A Drug-Environment Interaction Between PM_{2 .5} Concentration and Corticosteroid Use on Cardiovascular and...

Few studies have investigated the interaction between drug-environment despite the plausibility and concern. We sought to explore the synergistic effects of corticosteroids and PM_2.5 on cardiovascular and thromboembolic events in high-risk older adults in Taiwan.

To assess the synergistic effect of corticosteroid use and PM_2.5 exposure on cardiovascular and thromboembolic events and all cause mortality among elderly individuals in Taiwan.

We conducted a retrospective cohort study using the Taiwan National Health Insurance database from 2009 to 2019. We included patients aged 65 years or older and at high risk for cardiovascular and thromboembolic events. Exposures included corticosteroid therapy and seasonal mean PM_2.5. Primary outcomes included myocardial infarction or acute coronary syndrome, ischemic stroke or transient ischemic attack, heart failure, venous thromboembolism, atrial fibrillation, and all-cause mortality. We then fitted history-adjusted marginal structural Cox proportional hazard models to investigate both the independent and synergistic effects of PM_2.5 and corticosteroid use on the CTE outcomes. We measured whether there was a sufficient cause interaction between PM_2.5 and corticosteroids using estimates of relative excess risk due to interaction (RERI).

The cohort included 373 402 participants, with average age at index date 73.6 ± 7.2 years; 57.7% of cohort members were female. During the study period, 1 614 331 (43.2%) participants had at least one corticosteroid prescription. The average PM_2.5 concentration was 28.3 ± 17.4 μg/m³. Increasing PM_2.5 from 15 to 20 μg/m³ resulted in significantly increased excess risk due to interaction (RERI [95% CI]) for all-cause mortality (3.1% [0.27%, 5.9%]).

A synergistic effect between seasonal PM_2.5 exposure and corticosteroid use was found on all-cause mortality in elderly patients at high risk for cardiovascular and thromboembolic events.