Evacetrapib
In ACCELERATE, a rising hsCRP trajectory over follow-up predicts MACE better than a single baseline reading, even when levels stay under 2 mg/L (Am J Cardiol 2022)
Original title: Longitudinal High-Sensitivity C-Reactive Protein and Longer-Term Cardiovascular Outcomes in Optimally-Treated Patients With High-Risk Vascular Disease
A post hoc analysis of the ACCELERATE trial of evacetrapib in 8,563 optimally-treated, high-risk vascular disease patients (mean age 64.6, 22% women) tested whether repeated high-sensitivity C-reactive protein (hsCRP) measurements over follow-up, rather than a single baseline value, predicted major adverse cardiovascular events (MACE) at 30 months. Patients who went on to have MACE (n = 961) had higher baseline hsCRP (1.77 vs 1.46 mg/L) and an upward trajectory during follow-up, even though median levels stayed under 2 mg/L at every time point in both groups. In multivariable models, higher longitudinal hsCRP was independently associated with MACE (hazard ratio 1.19 per SD, 95% CI, 1.10 to 1.29) and improved MACE prediction beyond baseline hsCRP alone. The authors propose longitudinal hsCRP as a novel marker of residual cardiovascular risk even when conventional hsCRP thresholds appear reassuring; a biomarker analysis within the evacetrapib trial population, not a report of the efficacy of the drug itself.
Original abstract
The relation between serial high-sensitivity C-reactive protein (hsCRP) and long-term major cardiovascular events (MACEs; cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) has not been explored in optimally-treated patients with atherosclerotic cardiovascular disease. We tested the hypothesis that longitudinal follow-up hsCRP (repeated measures over time) would associate with 30-month MACE rates. We performed a post hoc analysis of ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibitor with Evacetrapib in Patients with High-Risk for Vascular Outcomes), involving optimally-treated patients with high-risk vascular disease, with available baseline and at least 1 follow-up hsCRP level. Using multivariable Cox proportional hazard models, we determined the association of longitudinal follow-up hsCRP with MACE at 30 months among 8,563 patients (aged 64.6 ± 9 years, 22% women). Patients with incident MACE (n = 961) had higher baseline hsCRP levels (1.77 vs 1.46 mg/L, p <0.0001 for patients with and without MACE, respectively) and showed an upward trajectory during follow-up, whereas median hsCRP levels remained <2 mg/L at all time points (1.83 vs 1.53 mg/L, 1.91 vs 1.53 mg/L, 1.76 vs 1.37 mg/L, at 3, 12, and 24 months, respectively). In a multivariable analysis, higher longitudinal hsCRP levels were independently associated with MACE (hazard ratio [95% confidence interval] per SD 1.19 [1.10 to 1.29], p <0.001), the majority of its individual components and all-cause death. Multivariable models containing longitudinal hsCRP provided improved predictive ability of MACE over baseline hsCRP. In the setting of established medical therapies, longitudinal follow-up hsCRP was independently associated with long-term MACE. In conclusion, these findings suggest that longitudinal hsCRP represents a novel approach of residual cardiovascular risk even when on-treatment hsCRP levels remain <2 mg/L.
evacetrapibinflammationoutcomes trials
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.