Epidemiologic Modeling of US Cholesterol Treatment And Cardiovascular Outcomes Based On US And European Guidelines

Monday, August 26, 2024

5:45 PM – 6:00 PM CEST

Location: Auditorium

Presenting Author(s)

G. Caleb Alexander, MD

Professor of Epidemiology and Medicine
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
Baltimore, United States

Co-Author(s)

JC

Jill Curran

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
AV

Alejandro Victores

Merck & Co., Inc., Rahway, New Jersey, US, United States
Hemalkumar B. Mehta, MS, PhD (he/him/his)

Associate Professor
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health
Baltimore, United States
Shanshan Lin, ScM

Research data analyst
Johns Hopkins University, School of Medicine, Division of General Internal of Medicine, United States
Xuya Xiao, MHS (she/her/hers)

Research analyst
Johns Hopkins Bloomberg School of Public Health, United States
EM

Erin D. Michos

Division of Cardiology, Johns Hopkins Medicine, Baltimore, Maryland, United States
JB

Jeromie Ballreich

Assistant Scientist
Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
LB

Lori D. Bash

Merck & Co., Inc., Rahway, New Jersey, US, United States
JE

Jason Exter

Merck & Co., Inc., Rahway, New Jersey, US, United States
SM

Seth S. Martin

Division of Cardiology, Johns Hopkins Medicine, Baltimore, Maryland, United States
KF

Kathryn Foti

Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, United States

Background: The population-level benefits of pharmacologic treatment fully concordant with major guideline recommendations on lipid management have not been well quantified.

Objectives: To project anticipated improvements in lipid lowering therapy use, low-density lipoprotein cholesterol (LDL-C) control, and subsequent cardiovascular outcomes that could be expected under full implementation of US and European pharmacologic treatment recommendations.

Methods: In this cross-sectional study, we included participants aged 40-75 years in the fasting subsample from the 2013 through March 2020 US National Health and Nutrition Examination Survey (NHANES). We estimated the number of individuals eligible to receive versus currently receiving lipid lowering therapy (LLT) for the primary prevention cohort and secondary prevention cohort. We separately simulated treatment progression and reductions in cardiovascular events based on LDL-C threshold after applying: (1) the American College of Cardiology/ American Heart Association guideline (“2018 US guideline”); (2) the European Society of Cardiology/European Atherosclerosis Society guideline (“2019 EU guideline”); and (3) the American College of Cardiology expert decision pathway (“2022 US pathway”). Our primary outcome includes (1) Number of individuals eligible for LLT; and (2) expected reduction in LDL-C and (3) major cardiovascular events, including coronary death, non-fatal myocardial infarction, coronary revascularization, and stroke.

Results: The study sample included 4980 adults aged 40-75 years, representing 131 million US adults. A total of 23% of the NHANES primary prevention cohort was currently using LLT compared to those eligible in the 2018 US guideline/2022 US pathway (47% eligible) and the 2019 EU guideline (87% eligible). Approximately 68% of the NHANES secondary prevention cohort was using LLT despite 100% eligibility. And LLT use was significantly lower than the proportion of eligible patients for all therapies, including statins (66% use vs. 100% eligibility), ezetimibe (4% vs 33-76% across 3 recommendations), and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) (0% vs 12-53% eligibility across 3 recommendations). In the overall cohort, the additional overall median LDL-C reduction expected under full guideline-concordant care was 37.2 (IQR 6.7-57.6) mg/dL, 48.5 (IQR 33.0-69.9) mg/dL, and 46.8 (IQR 7.2-67.6) mg/dL based on the 2018 US guideline, 2019 EU guideline and the 2022 US pathway, respectively. These reductions in LDL-C could yield a 21-27% relative reduction in risk of major cardiovascular events.

Conclusions: Aligning treatment of hypercholesterolemia with US and European guidelines would generate major clinical and public health gains.