Conclusions : CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality .
There is a trend towards small reductions in nonfatal MI and cardiovascular death , though the clinical importance of such reductions is likely modest
Background : Cholesteryl ester transfer protein ( CETP ) inhibitors increase serum high-density lipoprotein cholesterol ( HDL-c ) concentration ; however , their impact on cardiovascular outcomes is not clear .
This systematic review examines the effect of CETP inhibitors on serum lipid profiles , cardiovascular events , and all-cause mortality .
Effects of torcetrapib in patients at high risk for coronary events.
BACKGROUND Inhibition of cholesteryl ester transfer protein ( CETP ) has been shown to have a substantial effect on plasma lipoprotein levels . We investigated whether torcetrapib , a potent CETP inhibitor , might reduce major cardiovascular events . The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib .  METHODS We conducted a r and omized , double-blind study involving 15,067 patients at high cardiovascular risk . The patients received either torcetrapib plus atorvastatin or atorvastatin alone . The primary outcome was the time to the first major cardiovascular event , which was defined as death from coronary heart disease , nonfatal myocardial infa rct ion , stroke , or hospitalization for unstable angina . RESULTS At 12 months in patients who received torcetrapib , there was an increase of 72.1 % in high-density lipoprotein cholesterol and a decrease of 24.9 % in low-density lipoprotein cholesterol , as compared with baseline ( P<0.001 for both comparisons ) , in addition to an increase of 5.4 mm Hg in systolic blood pressure , a decrease in serum potassium , and increases in serum sodium , bicarbonate , and aldosterone ( P<0.001 for all comparisons ) . There was also an increased risk of cardiovascular events ( hazard ratio , 1.25 ; 95 % confidence interval [ CI ] , 1.09 to 1.44 ; P=0.001 ) and death from any cause ( hazard ratio , 1.58 ; 95 % CI , 1.14 to 2.19 ; P=0.006 ) . Post hoc analyses showed an increased risk of death in patients treated with torcetrapib whose reduction in potassium or increase in bicarbonate was greater than the median change . CONCLUSIONS Torcetrapib therapy result ed in an increased risk of mortality and morbidity of unknown mechanism . Although there was evidence of an off-target effect of torcetrapib , we can not rule out adverse effects related to CETP inhibition . ( Clinical Trials.gov number , NCT00134264 [ Clinical Trials.gov ] . )
Conclusions : CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality .
There is a trend towards small reductions in nonfatal MI and cardiovascular death , though the clinical importance of such reductions is likely modest
Background : Cholesteryl ester transfer protein ( CETP ) inhibitors increase serum high-density lipoprotein cholesterol ( HDL-c ) concentration ; however , their impact on cardiovascular outcomes is not clear .
This systematic review examines the effect of CETP inhibitors on serum lipid profiles , cardiovascular events , and all-cause mortality .