Outcomes trials
Mendelian randomisation across ancestries: CETP inhibition should protect against cardiovascular disease equally in East Asian and European populations (Nat Commun 2024)
Original title: Comparing the effects of CETP in East Asian and European ancestries: a Mendelian randomization study
Genetic studies in East Asian populations had previously found a weaker link between CETP and LDL-C and no drug-target Mendelian randomisation effect on coronary heart disease, raising concern that CETP inhibitors might not work in East Asian patients. Using larger recent East Asian genetic datasets, this drug-target Mendelian randomisation study, scaled to a standard deviation increase in HDL-C, found that lower CETP levels had possible neutral effects on LDL-C, systolic blood pressure and pulse pressure specifically in East Asians compared with Europeans (interaction P values under 1.6E-3). Despite this, the effect of lower CETP on cardiovascular outcomes was similarly protective in both ancestry groups. The authors conclude on-target CETP inhibition is anticipated to reduce cardiovascular disease in both European and East Asian populations, directly relevant to the ongoing obicetrapib trials in Asian cohorts.
Original abstract
CETP inhibitors are a class of lipid-lowering drugs in development for treatment of coronary heart disease (CHD). Genetic studies in East Asian ancestry have interpreted the lack of CETP signal with low-density lipoprotein cholesterol (LDL-C) and lack of drug target Mendelian randomization (MR) effect on CHD as evidence that CETP inhibitors might not be effective in East Asian participants. Capitalizing on recent increases in sample size of East Asian genetic studies, we conducted a drug target MR analysis, scaled to a standard deviation increase in high-density lipoprotein cholesterol. Despite finding evidence for possible neutral effects of lower CETP levels on LDL-C, systolic blood pressure and pulse pressure in East Asians (interaction p-values < 1.6 × 10-3), effects on cardiovascular outcomes were similarly protective in both ancestry groups. In conclusion, on-target inhibition of CETP is anticipated to decrease cardiovascular disease in individuals of both European and East Asian ancestries.
ancestrygeneticsoutcomes trials
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.