Association of Fenofibrate Therapy With Long-term Cardiovascular Risk in Statin-Treated Patients With Type 2 Diabetes

Abstract

clinicaltrials.gov Identifier: NCT00000620.

Evolving Role of Non‐Statin Therapy for the Management of Dyslipidemia and Cardiovascular Risk Reduction: Past, Present, and Future

“…Surprisingly, the combination of fenofibrate and simvastatin did not reduce ASCVD risk when compared to simvastatin monotherapy; however, the subgroup of patients with TG levels ≥204 mg/dl and HDL‐C levels ≤34 mg/dl had lower cardiovascular event rates with combination therapy compared to statin monotherapy . Similar results were observed in a 5‐year follow‐up study of the ACCORD‐Lipid trial . Based on this data, the American Diabetes Association recommends that clinicians consider adding fenofibrate to statin therapy in patients with elevated TG and low HDL‐C levels .…”

“…22 Similar results were observed in a 5-year follow-up study of the ACCORD-Lipid trial. 24 Based on this data, the American Diabetes Association recommends that clinicians consider adding fenofibrate to statin therapy in patients with elevated TG and low HDL-C levels. 25 Fibrates are not, however, a preferred non-statin in the Non-Statin ECDP given they primarily lower TG and not LDL-C. 11…”

Reverse GWAS: Using Genetics to Identify and Model Phenotypic Subtypes

“…There is no obvious FPR inflation as statin only has one other 176 significantly heterogeneous effect across other traits and K ∈ {3, 4, 5}. This is consistent 177 with statin interactions with age [38] and genetically predicted LDL [40] on T2D, and 178 also fenofibrate's interaction with lipid levels on cardiovascular risk [54]. By contrast, 179 large meta-analyses did not find inter-study statin heterogeneity [38,39].…”

“…Crucially, it remains calibrated even 53 when K = 1 (Figure 1b), so RGWAS discoveries validate the existence of subtypes. 54 Further, when K > 2 subtypes were simulated, MFMR with fixed K = 2 lost power but 55 remained calibrated ( Supplementary Figure 4). 56 Conversely, GMM is miscalibrated by an order of magnitude when K = 1, making it 57 unreliable for subtype validation (Figure 1b).…”

Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia

“…21 evidence that fenofibrate effectively reduced CVD in participants with high triglycerides (>204 mg/dL) and low HDL-C (<34 mg/dL) (HR, 0.73; 95% CI: 0.56-0.95) after an additional 5 years of follow-up (total, 9.7 years). 7 An intervention that increases HDL-C, however, is not necessarily accompanied by an enhancement of HDL function. There is an argument suggesting that HDL-C level per se does not represent the functionality of the HDL system.…”