The Association of Statin Dose and Mortality Risk Across Chronic Kidney Disease Stages in 665,858 United States Veterans

Rationale: Statin therapy is associated with lower mortality risk in both general and chronic kidney disease (CKD) populations. While statin therapy is recommended for CKD patients, the intensity of statin doses remains disputed. Thus, we examined the relationship of different statin doses with all-cause and cardiovascular (CVD) mortality across CKD stages. Methods: The cohort consists of 665,858 US Veterans with statin prescriptions between 2004-2014 who were followed until 2014. Statin intensity was categorized into low, moderate, and high dose based on ACC/AHA guidelines. Statin dosage and all-cause/CVD mortality associations were estimated using Cox proportional hazards models adjusting for comorbidities, labs, history of percutaneous coronary intervention and coronary artery bypass grafting across CKD stages. Results: Cohort mean age is 62+/-12 years with 6% females and 18% Blacks. Median [IQR] of eGFR is 79[64,93] mL/min/1.73m2 with 80% non-CKD. At baseline, 38%, 59%, and 3% patients were taking a low, moderate, and high dose of statin. A lower to null risk of all-cause and CVD mortality were found in low statin dose patients (ref: moderate statin dose) for all CKD stages. Furthermore, the association of low statin dose with all-cause mortality incrementally declined as CKD stages progressed. A null association of high statin dose with mortality risk was observed for all stages, with the exception of CKD stage 5/ESRD patients, where a 30% and 39% higher all-cause and CVD mortality risk were observed. [Figure] Conclusion: A low statin dose was associated with lower CVD mortality risk compared to a moderate dose in non-CKD patients. Yet, a high dose was associated with higher all-cause and CVD death risk in CKD stage5/ESRD patients. Statin therapy is known to improve patient outcomes; however, different intensities of statin should be applied when dealing with patients with different CKD stages as advanced stages of CKD may require adjustment in statin dosing.