Association of Non‐Cytochrome P450 3A4‐Metabolized Statins Versus Atorvastatin With Major Adverse Cardiovascular Events in Patients With Cancer Receiving Tyrosine Kinase Inhibitors: A Propensity Score–Matched Target Trial Emulation
4 affiliations
- 1Tri‐Service General Hospital, National Defense Medical University
- 2Universe Eye Center
- 3Changhua Christian Hospital
- 4Chi Mei Medical Center
Abstract
Background Tyrosine kinase inhibitors (TKIs) often undergo CYP3A4 (cytochrome P450 3A4) metabolism. Atorvastatin is a CYP3A4 substrate, whereas rosuvastatin and pitavastatin largely bypass this pathway. We evaluated whether statin choice was associated with major adverse cardiovascular events in TKI‐treated patients with cancer. Methods Using TriNetX, we conducted an active‐comparator, new‐user target trial emulation among adults with cancer receiving their first TKI. The index date was the first statin dispensation; outcome ascertainment began on Day 30 and continued up to 3 years. Separate 1:1 propensity score‐matched comparisons included rosuvastatin versus atorvastatin (primary; 2215 per group), pitavastatin comparisons, and a pooled non‐CYP3A4 statin comparison. Results Among 10 843 eligible patients (mean age, 66.7 years; 60.7% male), rosuvastatin was associated with a lower major adverse cardiovascular events rate than atorvastatin (624 versus 769 events; hazard ratio [HR], 0.84 [95% CI, 0.76–0.93]). The proportional‐hazards assumption was violated ( P =0.042), so the HR was interpreted as a time‐averaged association. The pooled comparison was concordant (HR, 0.87 [95% CI, 0.78–0.96]). The early‐persistence Day‐180 estimate was imprecise (HR, 0.90 [95% CI, 0.73–1.09]). Conclusions Rosuvastatin use was associated with lower major adverse cardiovascular events than atorvastatin in TKI‐treated patients with cancer. This observational finding is compatible with, but does not establish, a CYP3A4‐mediated interaction. Residual confounding, nonaligned TKI and statin timing in part of the primary cohort, and lack of individual‐level event‐time data require prospective confirmation.
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BibTeX
@article{liao2026association,
title = {{Association of Non‐Cytochrome P450 3A4‐Metabolized Statins Versus Atorvastatin With Major Adverse Cardiovascular Events in Patients With Cancer Receiving Tyrosine Kinase Inhibitors: A Propensity Score–Matched Target Trial Emulation}},
author = {Jing‐Huan Liao and Wei‐Cheng Chang and Hong‐Jie Jhou and Hsin‐Yu Chen and Po‐Huang Chen and Cho‐Hao Lee},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.053141},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.053141},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Association of Non‐Cytochrome P450 3A4‐Metabolized Statins Versus Atorvastatin With Major Adverse Cardiovascular Events in Patients With Cancer Receiving Tyrosine Kinase Inhibitors: A Propensity Score–Matched Target Trial Emulation
AU - Jing‐Huan Liao
AU - Wei‐Cheng Chang
AU - Hong‐Jie Jhou
AU - Hsin‐Yu Chen
AU - Po‐Huang Chen
AU - Cho‐Hao Lee
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.053141
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.053141
AB - Background Tyrosine kinase inhibitors (TKIs) often undergo CYP3A4 (cytochrome P450 3A4) metabolism. Atorvastatin is a CYP3A4 substrate, whereas rosuvastatin and pitavastatin largely bypass this pathway. We evaluated whether statin choice was associated with major adverse cardiovascular events in TKI‐treated patients with cancer. Methods Using TriNetX, we conducted an active‐comparator, new‐user target trial emulation among adults with cancer receiving their first TKI. The index date was the first statin dispensation; outcome ascertainment began on Day 30 and continued up to 3 years. Separate 1:1 propensity score‐matched comparisons included rosuvastatin versus atorvastatin (primary; 2215 per group), pitavastatin comparisons, and a pooled non‐CYP3A4 statin comparison. Results Among 10 843 eligible patients (mean age, 66.7 years; 60.7% male), rosuvastatin was associated with a lower major adverse cardiovascular events rate than atorvastatin (624 versus 769 events; hazard ratio [HR], 0.84 [95% CI, 0.76–0.93]). The proportional‐hazards assumption was violated ( P =0.042), so the HR was interpreted as a time‐averaged association. The pooled comparison was concordant (HR, 0.87 [95% CI, 0.78–0.96]). The early‐persistence Day‐180 estimate was imprecise (HR, 0.90 [95% CI, 0.73–1.09]). Conclusions Rosuvastatin use was associated with lower major adverse cardiovascular events than atorvastatin in TKI‐treated patients with cancer. This observational finding is compatible with, but does not establish, a CYP3A4‐mediated interaction. Residual confounding, nonaligned TKI and statin timing in part of the primary cohort, and lack of individual‐level event‐time data require prospective confirmation.
SN - 2047-9980
ER -