Statin Use and Major Adverse Cardiac Events among High Cardiac Risk Patients with Lung Cancer Receiving Radiotherapy

Abstract

Statin use is recommended in patients with high Framingham risk or established coronary heart disease (CHD). Patients with lung cancer have a high prevalence of pre-existing CHD and face excess cardiac risk following thoracic radiotherapy (RT). We sought to characterize statin use by cardiac risk in a large cohort of patients with locally advanced non-small cell lung cancer (NSCLC) treated with RT. Retrospective analysis of 748 locally advanced NSCLC patients treated with thoracic RT. Patients were stratified by 10-year Framingham risk. High cardiac risk was defined as either high (≥20%) Framingham risk or pre-existing CHD or CHD risk equivalent. The cumulative incidence of major adverse cardiac events (MACE; unstable angina, heart failure, myocardial infarction [MI], coronary revascularization, and cardiac death) was estimated and Fine and Gray regressions were performed (non-cardiac death as a competing risk). The median follow-up was 20 months overall and 48 months in patients alive. Among CHD-negative patients (64.2%), 27.9% were low Framingham risk, 25.0% moderate and 47.1% high risk. At the time of RT, statin use by Framingham risk group (low, moderate, or high) or known CHD was 15.7%, 25.8%, 37.2%, and 63.1%, respectively. Among all high cardiac risk patients (66%, n = 496), only 51.2% were on a statin at the time of RT. High cardiac risk patients on statins (compared to no statin) were more likely to have a history of hypertension (73.3% vs. 51.4%, P<.001), hyperlipidemia (83.4% vs. 29.2%, P<.001), diabetes (28.1% vs. 11.5%, P<.001), former smoking (62.1% vs. 49.4%, P = .017), peripheral vascular disease (17.1 vs. 7.4%, P = .001), stroke (4.4% vs. 1.2%, P = .032), coronary artery disease (52.2% vs. 32.5%, P<.001), MI (49.6% vs. 26.0%, P = .001), and congestive heart failure (17.8% vs. 6.6%, P<.001), with no significant difference in age, sex, performance status, cancer stage, chemotherapy use, RT prescription dose, or cardiac or coronary RT dose exposure (P>.05). Statin use was associated with increased risk of MACE in high cardiac risk patients on univariable analysis (hazard ratio [HR] 1.76; 95% CI: 1.06-2.90; P = .027) with 2-year MACE estimates of 10.9% vs. 4.5%, but not when adjusted for known cardiac prognostic factors (P = 0.4). Only half of statin-eligible high cardiac risk patients with locally advanced NSCLC are on a statin at the time of RT. Even among high cardiac risk patients, those on statins harbored significantly more cardiac risk factors than those not on statins, suggesting only those of highest cardiac risk are on anti-lipid therapy at the time of RT. These results highlight that NSCLC patients represent a distinctly high cardiac risk population due to elevated baseline risk factors and cardiac radiation exposure with an unmet need for improved cardiac risk reduction, including optimization of medical therapy.