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Lipid-lowering treatment in coronary artery disease: how low should cholesterol go?
1Section of Atherosclerosis and Lipid Research, Baylor College of Medicine, Houston, Texas 77030, USA. jones@bcm.tmc.edu
Insights
Lowering low-density lipoprotein cholesterol (LDL-C) with statins significantly reduces coronary heart disease (CHD) events. New trials suggest even lower LDL-C targets may offer greater benefits without increased risks.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Substantial evidence supports lowering low-density lipoprotein cholesterol (LDL-C) to prevent coronary heart disease (CHD) events.
- HMG-CoA reductase inhibitors (statins) are effective and well-tolerated for LDL-C reduction.
- Previous guidelines (1993 NCEP) set an LDL-C goal of <= 100 mg/dl for CHD patients but lacked guidance on lower limits due to limited data.
Purpose of the Study:
- To re-examine the optimal LDL-C target for CHD prevention based on recent clinical trial data.
- To assess the efficacy and safety of achieving progressively lower LDL-C levels.
- To determine if further LDL-C reduction below 100 mg/dl offers additional clinical benefit.
Main Methods:
- Analysis of on-treatment LDL-C levels and CHD events from three landmark statin trials.
- Review of results from trials like Post-CABG and AVERT comparing intensive vs. less intensive statin regimens.
- Evaluation of ongoing trials randomizing CHD patients to LDL-C targets of 100 mg/dl versus 75 mg/dl.
Main Results:
- Progressively lower LDL-C levels are associated with a reduction in CHD events in a curvilinear manner.
- More intensive statin therapy in Post-CABG and AVERT trials led to better angiographic and clinical outcomes.
- No significant increase in noncardiovascular adverse events was observed with lower LDL-C levels.
Conclusions:
- Recent clinical trials provide sufficient data to support re-evaluating LDL-C targets for CHD patients.
- Achieving LDL-C levels around 75 mg/dl may offer an acceptable benefit-to-risk ratio.
- Ongoing trials are crucial to definitively establish the safety and efficacy of very low LDL-C targets.
Abstract:
The randomised clinical trial data, which supports preventing coronary heart disease (CHD) events by lowering low density lipoprotein cholesterol (LDL-C) levels, is substantial, consistent and highly significant. HMG-CoA reductase inhibitors (statins), which are the preferred medications for lowering LDL-C levels, are well tolerated, with greater efficacy than other lipid-altering medications. In 1993, the National Cholesterol Education Program (NCEP) guidelines recommended LDL-C target levels to be achieved with therapy in high-risk individuals. In particular, the LDL-C goal of therapy in patients with CHD was < or = 100 mg/dl (2.6 mmol/L), with no specific guidance as to the lower limit or whether additional clinical benefit could be expected. Because little clinical trial data existed at that time to offer support, and because some epidemiological data raised concern about the potential detriments associated with very low total cholesterol and LDL-C levels, the NCEP Adult Treatment Panel remained appropriately vague on the 'how low should you go' question. In the last few years, several additional clinical trials have provided sufficient efficacy and safety data to re-examine that question. Analyses of on-treatment LDL-C levels and subsequent CHD events from three landmark trials with HMG-CoA reductase inhibitors suggest that progressively lower LDL-C levels are associated with lower CHD events in a curvilinear fashion. The Post Coronary Artery Bypass Graft (Post-CABG) trial and Atorvastatin Versus Revascularisation Trial (AVERT) examined a more intensive versus less intensive drug regimen for LDL-C reduction, and concluded that the more aggressively treated patients had better angiographic and end-point outcomes. Most importantly, there did not appear to be any change in noncardiovascular end-points associated with lower LDL-C levels. In several ongoing clinical trials, patients with CHD have been randomised to receive HMG-CoA reductase inhibitors with targets for LDL-C levels of 100 mg/dl versus 75 mg/dl (1.94 mmol/L). These trials have sufficient patient numbers and power to definitely determine if reducing LDL-C levels to approximately 75 mg/dl can provide an acceptable benefit-to-risk-ratio.