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09-09-2010 | Cardiometabolic | Article

HDL link to noncardiovascular mortality refuted


Free abstract

MedWire News: Raising patients' levels of high-density lipoprotein (HDL) cholesterol should not increase their risk for noncardiovascular mortality, conclude the authors of a meta-analysis.

The Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial reported HDL cholesterol increases of more than 70% in patients treated with the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib, but also an increase in noncardiovascular mortality, relative to patients taking placebo. This led to the early termination of the trial.

The current meta-analysis, conducted by Elena Burillo (Hospital Universitario Miguel Servet, Saragossa, Spain) and colleagues and published in the journal Heart, aimed to distinguish the effects of the mechanism of raising HDL cholesterol from the HDL cholesterol rise per se.

The analysis included 44 randomized trials in which the active treatment group achieved more than a 4% increase in HDL cholesterol, compared with the placebo group. Active treatments included statins, fibrates, niacin, and hormone replacement, which were associated with HDL cholesterol increases of 4-10%, 4-14%, 10-38%, and 8-11%, respectively. None of these major classes of treatment were associated with increased noncardiovascular mortality versus placebo.

Other treatments included sibutramine (9-11% increase) and torcetrapib (72% increase).

Overall, the risk for noncardiovascular death rose significantly in line with the percent HDL cholesterol increase achieved in patients on active treatment.

However, this association completely disappeared when the researchers excluded ILLUMINATE, which contributed about 15,000 of the 107,773 patients in the meta-analysis.

Burillo et al stress: "Our study does not exclude the possibility that very large increases in HDL cholesterol over 50% might have an effect on noncardiovascular death."

But they suggest that "drug mechanisms," rather than the large HDL cholesterol rises, may underlie the excess noncardiovascular mortality seen in ILLUMINATE.

In an editorial accompanying the meta-analysis, Brian Tomlinson (Prince of Wales Hospital, Hong Kong, China) said: "Unfortunately, the meta-regression analysis from Burrilloa et al cannot answer the critical question of whether the increase in noncardiovascular mortality with torcetrapib in ILLUMINATE was due to off-target effects specific to torcetrapib or to raising HDL cholesterol by CETP inhibition.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Eleanor McDermid