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Comment & Response
January 2, 2020

Interpreting the Benefit of Simvastatin-Ezetimibe in Patients 75 Years or Older—Reply

Author Affiliations
  • 1Cardiovascular Division, Washington University Medical Center, St Louis, Missouri
  • 2Brigham and Women’s Hospital, Boston, Massachusetts
  • 3Duke Clinical Research Institute; Duke University, Durham, North Carolina
JAMA Cardiol. 2020;5(2):235-236. doi:10.1001/jamacardio.2019.5241

In Reply On behalf of our coauthors, we thank Weingärtner et al and Li et al for their interest in our article.1 Weingärtner et al suggest that the strong benefit of adding ezetimibe to simvastatin observed in patients 75 years and older may be explained by a higher proportion of cholesterol absorption compared with endogenous synthesis among older compared with younger patients. While we find their proposed mechanism intriguing, we feel it important to point out that (1) not only older individuals but also other higher risk subgroups within the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) showed greater benefit of ezetimibe added to simvastatin2,3 and (2) the observed levels of low-density lipoprotein cholesterol reduction by ezetimibe added to simvastatin did not appear greater among patients 75 years or older vs younger patients (eTable 3 in Supplement 21). Nevertheless, we share their interest in the relationship of markers of cholesterol absorption and outcomes, and such an analysis is ongoing in IMPROVE-IT. While we also agree that efforts to personalize therapy hold promise to maximize the benefit of differing treatments, including lipid lowering, prospective randomized clinical trial data will be needed to confirm that determining the ratio of cholesterol absorption to synthesis before starting lipid-lowering treatment will result in superior outcomes. Meanwhile, the benefit of ezetimibe added to simvastatin observed among elderly patients in IMPROVE-IT suggests a simple intervention available now to improve outcomes for a broad population of elderly patients in current practice.

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