[Torcetrapib increases mortality in patients with a high risk of cardiovascular disorders].
Inhibition of cholesteryl ester transfer protein (CETP) is generally regarded as a promising strategy to reduce atherosclerosis by increasing HDL cholesterol. Therefore, the potent CETP inhibitor torcetrapib was given in addition to atorvastatin in half of the 15,067 patients with a high cardiovascular risk in the randomized, double-blind 'Investigation of lipid level management to understand its impact in atherosclerotic events' (ILLUMINATE) study. Torcetrapib caused a large increase of 72.1% in HDL cholesterol and a concomitant reduction of 24.9% in LDL-cholesterol. However, the trial was terminated prematurely because of an increased risk of cardiovascular events and death. Besides increasing blood pressure, torcetrapib decreased potassium and increased sodium, bicarbonate and aldosterone in serum. Post hoc analyses showed an increased risk of death in patients whose change in electrolytes was greater than the median change. These adverse effects of torcetrapib are presumably compound-specific, but should be taken into account in future studies with novel CETP inhibitors. Furthermore, it is suggested that the efficacy of CETP inhibition with regard to cardiovascular event reduction may depend on the lipid profile of the patient.
Afd. Interne Geneeskunde en Endocrinologie, Leids Universitair Medisch Centrum, Postbus 9600, 2300 RC Leiden.
P C N
PC
Rensen
J W
JW
Jukema
D000924:Anticholesteremic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D018579:Patient Selection; D011804:Quinolines / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014882:Water-Electrolyte Balance / Q000187:drug effects* / Q000502:physiology
D000924:Anticholesteremic Agents; D011804:Quinolines; C483909:torcetrapib