Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study

Taek-Geun Kwon,Seung Hwan Han,Sang-Hyun Kim,Young Joon Hong,Jang-Ho Bae,Albert Youngwoo Jang,Sang Wook Kim,Sung Yun Lee

doi:10.1186/s13063-020-04291-5

Abstract

BackgroundDespite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate.Methods/designThe STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions.DiscussionThe STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD.Trial registrationClinicalTrials.gov, NCT02232360. Registered 9 February 2014.https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2

Highlights

Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate
Percutaneous coronary intervention and optimal low-density lipoprotein cholesterol (LDLc)lowering statin therapy have substantially reduced recurrent CV events in acute coronary syndrome (ACS), two-thirds of the CV disease risk remains [2,3,4,5,6,7]; this highlights the need to redirect the current CV reduction algorithms to focus beyond LDLc reduction and the use of statins [7, 8]
We seek to determine the additive impact of fenofibrate versus optimal statin therapy on non-culprit lesions in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease using well-defined virtual histology-intravascular ultrasound (VH-intravascular ultrasound (IVUS)) criteria

Summary

Introduction

Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate. Percutaneous coronary intervention and optimal low-density lipoprotein cholesterol (LDLc)lowering statin therapy have substantially reduced recurrent CV events in ACS, two-thirds of the CV disease risk remains [2,3,4,5,6,7]; this highlights the need to redirect the current CV reduction algorithms to focus beyond LDLc reduction and the use of statins [7, 8]. A meta-analysis of fibrates on CV outcomes confirmed a significant reduction in CV disease risk without an increase in drug-related adverse events [12] These data suggest that statin and fenofibrate combination therapy is a potential alternative to statin alone in CAD patients with high levels of non-HDLc. Angiographically, mild atherosclerotic plaques account for 50% of recurrent CV events, further bringing non-culprit vessels into focus as a useful surrogate marker for future CV events [5]. We seek to determine the additive impact of fenofibrate versus optimal statin therapy on non-culprit lesions in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease using well-defined VH-IVUS criteria

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