Inflammation Could Be Better Predictor of Cardiovascular Events than LDL-C, Study Finds

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Paul Ridker, MD, MPH, discusses the evolving recognition of the role inflammation plays in driving cardiovascular risk among patients with atherosclerosis.

Data from an analysis of more than 13,000 statin-intolerant patients is highlighting the impact of inflammation as a driver of cardiovascular risk.

Presented at the American Heart Association (AHA) Scientific Sessions 2023, results of the CLEAR Outcomes analysis demonstrate baseline hsCRP level was a more powerful predictor of future cardiovascular risk among patients included in the trial. Additional analysis suggested bempedoic acid consistent efficacy for major adverse cardiovascular events across all levels of hsCRP and LDL-C.1

Debuted at the American College of Cardiology 2023 Annual Scientific Session, CLEAR Outcomes provided clinicians with evidence of a 13% relative risk reduction for 4-point major adverse cardiovascular events among statin-intolerant patients with use of bempedoic acid. The results of the study, which purported a 27% risk reduction of non-fatal myocardial infarction and a 23% risk reduction of the composite of fatal and non-fatal myocardial infarction, were used as the basis of a Supplemental New Drug Application for cardiovascular risk reduction by Esperion in June 2023.2,3

At ACC.23, Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital presented data from a meta-analysis of the PROMINENT, STRENGTH, and REDUCE-IT trials, which concluded elevated hsCRP was associated with a 30% increase in relative risk of cardiovascular events and a more than doubling in risk of cardiovascular and all-cause mortality in fully adjusted analyses accounting for LDL-C and residual cholesterol risk.4

In the current study, Ridker and a team of investigators sought to assess the value of baseline hsCRP and LDL-C for predictors of future cardiovascular risk among a population not receiving statin therapy. To do so, investigators designed their study to compare quartiles of increasing baseline hsCRP and LDL-C for risk of a composite endpoint of myocardial infarction, stroke, coronary revascularization, and cardiovascular death after adjustment for traditional risk factors and treatment.1

When comparing the highest and lowest quartiles, results suggested baseline hsCRP was significantly associated with an increased risk of the incident composite endpoint (Hazard Ratio [HR], 1.43; 95% Confidence Interval [CI], 1.24-1.65), cardiovascular mortality (HR, 2.00; 95% CI, 1.53-2.61), and all-cause mortality (HR, 2.21; 95% CI, 1.79-2.73). Further analysis suggested this association was greater than that seen with baseline LDL-C quartiles future cardiovascular events was lower for the composite endpoint (HR, 1.19; 95% CI, 1.04-1.37) and neutral for cardiovascular mortality (HR, 0.90; 95% CI, 0.70-1.17) and all-cause mortality (HR, 0.95; 95% CI, 0.78-1.16).1

Investigators pointed out use of bempedoic acid was associated with a 21.6% reduction in median hsCRP levels and a 21.1% reduction in mean LDL-C levels at 6 months, with consistent efficacy for major adverse cardiovascular events across all levels of hsCRP and LDL-C.1

For more on the results of this study, how it complements data from a late breaker he presented at ACC.23, and how it informs management of atherosclerotic cardiovascular disease, check out our interview with Ridker from AHA 2023.

There were no listed disclosures for Ridker attached to this AHA 2023 abstract.


  1. Ridker PM, Lei L, Louie MJ, Haddad TM, Nicholls SJ, Lincoff AM, Libby P, Nissen SE. Inflammation and Cholesterol as Predictors of Cardiovascular Events and Risk Reduction With Bempedoic Acid Among Statin Intolerant Patients: An Analysis of the CLEAR Outcomes Trial. Paper presented at: American Heart Association Scientific Sessions 2023; November 10 - 13; Philadelphia, PA. Accessed November 10, 2023.
  2. Campbell P. Bempedoic acid reduces risk of mace by 13%, but proves no benefit on cardiovascular death. HCP Live. March 4, 2023. Accessed November 10, 2023.
  3. Esperion announces submission of Supplemental New Drug Applications to U.S. FDA for NEXLETOL® (bempedoic acid) tablet and NEXLIZET® (bempedoic acid and ezetimibe) tablet. Esperion Therapeutics, Inc. June 1, 2023. Accessed November 10, 2023.
  4. Campbell P. New study indicates inflammation could be major driver of Atherosclerotic Risk. HCP Live. March 10, 2023. Accessed November 10, 2023.