HDL-Raising Properties of Statins Are Clinically Relevant

February 06, 2007

February 6, 2007 (Cleveland, OH) – The benefits of statins are derived from both reductions in LDL cholesterol and increases in HDL cholesterol, a new post hoc analysis of four clinical trials shows [1]. In fact, the researchers found substantial regression of atherosclerosis when LDL-C was markedly reduced and HDL-C was increased by more than 7.5%.

Dr Stephen J Nicholls (Cleveland Clinic, OH) and colleagues report their findings in the February 7, 2007 issue of the Journal of the American Medical Association. "We know statins increase HDL moderately, and we found that this can have a substantial impact," Nicholls told heartwire .

"We showed this small change in HDL to be additive with the LDL lowering, which can be associated with regression of atherosclerosis," he added. "This is a substantial thing. The bottom line is that increasing HDL results in regression of plaque, reversing an 'irreversible' process."

However, he stressed that it remains to be determined whether the regression associated with these changes in lipids will translate into any meaningful reductions in clinical events and improved outcomes.

Increases in HDL independent predictor of benefit with statins

Statins increase HDL-C by around 5% to 15%, Nicholls noted, in comparison with the 50% to 60% increases in HDL-C seen with the much-hyped torcetrapib, which recently fell from grace, as reported by heartwire .

In the new analysis, Nicholls et al combined raw data from a total of 1455 patients with angiographic coronary disease in four prospective randomized trials--REVERSAL, ACTIVATE, ASTEROID, and CAMELOT. All the participants received statin treatment for 18 or 24 months and had serial intravascular ultrasound (IVUS) examinations analyzed by the same core laboratory.

Substantial atheroma regression (>5%) was observed in patients with levels of LDL-C less than the mean (87.5 mg/dL) and increases of HDL-C greater than the mean (7.5%; p<0.001) during treatment. No significant differences were found, however, with regard to clinical events.

"This, to our knowledge, is the first time that increases in HDL-C levels have been shown to be an independent predictor of a beneficial outcome with statin therapy," Nicholls et al observe. The results are also the first to correlate increases in HDL-C in statin-treated patients with favorable effects on disease progression, they note.

Relationship between the combination of level of LDL-C during treatment and change in HDL-C with atheroma progression or regression

Participants (n)

LDL-C level during treatment, mg/dL*

% change in HDL level

Changes in TAV mean, mm3





















TAV=total atheroma volume
†Comparison between all groups using analysis of covariance after controlling for any differences in baseline atheroma volume between groups

HDL-raising effects of statins"clinically relevant"

"These findings suggest that the increase in HDL-C that occurs during statin therapy is clinically relevant when combined with intensive lowering of LDL-C and should be considered in the selection of therapy and subsequent management of patients with CAD," the researchers state.

The results also provide further impetus for the concept that HDL-C is atheroprotective, says Nicholls.

He is not surprised, however, by the failure of the study to show any differences in clinical events, given the small numbers of patients and short follow-up period.

A large-scale clinical trial is needed to show that the beneficial effect of simultaneous lipid modulation on plaque progression results in fewer clinical events, he concludes.

  1. Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol and regression of atherosclerosis. JAMA 2007; 297:499-508.

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