Chemopreventive Effects of Concomitant or Individual Use of Statins, Aspirin, Metformin, and Angiotensin Drugs: A Study Using Claims Data of 23 Million Individuals

SIMPLE SUMMARY: Medications for chronic diseases, such as tatins, aspirin, metformin, and angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers, are studied for decades, and a vast body of previous research has suggested potential repurposing of these medications for cancer prevention. However, a limited number of studies have analyzed the effect of various combinations of these four medications/classes on cancer risks. This study, using large databases, aimed to comprehensively analyze the composite chemopreventive effects of all possible combinations of these four medications/classes. We found no synergistic effect of multiple use of these agents on cancer prevention in this study. Our results may provide information or inspiration for researchers or clinicians to conduct future research on combinations with cancer-preventive potential to further determine the optimal strategy for chemoprevention against cancer. ABSTRACT: Despite previous studies on statins, aspirin, metformin, and angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), little has been studied about all their possible combinations for chemoprevention against cancers. This study aimed to comprehensively analyze the composite chemopreventive effects of all the combinations. In this case-control study, health records were retrieved from claims databases of Taiwan’s Health and Welfare Data Science Center. Eligible cases were matched at a 1:4 ratio with controls for age and sex. Both cases and controls were categorized into 16 exposure groups based on medication use. A total of 601,733 cancer cases were identified. Cancer risks (denoted by adjusted odds ratio; 99% confidence interval) were found to be significantly decreased: overall risk of all cancers in statin-alone (0.864; 0.843, 0.886), aspirin-alone (0.949; 0.939, 0.958), and ACEIs/ARBs (0.982; 0.978, 0.985) users; prostate (0.924; 0.889, 0.962) and female breast (0.967; 0.936, 1.000) cancers in metformin-alone users; gastrointestinal, lung, and liver cancers in aspirin and/or ACEIs/ARBs users; and liver cancer (0.433; 0.398, 0.471) in statin users. In conclusion, the results found no synergistic effect of multiple use of these agents on cancer prevention. Use of two (statins and aspirin, statins and metformin, statins and ACEIs/ARBs, and aspirin and ACEIS/ARBs) showed chemopreventive effects in some combinations, while the use of four, in general, did not.