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Effect of C-Reactive Protein on Lipoprotein(a)-Associated Cardiovascular Risk in Optimally Treated Patients With High-Risk Vascular Disease: A Prespecified Secondary Analysis of the ACCELERATE Trial

R. Puri, Steven E. Nissen, B. Arsenault, J. St. John, J. Riesmeyer, G. Ruotolo, E. McErlean, V. Menon et al.

JAMA cardiology, 2020

8,135 participants · 109 citations

Abstract

Importance

Although lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease, it remains unclear which patients with established atherosclerotic cardiovascular disease stand to benefit the most from Lp(a) lowering. Whether inflammation can modulate Lp(a)-associated cardiovascular (CV) risk during secondary prevention is unknown.

Objective

To examine whether Lp(a)-associated CV risk is modulated by systemic inflammation in optimally treated patients at high risk of CV disease.

Design, Setting, and Participants

A prespecified secondary post hoc analysis of the double-blind, multicenter randomized clinical Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes (ACCELERATE) trial was conducted between October 1, 2012, and December 31, 2013; the study was terminated October 12, 2015. The study was conducted at 543 academic and community hospitals in 36 countries among 12 092 patients at high risk of CV disease (acute coronary syndrome, stroke, peripheral arterial disease, or type 2 diabetes with coronary artery disease) with measurable Lp(a) and high-sensitivity C-reactive protein (hsCRP) levels during treatment. Statistical analysis for this post hoc analysis was performed from September 26, 2018, to March 28, 2020.

Interventions

Participants received evacetrapib, 130 mg/d, or matching placebo.

Main Outcomes and Measures

The ACCELERATE trial found…

How strong is the evidence?

Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 8,135 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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