Which patients benefit from lowering LDL to <100 mg/dL?
PATIENTS WHO HAVE CORONARY HEART DISEASE (CHD) or are at high risk for CHD should aim for a low-density lipoprotein (LDL) target of <100 mg/dL. An LDL target of <70 mg/dL is an option for very-high-risk patients (strength of recommendation [SOR]: C, expert opinion).
The evidence also indicates that high-risk patients benefit from a statin—preferably in high doses—regardless of their baseline LDL or degree of LDL reduction with treatment (SOR: A, a large randomized controlled trial [RCT] and meta-analyses).
Evidence summary
The National Cholesterol Expert Panel (NCEP) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults defines high-risk patients as having known CHD, diabetes, noncoronary atherosclerotic disease, or multiple risk factors for CHD.1 (Moderate-or low-risk patients are defined as having a 10-year risk of CHD <20%.) The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) also includes in the high-risk group patients with stage 5 kidney disease (glomerular filtration rate <15 mL/min or on dialysis).2
The NCEP goes on to define very-high-risk patients as those with known CHD and multiple risk factors. These risks include acute coronary syndrome, diabetes, metabolic syndrome, or poorly controlled or severe risk factors, especially cigarette smoking.1
An LDL target of <100 mg/dL for high-risk patients and an optional target of <70 mg/dL for very-high-risk patients were determined by expert interpretation of evidence from large trials and meta-analyses of a log-linear relationship between LDL levels and CHD risk (TABLE).3,4
TABLE
Target LDL measurements for high-risk and very-high-risk patients1,2,7,8
| Risk level | Risk factors | Goal LDL |
|---|---|---|
| High | Known CHD OR Noncoronary atherosclerotic disease: abdominal aortic aneurysm, peripheral arterial disease, symptomatic carotid stenosis OR Stage 5 kidney disease (GFR <15 mL/min or on dialysis) OR Diabetes OR ≥2 of the following risk factors with 10-y risk of CHD >20%:
| <100 mg/dL |
| Very high | Known CHD AND Multiple major risk factors:
| (Optional) <70 mg/dL |
| BP, blood pressure; CHD, coronary heart disease; GFR, glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein. | ||
Lowering LDL reduces first coronary events in high-risk patients
A large 2005 meta-analysis pooled 90,056 high-risk patients in 14 trials of statin use compared with placebo (11 studies), no treatment (1 study), very-low-dose statin use (1 study), or usual care (1 study). Primary outcomes were a change in LDL cholesterol, all-cause mortality, CHD mortality, and non-CHD mortality.5
The meta-analysis showed that high-risk patients had a 21% reduction in the 5-year incidence of first major coronary events for every 39 mg/dL decrease in LDL cholesterol (relative risk [RR]=0.79; 95% confidence interval [CI], 0.77-0.81; number needed to treat [NNT]=27). A subanalysis of 447 high-risk patients with LDL levels <100 mg/dL at baseline found that the risk of major coronary events decreased with statin therapy, but the 99% CI included 1 (RR=0.75; 99% CI, 0.56-1.01).5
Simvastatin decreases MI and stroke regardless of baseline LDL
One RCT included in the meta-analysis warrants special attention. This study evaluated the use of simvastatin 40 mg daily compared with placebo for 5 years in 20,536 high-risk patients who were grouped according to initial LDL level (<115 mg/dL, 115-135 mg/dL, and >135 mg/dL). Simvastatin lowered the average patient’s LDL by 39 mg/dL (no CIs provided).6
Regardless of the baseline LDL, simvastatin decreased the rate of first myocardial infarction (MI), stroke, or need for revascularization compared with placebo (RR=0.76; 95% CI, 0.72-0.81; NNT=18). Subgroup analysis of 3421 high-risk patients with LDL levels <100 mg/dL at baseline showed fewer major coronary events with simvastatin than with placebo (RR=0.78; 95% CI, 0.68-0.90).6
