Association of Opioid Prescription with Major Adverse Cardiovascular Events: Nationwide Cohort Study

<b>Background</b>: This study aimed to investigate the association between opioid use and the incidence of major adverse cardiovascular events (MACEs). <b>Methods</b>: This study included adult patients who had received oral or transdermal opioids in 2016. The control group comprised individuals who did not receive opioids in 2016 and was selected using a 1:1 stratified random sampling procedure. A MACE was defined as the occurrence of acute myocardial infarction, stroke, heart failure, or cardiovascular mortality. The primary endpoints were new MACEs and cardiovascular mortality, as evaluated from 1 January 2017 to 31 December 2021. <b>Results</b>: The study included 4,179,130 participants, of whom 1,882,945 (45.1%) were opioid users. After propensity score matching, 1,811,732 individuals (905,866 in each group) were included. Cox regression analysis revealed that the opioid user group had a 24% higher incidence of MACEs than the non-user group (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.23, 1.24; <i>p</i> < 0.001). Additionally, the opioid user group showed a 30% higher risk of cardiovascular mortality than the non-user group (HR: 1.30; 95% CI: 1.26, 1.35; <i>p</i> < 0.001). <b>Conclusions</b>: Opioid use was associated with an increased incidence of MACE and higher risk of cardiovascular mortality.