Therapeutic manipulation of HDL fails to benefit adults with heart disease

N Engl J Med2012; doi:10.1056/NEJMoa1206797

Dalcetrapib increases serum concentrations of high density lipoprotein (HDL) cholesterol, and Hoffmann-La Roche developed this new drug in response to observational evidence that higher concentrations were associated with a lower risk of cardiovascular disease. Dalcetrapib failed to prevent cardiovascular events or deaths in a placebo controlled trial, however, despite increasing HDL cholesterol concentrations by 30-40%.

The authors tested their agent in 15 871 adults with a recent acute coronary syndrome. Participants took dalcetrapib or a placebo for two and a half years, alongside other recommended drugs. An independent data monitoring committee stopped the trial early when it became clear that dalcetrapib did not work. The authors had enough data by then to be 99% certain of the negative result. Dalcetrapib did not save lives or prevent heart attacks, strokes, non-fatal cardiac arrests, or admissions for unstable angina (cumulative rate of all outcomes combined 8.0% v 8.3%; hazard ratio with dalcetrapib 1.04, 95% CI 0.93 to 1.16). It did increase systolic blood pressure by 0.6 mm Hg (P<0.001), and it caused more hypertension, diarrhoea, and insomnia than the placebo. Dalcetrapib also increased serum concentrations of C reactive protein (1.6 v 1.4 mg/L (1 mg/L=9.52 nmol/L); P<0.001)

This trial may be the strongest indication yet that artificial manipulation of HDL cholesterol does not have the desired effect in people with coronary heart disease, say the authors.