Inflammatory and Cholesterol Risk in the FOURIER Trial

Abstract

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.

PCSK9 inhibition and inflammation: A narrative review

“…Considering hs-CRP mean changes were −0.2 mg/L in both treatment arms, the largest absolute CV risk decrement was found in patients with baseline hs-CRP > 3 mg/L. This post hoc analysis allows to identify individuals getting the largest benefit from PCSK9 antagonists; even in those achieving an on-treatment LDL-C of < 20 mg/dL there was a 3-year stepwise risk increment according to the baseline values of hs-CRP: +9% (hs-CRP < 1 mg/L), +10.8% (hs-CRP 1-3 mg/L) and +13.1% (hs-CRP > 3 mg/L) [104]. Moreover, event rates were lowest in patients achieving the lowest levels of both LDL-C and hs-CRP.…”

“…hypertension, diabetes mellitus, smoking, and renal dysfunction, and a higher rate of comorbid conditions, e.g. prior stroke and peripheral artery disease [104]. Briefly, in the FOURIER study, according to hs-CRP strata (< 1 mg/L, 1-3 mg/L and > 3 mg/L) hypertension was present in 76%, 81% and 84%, respectively; diabetes mellitus was found in 31%, 36% and 43%, respectively, and finally smoking was reported in 23%, 29% and 32%, respectively [104].…”

“…prior stroke and peripheral artery disease [104]. Briefly, in the FOURIER study, according to hs-CRP strata (< 1 mg/L, 1-3 mg/L and > 3 mg/L) hypertension was present in 76%, 81% and 84%, respectively; diabetes mellitus was found in 31%, 36% and 43%, respectively, and finally smoking was reported in 23%, 29% and 32%, respectively [104]. Thus, the use of a similar risk-stratification strategy with an even broader range of factors can ensure that PCSK9 inhibitors are made available to those who may benefit the most.…”

An updated review of lipid‐modifying therapy

“…Both evolocumab and alirocumab reduced CVD events in the presence of diabetes, but with no increase in new‐onset diabetes or worsening in glycaemia . Evolocumab reduced CVD events across all strata of the inflammatory marker high‐sensitivity C‐reactive protein …”

Understanding myocardial infarction

“…Over time, smooth muscle cells migrate from the media to the intima and lipid accumulates under a fibrous cap composed of vascular smooth muscle cells, elastin, and collagen. Furthermore, low-grade inflammation as epitomized by an elevated C-reactive protein, independent of LDL levels, has been shown to contribute to myocardial events and hence thought to contribute to the formation and progression of atherosclerotic disease 6 . As previously mentioned, inflammatory cells such as macrophages and T lymphocytes play a direct role in the formation and destabilization of atherosclerotic plaques.…”