Does the cholesteryl ester transfer protein inhibitor anacetrapib improve outcomes in patients with known vascular disease and a low LDL level who are already taking a statin?

In patients with known cardiovascular (CV) disease who are taking a statin, adding the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib has no effect on mortality but slightly reduces the likelihood of a major vascular event (number needed to treat [NNT] = 111 over 4.1 years). If the drug costs US$300 per month (it is not yet available), it would cost approximately US$1.6 million to prevent that one event. (LOE = 1b)

The HPS3/TIMI55REVEAL Collaborative Group, Bowman L, Hopewell JC, et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. N Engl J Med 2017;377(13):1217-1227.  [PMID:28847206]

Randomized controlled trial (double-blinded)

Industry

Uncertain

Outpatient (any)

Previous studies of CETP inhibitors have not shown any clinical benefit, and some have shown net harm. Anacetrapib is a CETP inhibitor that has been shown to be relatively safe in previous studies, although no benefit was seen in smaller trials of patients at high risk for CV disease. The current study enrolled 30,449 persons 50 years and older with known vascular disease (88% coronary heart disease, 22% cerebrovascular disease, 8% peripheral vascular disease) and gave them atorvastatin to achieve an LDL cholesterol level of less than 77 mg/dL (2 mmol/L) and a total cholesterol level of less than 155 mg/dL (4 mmol/L). They were then randomized to receive anacetrapib 100 mg once daily or matching placebo. The groups were balanced at baseline, with a mean age of 68 years, a mean LDL of 61 mg/dL while taking a statin, and a mean high-density lipoprotein (HDL) of 40 mg/dL. Follow-up was excellent over a median of 4.1 years. As expected, patients in the intervention group had a lower mean LDL level (38 vs 65 mg/dL) and a higher HDL level (85 vs 42 mg/dL). There was no efffect on all-cause mortality, CV mortality, incidence of cancer, or non-CV mortality.There was a small decrease in the primary combined outcome of CV death, myocardial infarction, and revascularization (10.8% vs 11.8%; P = .004; NNT = 100), primarily due to a decrease in the risk of myocardial infarction (4.4% vs 5.1%; P = .007; NNT = 143 over 4.1 years). The risk of any major vascular event was also slightly lower (13.6% vs 14.5%; P = .02; NNT = 111 over 4.1 years). The drug was well tolerated.