HPS3/TIMI55-REVEAL: CETP Inhibition With Anacetrapib Reduced Major Cardiac Events in Atherosclerotic Vascular Disease

The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib significantly reduced the risk of major coronary events in patients with atherosclerotic vascular disease, according to study results presented by Martin Landray, MD, on Aug. 29 at ESC Congress 2017 in Barcelona. The results were simultaneously published in the New England Journal of Medicine by the HPS3/TIMI55-REVEAL Collaborative Group.

In patients treated with intensive atorvastatin therapy, the primary composite outcome – the first occurrence of coronary death, myocardial infarction (MI) or coronary revascularization – was significantly lower with anacetrapib (100 mg once daily) compared with placebo after a median follow-up of 4.1 years. A primary outcome event occurred in 1,640 of 15,225 (10.8 percent) patients treated with anacetrapib vs. 1,803 of 15,224 (11.8 percent) patients receiving placebo (rate ratio, 0.91; 95 percent confidence interval [CI], 0.85-0.97; p = 0.004).

At baseline, patients had a mean high-density lipoprotein cholesterol (HDL-C) level of 40 mg/dl, a mean low-density lipoprotein cholesterol (LDL-C) of 61 mg/dl and a mean non–HDL-C level of 92 mg/dl.  At the midpoint of the randomized, controlled, double-blind trial, an analysis showed that the mean HDL-C was 43 mg/dl higher with anacetrapib vs. placebo (relative difference of 104 percent) and the mean non–HDL-C was lower by 17 mg/dl (relative difference of –18 percent).

For the primary outcome, the relative difference in risk was similar across multiple prespecified subgroup analyses. The rate of major coronary events occurring more than one year after randomization was significantly lower in the anacetrapib group compared with the placebo group (rate ratio, 0.88; 95 percent CI, 0.81-0.95; p = 0.001), but there was no significant difference between the groups in the rate of major coronary events occurring during the first year of follow-up.

In a separate analysis of the individual components of the primary outcome, the risk of MI was lower with anacetrapib than placebo (rate ratio, 0.87; 95 percent CI, 0.78-0.96; p = 0.007). No significant difference was observed in the risk of coronary death between groups. The rate of MI or coronary death was significantly lower with anacetrapib vs. placebo (rate ratio, 0.89; 95 percent CI, 0.81-0.97; p = 0.008). Fewer patients in the anacetrapib group required urgent coronary revascularization vs. placebo (rate ratio, 0.90; 95 percent CI, 0.83-0.97; p = 0.01).

The secondary outcome of major vascular events occurred more frequently with anacetrapib. There were no significant between-group differences in the risk of death, cancer or other serious adverse events.

“We found that the addition of the CETP inhibitor anacetrapib to intensive statin treatment in patients with atherosclerotic vascular disease resulted in a significantly lower incidence of major coronary events than the addition of placebo during 4 years of treatment,” concluded the authors. These results contrast with those reported from trials of other CETP inhibitors, which found no benefit over placebo.


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