By contrast, although dalcetrapib has little overall effect on LDL cholesterol, there was an apparent trend towards a slightly larger reduction in LDL cholesterol among those with the rs1967309 AA genotype in dal-OUTCOMES. 6 Figure 2 shows the observed effects of CETP inhibitor therapy on major vascular events by ADCY9 genotype in the original hypothesis-generating dal-OUTCOMES trial in which there was a 39% (95% CI, 8%–59%) proportional reduction with dalcetrapib in individuals with rs1967309 AA genotypes compared with a 27% (95% CI, 2%–58%) proportional increase in those with GG genotypes, yielding a significant interaction (interaction P add =0.001, interaction P geno =0.006).
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The sentences
In the ACCELERATE genetic study, which involves high proportions of genotyped individuals with cardiovascular events because of its case-control design, there was a nonsignificant trend that is directionally consistent with the dal-OUTCOMES result.
The interaction between anacetrapib and ADCY9 genotype on non-HDL cholesterol was marginally significant after adjustment for principal components of ancestry alone (interaction P add =0.03) but was attenuated after further adjustment for non-HDL cholesterol levels at randomization (interaction P add =0.30, interaction P geno =0.34).