Does Extended Use of Clopidogrel-Based Dual Anti-Platelet Therapy Increase the Risk of Gastrointestinal Bleeding?

Background: Clopidogrel-based dual anti-platelet therapy (CDAPT) has shown significant benefits in the management of coronary artery disease (CAD), up to 1-year duration. Gastrointestinal bleeding (GIB) is one of the limiting factors for prolonged use of CDAPT. Methods: We identified all patients taking CDAPT from our ambulatory clinics. Demographic, clinical, laboratory and pharmacological data were abstracted. American Heart Association (AHA) guidelines were used to determine the duration of CDAPT therapy. The study population was divided into two groups based on the duration of therapy. Individuals who received CDAPT more than 12 months were deemed as extended use. Results: A total of 351 patients with CAD were taking CDAPT. Majority of patients (276/351, 79%) were taking CDAPT beyond 1 year. There were no differences in baseline characteristics between the two groups. There was no significant difference in the incidence of GIB between the two groups. However, in subgroup analysis, there was a significant difference in the incidence of GIB in men. Men who were taking CDAPT beyond 12 months had almost three times higher incidence of GIB compared to those who were taking less than 12 months (25% vs. 8%, P = 0.04). The excess GIB in men prevailed despite adjusting for non-steroidal anti-inflammatory drugs (NSAIDs) or direct oral anticoagulant (DOAC) use. Conclusions: We found that a majority of patients were taking CDAPT beyond the recommended duration. We observed that men taking CDAPT for an extended duration had a three times higher incidence of GIB. It would be reasonable for physicians to be aware of the higher risk of GIB in men and carefully assess the risks and benefits of extended use of CDAPT.