Abstract
The REVEAL trial with anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, has been one of the largest "lipid" studies conducted so far. Its aim was to confirm the hypothesis that an increase in high-density lipoprotein (HDL) cholesterol will reduce the cardiovascular risk.
The CETP transporter glycoprotein transfers cholesterol esters and triglycerides from HDL to the liver and to atherogenic lipoproteins. The result is an increase in HDL cholesterol and a variable decrease in low-density lipoprotein (LDL) cholesterol.
On the one hand, this effect is positive-i.e. a decreased concentration of cholesterol esters in atherogenic lipoproteins; on the other hand, there is a breaking of the cycle of cholesterol esters in the chain of macrophage-HDL-liver and VLDL/LDL. Previous studies with a number of other CETP inhibitors have failed to show a positive impact on the rates of atherothrombotic events or even demonstrated increased rates; therefore, the positive results of the secondary prevention REVEAL trial were surprising.
The decrease in LDL cholesterol was high-in comparison with placebo, there was a documented decrease of more than 40% while the increase in HDL cholesterol was more than two-fold. The primary outcome measure, the rate of major coronary events, decreased statistically significantly-almost by a tenth.
However, in absolute values, the decrease was small-only 1% for 4 years of treatment. The corresponding NNT (number needed to treat), i.e. the number of patients treated needed to prevent one bad outcome, was 400 patients a year.
However, it needs to be emphasized that these were patients who had achieved optimal LDL cholesterol levels prior to treatment. Although the result of the trial was only of borderline significance from the clinical viewpoint, in terms of treatment strategy for dyslipidaemia the study has yielded a wealth of knowledge.
First of all, it has shown that a decrease in LDL cholesterol iscrucial. Given the fact that the study included patients with a mean baseline of 1.6 mmol/L under statin treatment, it has been shown that even a further decrease in LDL cholesterol is beneficial.
Furthermore, it has been confirmed that increasing HDL cholesterol will not affect patient prognosis. In summary, the answer to the fundamental question "Is an increase in HDL cholesterol beneficial?" is negative.
Nevertheless, the evidence that an LDL cholesterol decrease even below the strict target level of 1.6 mmol/L favourably affects atherothrombotic events is certainly beneficial.