Background. Although cardiovascular disease and low high-density lipoprotein (HDL) cholesterol are common in people with renal insufficiency, data addressing the cardiovascular benefits of fibric acid derivatives in this population are sparse. We conducted a post hoc subgroup analysis of a randomized double-blind, placebo-controlled trial to determine whether gemfibrozil is effective and safe for secondary prevention of cardiovascular events in individuals with chronic renal insufficiency (CRI). Methods. Using an analysis plan that was developed a priori, we analyzed data from the Veterans' Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) study; a randomized trial of gemfibrozil versus placebo in 2531 men with established coronary disease, an HDL cholesterol level of 40 mg/dL (1.0 mmol/L) or less, and a low-density lipoprotein (LDL) cholesterol level of 140 mg/dL (3.6 mmol/L) or less. Of these, 1046 men had CRI as defined by creatinine clearance ≤75 mL/min using the Cockcroft-Gault equation, 99.8% of whom had either mild or moderate renal impairment (creatinine clearance 60-75 or 30-59.9 mL/min, respectively). Results. The incidence of the primary outcome (coronary death or nonfatal myocardial infarction) was lower in participants with CRI who received gemfibrozil compared to placebo [hazard ratio (HR) 0.73; 95% CI 0.56-0.96, P = 0.02). The cumulative incidence of the primary end point was reduced from 24.3% to 18.2%. In subjects with CRI, gemfibrozil also significantly reduced the risk of the combined outcome of coronary death, nonfatal myocardial infarction, or stroke (HR 0.74, 95% CI 0.58-0.95, P = 0.02), but not the need for coronary revascularization (HR 0.85, 95% CI 0.66-1.10, P = 0.21) or total mortality (HR 1.03, 95% CI 0.78-1.35, P = 0.85). The overall incidence of adverse effects was similar in individuals receiving gemfibrozil and placebo. However, the risk of sustained increases in serum creatinine was increased in gemfibrozil recipients compared with placebo (5.9 vs. 2.8%, P = 0.02). Conclusion. Gemfibrozil appears effective for secondary prevention of cardiovascular events in individuals with mild to moderate chronic renal insufficiency and HDL cholesterol of 40 mg/dL or less. However, the benefit and safety of gemfibrozil in people with more severe impairment of kidney function requires further study.
Bibliographical noteFunding Information:
The VA-HIT trial was an investigator-initiated study funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and by a supplemental grant from Parke-Davis. The pharmaceutical company was not involved in analyses or the decision to submit the manuscript for consideration. The authors had full access to all the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.
Dr. Robins has received honoraria and research support from Fournier Pharmaceuticals. The VA-HIT study was sponsored by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and by a supplemental grant from Parke-Davis. Dr. Tonelli was supported by a grant from the Alberta Heritage Foundation for Medical Research.
- Cardiovascular disease
- Kidney failure-chronic