"Fenofibrate and Simvastatin Not Beneficial in Reducing Cardiovascular Events in Patients with Type 2 Diabetes".The New England Journal of Medicine. 2010.PubMed•Full text•PDF

Contents

1Clinical Question
2Bottom Line
3Major Points
4Guidelines
5Design
6Population
6.1Inclusion Criteria
6.2Exclusion Criteria
6.3Baseline Characteristics
7Interventions
8Outcomes
8.1Primary Outcome
8.2Secondary Outcomes
9Criticisms
10Funding
11Further Reading

Clinical Question

In high-risk patients with type 2 diabetes mellitus already on statin therapy, does additional fenofibrate therapy reduce the risk of cardiovascular events?

Bottom Line

In high-risk patients with type 2 diabetes on simvastatin therapy, addition of fenofibrate did not reduce cardiovascular events compared to placebo. Routine use of this combination therapy is not supported for reducing cardiovascular risk in the majority of patients with type 2 diabetes.

Major Points

Type 2 diabetes patients are at an elevated risk for cardiovascular disease, partly due to dyslipidemia characterized by elevated triglycerides, low HDL cholesterol, and small, dense LDL particles. This study tested whether the addition of fenofibrate to statin therapy in such patients would further reduce cardiovascular events.

Guidelines

Modern guidelines do not currently support the use of combination fibrate-statin therapy over statin therapy alone for the majority of patients with type 2 diabetes at high cardiovascular risk.

Design

Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial.

Population

Patients with type 2 diabetes at high risk for cardiovascular disease, on statin therapy.

Inclusion Criteria
LDL cholesterol 60-180 mg/dL, low HDL cholesterol, triglycerides <750 mg/dL without lipid therapy or <400 mg/dL with lipid therapy.

Exclusion Criteria
Not provided.

Baseline Characteristics
Mean age was 62 years, 31% female, 37% with history of cardiovascular event.

Interventions

Patients on open-label simvastatin were randomly assigned to either fenofibrate or placebo on top of their statin therapy.

Outcomes

Primary Outcome
First occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.

Secondary Outcomes
Rates of death, secondary efficacy endpoints like revascularization and hospitalization for congestive heart failure.

Criticisms

Despite broad inclusion criteria and adequate power, no significant benefit was found. Selection criteria and event rates suggest possible benefit for certain subgroups with severe dyslipidemia.

Funding

National Heart, Lung, and Blood Institute, other NIH institutes, CDC, and General Clinical Research Centers, with study medications donated by various pharmaceutical companies.

Further Reading

For further information on this study, please refer to the full text article available at NEJM.org.