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Comment & Response
September 2018

Randomized Trial Needed to Confirm Whether Dalcetrapib Improves Outcomes for Specific ADCY9 Genotype—Reply

Author Affiliations
  • 1Cleveland Clinic Coordinating Center for Clinical Research, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
  • 2Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana
JAMA Cardiol. 2018;3(9):897-898. doi:10.1001/jamacardio.2018.2382

In Reply The letter from Pfeffer et al outlines the authors’ rationale for their belief that the AA genotype for the rs1967309 single-nucleotide polymorphism (SNP) in the ADCY9 gene is likely associated with a cardiovascular benefit in patients treated with the cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib. We believe that our analysis1 of the evacetrapib outcome trial provides a more precise and reliable estimate of any association between this SNP and cardiovascular outcomes in patients treated with CETP inhibitors. Our analysis had more cardiovascular events in patients treated with a CETP inhibitor with the AA genotype (n = 125) compared with the dalcetrapib analysis (n = 38).2 Estimates of relative risk based on only 38 events are statistically unstable and inherently low in reliability.

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