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What does the future hold for diabetic dyslipidaemia?
1Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63141, USA.
Abstract:
Preliminary evidence from trials with the HMG-CoA reductase inhibitors (statins), simvastatin and pravastatin, suggests that aggressive treatment of diabetic dyslipidaemia will reduce coronary events. Questions regarding the prevention of cardiovascular events in diabetic patients are now being addressed in prospectively designed trials. The first question is, can aggressive treatment of dyslipidaemia lead to primary prevention of cardiovascular events in patients with type 2 diabetes? This is being addressed in the ongoing Atorvastatin Study for the Prevention of coronary heart disease Endpoints in NIDDM (ASPEN) and the Collaborative AtoRvastatin Diabetes Study (CARDS). These trials will randomize over 4000 patients with type 2 diabetes and no previous myocardial infarction to either atorvastatin or placebo for 4 years. The second question is, are there benefits for aggressive lipid lowering to levels below those recommended in current treatment guidelines, i.e. is lower better? Results from the recent Atorvastatin VErsus Revascularization Treatment (AVERT) trial suggest this to be the case. AVERT showed that, in stable coronary heart disease patients who had been referred for revascularization, aggressive lowering of low density lipoprotein (LDL) cholesterol with atorvastatin 80 mg/day (to a mean level of 2.0 mmol/L [77 mg/dL]) reduced the incidence of ischaemic events by 36% compared with angioplasty and usual care (which reduced LDL cholesterol to 3.1 mmol/L [119 mg/dL]). The 36% reduction in events with atorvastatin versus angioplasty and usual care trended towards significance (p=0.048). The benefits of aggressive lipid-lowering therapy are also being investigated in the ongoing Treating to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid lowering (IDEAL) trials. These studies will more closely examine the benefits of treating diabetic dyslipidaemia, and will determine how aggressively this abnormal lipid profile should be treated.
Insights
Aggressive statin therapy for diabetic dyslipidemia shows promise in preventing cardiovascular events. Ongoing trials investigate optimal lipid-lowering targets for type 2 diabetes patients.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Diabetic dyslipidemia significantly increases cardiovascular event risk.
- Preliminary evidence suggests statins (simvastatin, pravastatin) reduce coronary events in diabetics.
- Prospective trials are crucial to confirm cardiovascular event prevention in type 2 diabetes.
Purpose of the Study:
- To assess if aggressive dyslipidemia treatment prevents cardiovascular events in type 2 diabetes (primary prevention).
- To determine if lowering low-density lipoprotein (LDL) cholesterol below current guidelines (i.e., "lower is better") offers additional benefits.
- To investigate the benefits of aggressive lipid-lowering therapy in diabetic patients.
Main Methods:
- The Atorvastatin Study for the Prevention of coronary heart disease Endpoints in NIDDM (ASPEN) and Collaborative AtoRvastatin Diabetes Study (CARDS) will randomize over 4000 type 2 diabetes patients (no prior myocardial infarction) to atorvastatin or placebo for 4 years.
- The Atorvastatin VErsus Revascularization Treatment (AVERT) trial compared atorvastatin 80 mg/day to angioplasty/usual care in stable coronary heart disease patients.
- The Treating to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid lowering (IDEAL) trials are ongoing to further examine aggressive lipid-lowering benefits.
Main Results:
- AVERT showed atorvastatin 80 mg/day significantly reduced LDL cholesterol to 2.0 mmol/L (77 mg/dL) compared to 3.1 mmol/L (119 mg/dL) with angioplasty/usual care.
- Aggressive LDL lowering with atorvastatin in AVERT resulted in a 36% reduction in ischemic events (p=0.048) in stable coronary heart disease patients.
- Ongoing trials (ASPEN, CARDS, TNT, IDEAL) are designed to provide more definitive data on aggressive lipid management in type 2 diabetes.
Conclusions:
- Aggressive lipid-lowering therapy, exemplified by atorvastatin, demonstrates potential for primary prevention of cardiovascular events in type 2 diabetes.
- The "lower is better" hypothesis is supported by AVERT findings, suggesting benefits of achieving very low LDL cholesterol levels.
- Further research through large-scale, prospective trials is essential to establish optimal treatment strategies for diabetic dyslipidemia and cardiovascular risk reduction.