Clopidogrel, an ADP ‐ P2Y12 Receptor Antagonist, Is Associated With Lower Opioid Consumption and a Reduced Incidence of Delirium in Cancer Patients Receiving Chemotherapy: A Nationwide Retrospective Cohort Study in Japan

BACKGROUND: P2Y12 receptor activation stimulates spinal microglia and exacerbates pain. However, whether clopidogrel, a P2Y12 receptor antagonist, has analgesic properties remains unclear. This study aimed to evaluate the association between clopidogrel use and opioid consumption in cancer patients receiving chemotherapy. METHODS: We identified cancer patients receiving inpatient chemotherapy between January 2019 and December 2020 using the Diagnosis Procedure Combination database, a Japanese national inpatient database. Propensity score matching was conducted between clopidogrel and aspirin users. The primary outcome was opioid consumption during hospitalization. The secondary outcomes included analgesic use (opioids, acetaminophen, nonsteroidal anti-inflammatory drugs, and gabapentinoids) and hyperactive delirium. RESULTS: Among 71 554 eligible patients (male, 73%; mean age, 73.7 years), 25.3% were administered clopidogrel and 74.7% were administered aspirin. Propensity score matching included 18 135 and 36 270 patients in the clopidogrel and aspirin groups, respectively. The median daily opioid consumption in morphine milligram equivalent was significantly lower in the clopidogrel group than in the aspirin group (16.4 mg/day vs. 21.4 mg/day; p < 0.001). The analgesic use was significantly lower in the clopidogrel group for opioids (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.78-0.88; p < 0.001), acetaminophen (OR, 0.91; 95% CI, 0.88-0.95; p < 0.001), and nonsteroidal anti-inflammatory drugs (OR, 0.83; 95% CI, 0.80-0.87; p < 0.001). Moreover, the occurrence of hyperactive delirium was significantly lower in the clopidogrel group (OR, 0.80; 95% CI, 0.69-0.92; p = 0.002). CONCLUSIONS: Clopidogrel may have an analgesic effect in cancer patients receiving chemotherapy.