Researchers evaluated the biochemical effects, safety, and tolerability of evacetrapib as monotherapy and in combination with statins, in patients with dyslipidaemias.

The controlled trial involved 398 patients with elevated low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels randomised to receive placebo (n = 38); evacetrapib monotherapy, 30 mg/day (n = 40), 100 mg/day (n = 39), or 500 mg/day (n = 42); or statin therapy (n = 239) (simvastatin, 40 mg/day; atorvastatin, 20 mg/day; or rosuvastatin, 10 mg/day) with or without evacetrapib, 100 mg/day, for 12 weeks. The co–primary end points were percentage changes from baseline in HDL-C and LDL-C after 12 weeks of treatment.

The following results were reported:

• As monotherapy, evacetrapib produced dose-dependent increases in HDL-C of 0.78 to 1.70 mmol/L (53.6% to 128.8%) compared with a decrease with placebo of −0.02 mmol/L (−3.0%; P < 0.001 for all compared with placebo)

• As monotherapy, evacetrapib produced dose-dependant decreases in LDL-C of -0.53 to to −1.33 mmol/L (−13.6% to −35.9%) compared with an increase with placebo of 0.19 mmol/L (3.9%; P < 0.001 for all compared with placebo).

• In combination with statin therapy, evacetrapib, 100 mg/day, produced increases in HDL-C of 1.09 to 1.31 mmol/L (78.5% to 88.5%; P < 0.001 for all compared with statin monotherapy) and decreases in LDL-C of −1.74 to −1.96 mmol/L (−11.2% to −13.9%; P < 0.001 for all compared with statin monotherapy).

• Compared with evacetrapib monotherapy, the combination of statins and evacetrapib resulted in greater reductions in LDL-C (P <0.001) but no greater increase in HDL-C (P =0.39).

• A greater increase in diastolic blood pressure was observed when evacetrapib, 100 mg/day, was administered in combination with simvastatin, 40 mg/day, compared with simvastatin monotherapy (P=0.02).

• Overall, there was no difference between evacetrapib and control groups in either the monotherapy or statin combination studies with regard to the rate of treatment-related adverse events and discontinuation rates.

The researchers concluded that evacetrapib as monotherapy or combination therapy with statins produced favourable changes in HDL-C and LDL-C, although these need to be verified in terms of cardiovascular clinical outcomes.

Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor.

A related editorial discusses the study.