Background:
Chronic kidney disease (CKD) patients have a higher cardiovascular (CV) disease and mortality risk, elevated triglycerides (TG), and decreased high density lipoproteins (HDL). Post-hoc analysis of trials examining use of fibrate (Fib) or niacin (Nia) therapy in lowering CV outcome risk have failed to show benefit in mild to moderate kidney disease. These analyses were criticized for their study design or small sample size. We sought to examine if Fib or Nia use is associated with lower mortality risk in US veterans across CKD stages.
Methods:
In a retrospective cohort analysis, we identified male veterans who initiated Fib or Nia, with a high TG ≥150 mg/dL or low HDL ≤40 mg/dL between 2004-2014, and matched them on CKD stage and TG and HDL levels to unexposed men. We examined the association of Fib or Nia use (ref: unexposed) with 12-month all-cause mortality risk across CKD stage strata using an adjusted Cox proportional hazards model. Propensity scores (PS) included baseline demographics, comorbidities and lab measures and high-dimensional propensity scores (HDPS) included over 100 covariates for each drug and stage analysis. PS and HDPS analyses included score adjustment and matching.
Results:
The cohort had a mean±SD age of 64±12 years, and 30% had CKD stage 3A and higher. There were 69,295 Fib, 87,727 Nia, and 114,411 unexposed patients, respectively. Patient characteristics were similar across drug groups within each CKD stage. With covariate adjustment, both Fib and Nia were associated with a lower death risk compared to unexposed men in lower CKD stages (Figure A and B). Among those with CKD stage 4/5, Fib and Nia were associated with a higher death risk (HR[95%CI]: 1.43[1.15, 1.78] and 1.17[0.97,1.40], respectively). Those on Fib or Nia and in end-stage renal disease had a null association with mortality. Associations were similar for each CKD stage in PS and HDPS analyses, yet Fib and Nia were no longer associated with a lower death risk for CKD stage 3A and 3B patients.
Conclusion:
Mortality associations of Fib and Nia among male veterans with high TG and low HDL varied across CKD stage, where CKD stage 4/5 patients had a higher mortality risk, even in PS and HDPS analyses. While covariate balance was met, further studies are needed to examine the mechanisms for this higher observed risk in late-stage CKD patients.
Chronic Kidney Disease and Mortality Risk: A Systematic Review