Background: Statins, among the most widely prescribed medications worldwide, inhibit the mevalonate pathway and are well-established in cardiovascular disease prevention. Increasing interest has focused on their potential anticancer effects through interference with metabolic processes essential to tumor growth. While prior studies have examined associations between statin use and cancer risk, findings have been variable, and their role in hematologic malignancies remains unclear. This study investigates the association between statin use and the risk of developing acute myeloid leukemia (AML) in patients with ischemic heart disease or hyperlipidemia.

Methods: Using TriNetX, a global federated health research network encompassing 152 healthcare organizations, we conducted a retrospective observational study comparing AML incidence among statin users and non-users. Adults with a history of ischemic heart disease or hyperlipidemia were identified and separated into two cohorts based on statin exposure: Cohort 1 included individuals with no prior statin use, and Cohort 2 included those who had been prescribed statins. Patients with a prior diagnosis of AML, a history of other malignancies, or previous exposure to chemotherapy or radiation were excluded. Propensity score matching (PSM) was applied based on age, sex, race, and ethnicity, resulting in two balanced cohorts (n=4,837,765 each). The primary outcome was incident AML; secondary analysis assessed overall survival. Risk ratios, hazard ratios, and Kaplan-Meier survival curves were generated to compare time-to-event outcomes between groups.

Results: Before matching, Cohort 1 (no statin use) included 8,760,690 patients, and Cohort 2 (statin use) included 4,925,828 patients. After propensity score matching (PSM) on age, sex, race, and ethnicity, both cohorts included 4,837,765 patients with well-balanced baseline characteristics. The mean age was 63.6 vs. 63.5 years, the proportion of male patients was 52.1% vs. 52.5%, and standardized differences for racial and ethnic distributions were all < 0.04. The incidence of AML was higher in the non-statin cohort (27.1 per 100,000) compared to the statin cohort (17.7 per 100,000), corresponding to 1,312 vs. 858 cases and a risk ratio of 1.53 (95% CI: 1.40-1.67; p<0.001). The hazard ratio for AML was 1.60 (95% CI: 1.47-1.75), reflecting a 60% increased risk in non-statin users. Kaplan-Meier analysis also demonstrated a statistically significant survival advantage in the statin group (99.91% vs. 99.82%; p<0.001).

Conclusion: In this large, real-world cohort of nearly 10 million patients, statin use was associated with a significant reduction in AML risk. Given statins' favorable safety profile and widespread use, even modest reductions in AML risk may carry important population-level implications. These findings support the need for further investigation through mechanistic studies and prospective trials to better understand whether statins may have a role in leukemia prevention.

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2025
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