New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
Article information
Diabetes Metab J 2022;46:517-532. https://doi.org/10.4093/dmj.2022.0198
In this article Page 517, a part of abstract was corrected as follows:
Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha (PPARα) modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis.
In Page 521, a part of text was corrected as follows:
Nevertheless, considering that pemafibrate may prevent disease progression in non-alcoholic fatty liver disease (NAFLD) patients with hypertriglyceridemia, the possibility that of ASCVD risk reduction by pemafibrate in patients with NAFLD remains [57].
In Page 521-522, a part of text was corrected as follows:
The contrasting results for icosapent ethyl versus omega-3 carboxylic acids have led to a controversy focused on design differences between the comparator oils (placebos) in REDUCE-IT trial and STRENGTH. REDUCE-IT used mineral oil whereas STRENGTH used corn oil. Importantly, the REDUCE-IT investigators reported significant increases in LDL-C and CRP in the mineral oil group compared to icosapent ethyl-treated group [62]. That finding led to a cohort study, which was designed to mimic the REDUCE-IT trial; it showed that the contrasting CVD outcomes between the two trials could be partly explained by a difference in the effects of the comparator oils (mineral vs. corn), but not the active oils (EPA vs. EPA+DHA), on lipid traits and C-reactive protein [65]. Recently, a study of several ASCVD-related biomarkers in REDUCE-IT, conducted by the investigators themselves, showed that icosapent ethyl had minimal effects on those biomarkers, whereas levels increased among those allocated to mineral oil [66]. All together, these analyses suggest that the results of the REDUCE-IT trial must be interpreted with some caution.
In Page 524, heading was corrected from ‘IONIS-APO(a)Rx and IONIS-APO(a)LRx’ to ‘Apo(a) inhibitor’.
In Page 525, a part of text was added as follows:
Recently, the results of olpasiran, an siRNA to target LPA were reported. In a phase 1 trial involving participants with Lp(a) 70–199 nM or >200 nM, single doses of olpasiran at 3, 9, 30, 75, or 225 mg were administered. Plasma Lp(a) levels were reduced in a dose-responsive manner from 71% to 97%. Only one patient on olpasiran experienced an injection site reaction [118].
In addition, the results of SLN360, an siRNA to target LPA messenger RNA were reported. In a phase 1 trial involving participants with Lp(a) >60 mg/dL and no known CVD, single doses of SLN360 at 30, 100, 300, or 600 mg were administered. Plasma Lp(a) levels were reduced by 46% at a dose of 30 mg, 86% at 100 mg, 96% at 300 mg, and 98% at 600 mg, as compared with the 10% with the placebo. Low-grade injection site reactions and headache were common treatment-emergent adverse events [119].
In Page 525, a part of text was corrected as follows:
Indeed, few epidemiological studies showed increased mortality when plasma HDL-C was elevated [123,124]. In addition, RCTs with niacin and cholesteryl ester transfer protein inhibitors, in which HDL-C levels were significantly increased, failed to show a reduction in ASCVD risk [125,126].
In Page 525, a part of text was corrected as follows:
Lipid-free apoA1 triggers microsolubilization of cell membrane lipids, facilitating transfer of free cholesterol and phospholipids, after an interaction with the ATP-binding cassette transporter A1, to form nascent HDL particles [128,129]. These nascent HDL particles, after being remodeled by the lecithin cholesterol acyltransferase, transform into mature HDL particles. These mature HDL particles interact with the ATP-binding cassette transporter G1, ATPbinding cassette transporter G4, and scavenger receptor class B type 1 to mediate additional cholesterol efflux from the foam cells in the arterial wall [130,131].
In Page 526, a part of text was corrected as follows:
Pemafibrate, the first selective PPARα modulator, shows a favorable benefit-risk balance compared to fenofibrate in early phase trials but seems to have failed to reduce ASCVD in PROMINENT.
A corrected version of Fig. 1 and figure legend is attached.
A corrected version of Table 1 is attached. Olpasiran and SLN360 have been added in the table.
Majority of Corrigendum was done for clarifying the meaning of the sentence or paragraph. We apologize for any inconvenience that this may have caused.