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Lipid intervention trials in diabetes
1Department of Medicine, Toronto Hospital (General Division), Ontario, Canada.
Insights
Lipid intervention trials often exclude diabetic patients. While some subgroup analyses show benefits in diabetes, new primary prevention studies are underway to confirm lipid reduction
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Most lipid intervention trials for coronary artery disease prevention exclude individuals with diabetes.
- Existing evidence for lipid reduction benefits in diabetes comes from post hoc analyses of trials like the Scandinavian Simvastatin Survival Study (4S) and the Cholesterol and Recurrent Events Trial (CARE).
Purpose of the Study:
- To review the current evidence for lipid intervention in diabetic populations.
- To highlight ongoing and upcoming clinical trials specifically designed to test the "lipid hypothesis" in diabetes.
Main Methods:
- Review of existing clinical trial data, focusing on subgroup analyses in diabetic patients.
- Description of ongoing and planned primary and secondary intervention trials in diabetes.
Main Results:
- Post hoc analyses of gemfibrozil (Helsinki Heart Study) showed a trend towards reduced coronary events in diabetics, but lacked statistical significance.
- Secondary intervention trials (4S, CARE) using statins demonstrated significant reductions in coronary events in diabetic subgroups, though these were hypercholesterolemic populations.
Conclusions:
- Existing evidence for lipid reduction in diabetes is limited and requires cautious interpretation due to post hoc nature and population characteristics.
- Several large-scale primary prevention trials (FIELD, CARDS, LDS) and an angiographic study (DAIS) are ongoing to provide definitive evidence on lipid management in diabetes.
Abstract:
Most clinical trials of lipid intervention and coronary artery disease prevention have been conducted in study populations that exclude diabetic individuals. Three trials have conducted post hoc analyses of their diabetic subgroups. One of these was a primary intervention trial with gemfibrozil (Helsinki Heart Study). Although this trial found a reduction in coronary events, the numbers were too small to reach significance. The two other trials (the Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events Trial [CARE]) were secondary intervention trials conducted with hydroxymethylglutaryl-CoA reductase inhibitors, simvastatin, and pravastatin. Both of these trials found a reduction in coronary events. Although these two trials present the strongest evidence in support of the clinical benefits of lipid reduction in diabetes, they must be interpreted with caution. They are post hoc subgroup analyses, they looked at mainly hypercholesterolemic populations, and they are secondary intervention studies. Four studies aimed at testing the "lipid hypothesis" specifically in diabetes are currently under way. Three of these studies (Fenofibrate Intervention and Event Lowering in Diabetes [FIELD], Collaborative Atorvastatin Diabetes Study [CARDS], and Lipids in Diabetes Study [LDS]) are primary prevention trials, with clinical events as the primary end point. FIELD uses micronized fenofibrate, CARDS uses atorvastatin, and LDS uses both micronized fenofibrate and cerivastatin alone or in combination. These trials are in the early stages of starting or recruiting. One study (Diabetes Atherosclerosis Intervention Study [DAIS]) using micronized fenofibrate is nearing completion. It is an angiographic study that combines those with and without preexisting clinical coronary disease.