complications can significantly impact patient outcomes, leading to increased morbidity and mortality and necessitating additional medical interventions (CotpatCmd et al., 2018).

The lower incidence of gastrointestinal complications in the indobufen group, although not statistically significant (p = 0.079), indicates a trend toward better gastrointestinal tolerability compared to aspirin. This is an important consideration for long-term antiplatelet therapy, where gastrointestinal side effects are a common cause of medication discontinuation and non-compliance.

The study also assessed bleeding and coagulation-related indicators, such as Hb, D-dimer levels, and APTT. While there were no significant differences in Hb and D-dimer levels or postoperative hospital stay between the groups, PLT and APTT were significantly lower in the indobufen group. This finding suggests a more favorable coagulation profile with indobufen, potentially contributing to its lower bleeding risk.

Despite the clinical advantages of indobufen, the economic analysis highlights a significant drawback. The daily cost of indobufen therapy was substantially higher than that of aspirin, making long-term use less cost-effective. Given the necessity for prolonged antiplatelet therapy post-CABG, the high cost of indobufen could be a limiting factor for its widespread adoption, particularly in resource-limited settings. While indobufen demonstrated a superior safety profile compared to aspirin, its significantly higher cost—27.8 times more expensive—raises concerns about its cost-effectiveness for long-term use, especially in resource-limited settings. The economic burden of indobufen could restrict its accessibility, despite its clinical benefits. Future studies should include comprehensive pharmacoeconomic analyses to evaluate the cost-effectiveness of indobufen relative to other antiplatelet therapies.

This study demonstrates that indobufen provides a comparable antiplatelet effect to aspirin, with a significant reduction in gastrointestinal reactions and bleeding events. Indobufen’s high selectivity and reversible receptor binding make it particularly suitable for aspirin-intolerant patients with high bleeding risk and gastric ulcers. Despite the promising results, this retrospective study’s limited sample size may introduce bias, and the shorter history of indobufen usage means its evidence base is less robust compared to aspirin.

Aspirin remains the preferred drug for primary and secondary prevention of cardiovascular and cerebrovascular diseases due to its established efficacy, availability, and cost-effectiveness. However, indobufen and other antiplatelet agents should be considered for patients who are intolerant to or contraindicated for aspirin. Further large-scale clinical trials are needed to validate these findings and to determine whether indobufen can replace aspirin as the first-choice antiplatelet therapy post-CABG.