Clinical Question

Does treatment aimed at increasing high-density lipoprotein (HDL) levels, in addition to treatment with statins, decrease cardiovascular events and deaths due to any cause?

Bottom Line

Being the “good” cholesterol is not the same as being the “useful” cholesterol. Drug therapy aimed at increasing HDL cholesterol levels, when added to statin treatment, does not decrease patients' likelihood of experiencing a cardiovascular event or of dying earlier. (Level of Evidence = 1a)

Synopsis

The researchers searched three databases, including the Cochrane Library, reference lists of previous meta-analyses and reviews, and conference proceedings to find large randomized trials (more than 1,000 patients) that compared drugs aimed at increasing HDL cholesterol levels vs. various interventions that do not increase HDL levels. Two authors independently completed the searches, and three authors extracted the data. They found 11 studies of niacin, 20 studies of fibrates, and eight studies of cholesteryl ester transfer protein (CETP) inhibitors such as anacetrapib and dalcetrapib (this class of drugs is not available in the United States, Canada, or the United Kingdom). All told, the studies enrolled more than 100,000 patients and found that attempting to increase the HDL level conferred no benefit on all-cause mortality, coronary heart disease mortality, or stroke likelihood. The problem, if you want to call it that, is the effect of statins—studies conducted in the current “statin era” do not show an added benefit of trying to bump HDL levels even though early studies of niacin by itself showed a pronounced effect in reducing nonfatal myocardial infarction.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Reference: KeeneDPriceCShun-ShinMJFrancisDPEffect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ2014; 349: g4379.