Background: Acute coronary syndrome (ACS) carries significant risks of recurrent cardiovascular (CV) events and bleeding complications. In particular, Asian patients have higher rates of bleeding complications due to genetic and physiological factors. Bleeding complications are associated with an increased risk of subsequent thrombotic events, and the impact of such complications on long-term outcomes must therefore be investigated. This study compared long-term outcomes and clinical characteristics between ACS patients who experienced a single ACS event and those who experienced multiple CV events. Methods: Utilizing data from Taiwan's National Health Insurance Research Database, this retrospective cohort study categorized patients into single-event and multiple-event groups based on the occurrence of major adverse CV events within 2 years after the index ACS event. In this cohort study, 28,535 patients were included. After matching by age, sex, and the interval between the first and second CV events at a 1:2 ratio, 8,720 patients were included in the multiple-event group and 17,368 in the single-event group. Results: The multiple-event group had higher rates of comorbidities, including hypertension, prior coronary artery disease, heart failure, stroke, and chronic kidney disease. Over a 5-year period, the multiple-event group exhibited higher all-cause mortality (34.1% vs. 24.6%, p < 0.0001) and CV mortality (11.4% vs. 6.2%, p < 0.0001) than the single-event group. The rates of major bleeding events (7.8% vs. 1.6%, p < 0.0001) and minor bleeding events (34.4% vs. 7.2%, p < 0.0001) were also higher in the multiple-event group than in the single-event group. Compared with the single-event group, which showed a significant reduction in major bleeding events 1 month after the index ACS event, the multiple-event group continued to have a higher rate of major bleeding events within 3 months following the index ACS event. In the multiple-event group, patients who experienced a major bleeding event had an earlier onset of subsequent CV events than patients who did not experience a major bleeding event. Specifically, every 1-day earlier occurrence of major bleeding was associated with a 1.0044-day earlier occurrence of a subsequent CV event. Conclusion: ACS patients with multiple CV events have higher rates of all-cause mortality, CV mortality, and major bleeding than ACS patients with a single CV event. However, major bleeding may be associated with the risk of subsequent CV events, highlighting the importance of implementing a tailored antiplatelet strategy in Asian populations.

The authors have declared no competing interest.

This work was supported by AstraZeneca Taiwan Ltd. under the project code A-112-004-T. The study titled "REal-world Characteristics and outcome events in patients Underwent more than Once major cardiovascular events in 2 years (RECURRENT)" was led by Dr. Chien-Yi Hsu. The funders provided support for study design, data collection, statistical analysis, and manuscript preparation. The authors declare that no additional payments or services were received from any other third party related to the work presented in this manuscript.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Joint Institutional Review Board of Taipei Medical University (TMU-JIRB No. 202305022). Since the data from the National Health Insurance Research Database (NHIRD) is anonymized, the requirement for informed consent was waived.

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The data used in this study were obtained from the Taiwan National Health Insurance Research Database (NHIRD), which is managed by the National Health Research Institutes (NHRI). Access to the NHIRD is restricted and requires permission from the NHRI. Researchers who meet the criteria for access to confidential data can apply for access at the NHRI?s website (http://nhird.nhri.org.tw).