Treatment effect of anacetrapib does not vary by ADCY9 genotype

NEW ORLEANS — There was no significant effect of ADCY9 on response to the cholesteryl ester transfer protein inhibitor anacetrapib for major vascular events, according to findings presented at the American College of Cardiology Scientific Session.

As Cardiology Today previously reported, in the REVEAL trial, anacetrapib (Merck) plus statin therapy reduced major coronary events compared with placebo plus statin therapy, but the treatment effect was small and Merck decided to stop commercial development.

Previous research indicated the treatment effect of cholesteryl ester transfer protein (CETP) inhibitors may vary by genotype, so the researchers analyzed the REVEAL population for signals of treatment effect based on ADCY9 genotype, Jemma C. Hopewell, PhD, FESC, associate professor and senior scientist in genetic epidemiology and clinical trials in the Nuffield Department of Public Health, University of Oxford, said during a presentation.

“We have seen ADCY9 genotype-dependent treatment effects of plaque regression, C-reactive protein and cholesterol efflux,” she said. “Experimental data suggest that, in the absence of CETP activity, ADCY9 inactivation protects against atherosclerosis.”

The researchers analyzed 19,210 participants from REVEAL for whom genotyping was available (mean age, 68 years; 86% men). The primary outcome was major vascular events, including coronary death, MI, coronary revascularization and presumed ischemic stroke.

Among the cohort, 13% had major vascular events during the study period.

There was no significant effect of ADCY9 on response to the cholesteryl ester transfer protein inhibitor anacetrapib for major vascular events, according to findings presented at the American College of Cardiology Scientific Session.

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There were no meaningful differences by genotype on the effect of anacetrapib on HDL or non-HDL, Hopewell said.

The treatment effect of anacetrapib did not differ by ADCY9 genotype for reduction of major vascular events (HR for GG = 0.92; 95% CI, 0.81-1.05; HR for AG = 0.94; 95% CI, 0.84-1.06; HR for AA = 0.93; 95% CI, 0.76-1.13), according to the researchers.

There were also no differences by genotype in treatment effect of anacetrapib for the individual components of the primary outcome, Hopewell said.

“REVEAL provides no evidence to support a material effect of ADCY9 on response to anacetrapib,” she said. “Further studies will assess whether any other genetic variants can identify individuals who obtain particular benefit from anacetrapib.” – by Erik Swain

Reference:

Hopewell JC, et al. Featured Clinical Research III. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.

Disclosures: The study was supported by Merck. Hopewell reports no relevant financial disclosures.