Which patients benefit from lowering LDL to <100 mg/dL?

High-dose statins decrease MI more than standard doses
A 2008 meta-analysis of 29,395 high-risk patients in 7 trials examined high-dose compared with standard statin use for secondary prevention. Six trials used atorvastatin 80 mg daily as the high-dose regimen; 1 trial used simvastatin 80 mg daily. The standard regimens were 5 to 40 mg of pravastatin, simvastatin, atorvastatin, or lovastatin.

The weighted mean difference of LDL lowering between the 2 groups was 28 mg/dL (95% CI, 23-32 mg/dL), and fewer than 50% of patients achieved the treatment target (LDL <80 mg/dL). Nevertheless, intensive statin use decreased MIs compared with standard dosing (RR=0.83; 95% CI, 0.77-0.91).⁷

This meta-analysis included a key RCT, which enrolled 4162 high-risk patients and compared pravastatin 40 mg (standard therapy) with atorvastatin 80 mg (intensive therapy) over an average of 24 months. The pravastatin group achieved a median LDL of 95 mg/dL and the atorvastatin group achieved a median LDL of 62 mg/dL. The atorvastatin group had fewer deaths from any cause or a major cardiovascular event (RR=0.85; 95% CI, 0.76-0.95; NNT=25).⁸

Does benefit result from lower LDL, or some other statin effect?
Since most lipid studies have been done using a statin as the sole treatment agent, it is unclear whether patients benefit more from a lower LDL or from some effect of the statin medication class.⁹ Statins reduce the risk of cardiovascular events in patients with an elevated C-reactive protein,¹⁰ perhaps indicating an anti-inflammatory effect. However, fibrates and niacin have also been shown to decrease coronary events in high-risk patients in a few studies.^11,12

Recommendations

The NCEP Adult Treatment Panel III guidelines recommend treating high-risk patients to a target LDL of <100 mg/dL.¹ A target LDL of <70 mg/dL is optional for very-high-risk patients (TABLE).^1,3

The K/DOQI recommends that patients with stage 5 kidney disease be treated according to the NCEP guidelines for high-risk patients.² The expected release date for the NCEP Adult Treatment Panel IV guidelines is fall 2011.¹³

Acknowledgement
The authors gratefully acknowledge the work of Dr. Marguerite Elliott, who co-authored this Clinical Inquiry, and who passed away on February 15, 2010.