TY - JOUR
T1 - Relationship between atorvastatin dose and the harm caused by torcetrapib
AU - Barter, Philip J.
AU - Rye, Kerry-Anne
AU - Beltangady, Mohan S.
AU - Ports, William C.
AU - Duggan, William T.
AU - Boekholdt, S. Matthijs
AU - Demicco, David A.
AU - Kastelein, John J. P.
AU - Shear, Charles L.
PY - 2012
Y1 - 2012
N2 - Development of the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, was halted after the ILLUMINATE trial revealed an increase in both all-cause mortality (ACM) and major cardiovascular events (MCVEs) associated with its use. We now report that the harm caused by torcetrapib was confined to those in the 10 mg atorvastatin subgroup for both ACM [hazard ratio (HR) = 2.68, 95% CI (1.58, 4.54), P <0.0001] and MCVEs [HR = 1.41, 95% CI (1.14, 1.74), P = 0.002], with no evidence of harm when torcetrapib was coadministered with higher doses of atorvastatin. In the atorvastatin 10 mg subgroup, age, prior heart failure and stroke were significantly associated with ACM, independent of torcetrapib treatment, whereas low apoA-I, smoking, hypertension, heart failure, myocardial infarction, and stroke were independently associated with MCVEs. After adjusting for these factors, the HR associated with torcetrapib treatment in the 10 mg atorvastatin subgroup remained elevated for both ACM [HR = 2.67, 95% CI (1.57, 4.54), P <0.001] and MCVE [HR = 1.36, 95% CI (1.10, 1.69), P = 0.005]. Thus, the harm caused by torcetrapib was confined to individuals taking atorvastatin 10 mg. The harm could not be explained by torcetrapib-induced changes in lipid levels, blood pressure, or electrolytes. It is conceivable that higher doses of atorvastatin protected against the harm caused by torcetrapib.-Barter, P. J., K-A. Rye, M. S. Beltangady, W. C. Ports, W. T. Duggan, S. M. Boekholdt, D. A. DeMicco, J. J. P. Kastelein, and C. L. Shear. Relationship between atorvastatin dose and the harm caused by torcetrapib. J. Lipid Res. 2012. 53: 2436-2442
AB - Development of the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, was halted after the ILLUMINATE trial revealed an increase in both all-cause mortality (ACM) and major cardiovascular events (MCVEs) associated with its use. We now report that the harm caused by torcetrapib was confined to those in the 10 mg atorvastatin subgroup for both ACM [hazard ratio (HR) = 2.68, 95% CI (1.58, 4.54), P <0.0001] and MCVEs [HR = 1.41, 95% CI (1.14, 1.74), P = 0.002], with no evidence of harm when torcetrapib was coadministered with higher doses of atorvastatin. In the atorvastatin 10 mg subgroup, age, prior heart failure and stroke were significantly associated with ACM, independent of torcetrapib treatment, whereas low apoA-I, smoking, hypertension, heart failure, myocardial infarction, and stroke were independently associated with MCVEs. After adjusting for these factors, the HR associated with torcetrapib treatment in the 10 mg atorvastatin subgroup remained elevated for both ACM [HR = 2.67, 95% CI (1.57, 4.54), P <0.001] and MCVE [HR = 1.36, 95% CI (1.10, 1.69), P = 0.005]. Thus, the harm caused by torcetrapib was confined to individuals taking atorvastatin 10 mg. The harm could not be explained by torcetrapib-induced changes in lipid levels, blood pressure, or electrolytes. It is conceivable that higher doses of atorvastatin protected against the harm caused by torcetrapib.-Barter, P. J., K-A. Rye, M. S. Beltangady, W. C. Ports, W. T. Duggan, S. M. Boekholdt, D. A. DeMicco, J. J. P. Kastelein, and C. L. Shear. Relationship between atorvastatin dose and the harm caused by torcetrapib. J. Lipid Res. 2012. 53: 2436-2442
U2 - https://doi.org/10.1194/jlr.P026328
DO - https://doi.org/10.1194/jlr.P026328
M3 - Article
C2 - 22941786
SN - 0022-2275
VL - 53
SP - 2436
EP - 2442
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 11
ER -