Lipid-rich plaque density and low-density lipoprotein cholesterol in statin-treated versus statin-naive patients: a post hoc analysis of the LRP study.
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ABSTRACT:
SUBMITTER: Torguson R
PROVIDER: S-EPMC9903151 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Lipid-rich plaque density and low-density lipoprotein cholesterol in statin-treated versus statin-naïve patients: a post hoc analysis of the LRP study.
Torguson Rebecca R Mintz Gary S GS Zhang Cheng C Case Brian C BC Di Mario Carlo C Garcia-Garcia Hector M HM Waksman Ron R
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 20220501 1
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Project description:We aimed to evaluate the effect of baseline low-density lipoprotein cholesterol (LDL-C) on the outcomes of patients with the acute coronary syndrome (ACS) receiving pitavastatin monotherapy or the combination of pitavastatin + ezetimibe. In the HIJ-PROPER study, 1734 ACS patients with dyslipidemia were randomly assigned to receive pitavastatin or pitavastatin + ezetimibe therapy. Statin-naïve participants (n = 1429) were divided into two groups based on the median LDL-C level (131 mg/dL) at enrollment. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischemia-driven coronary revascularization. The median follow-up was 3.2 years. In the < 131 mg/dL group (n = 686), LDL-C changes were - 34.0% and - 49.8% in the pitavastatin monotherapy and pitavastatin + ezetimibe-treated groups (P < 0.0001), respectively; in the ≥ 131 mg/dL group (n = 743), LDL-C changes were - 42.9% and - 56.4% (P < 0.0001, respectively. Kaplan-Meier analyses revealed that the primary endpoint was not significantly different between the treatment groups for the < 131 mg/dL group, however, it was significantly lower in patients treated with pitavastatin + ezetimibe in the ≥ 131 mg/dL group (Hazard ratio = 0.72, 95% confidence interval = 0.56-0.91, P = 0.007, P value for interaction = 0.012). Statin-naïve ACS patients with baseline LDL-C < 131 mg/dL did not clinically benefit from pitavastatin + ezetimibe, while patients with baseline LDL-C ≥ 131 mg/dL treated with pitavastatin + ezetimibe showed better clinical results than those treated with pitavastatin monotherapy.Clinical Trial Registration: Original HIJ PROPER study; URL: http://www.umin.ac.jp/ctr . Unique Identifier; UMIN000002742, registered as an International Standard Randomized Controlled Trial.
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Project description:Low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for the development of atherosclerotic cardiovascular disease. Statins have been the gold standard for managing cholesterol levels and reducing the risks associated with atherosclerotic cardiovascular disease; however, many patients do not achieve their cholesterol goals or are unable to tolerate this drug class due to adverse drug events. Recent studies of non-statin cholesterol lowering drugs (i.e., ezetimibe, PCSK9 inhibitors) have demonstrated cardiovascular benefits; and new drugs [i.e., bempedoic acid (BDA), inclisiran] have produced promising results in pre-clinical and clinical outcome trials. This narrative review aims to discuss the place in therapy of ezetimibe, PCSK9 inhibitors, BDA, and inclisiran and describe their relative pharmacokinetic (PK) profiles, efficacy and safety as monotherapy and combination therapy, and cardiovascular benefit(s) when used for hypercholesterolemia.
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Project description:BackgroundCurrent evidence suggests a potential association between cerebral microbleeds (CMBs), low-density lipoprotein cholesterol (LDL-C) levels, and statin use, but the exact relationship remains unclear. This study aims to prospectively examine these relationships in a stroke-free population.MethodsFrom January 2010 to January 2020, we enrolled stroke-free individuals with at least one cerebral small vessel disease imaging marker from the CIRCLE study (ClinicalTrials.gov ID: NCT03542734). Participants underwent baseline and 1-year follow-up susceptibility-weighted imaging (SWI), and baseline LDL-C testing. New CMBs were categorized as strictly lobar and deep CMBs based on location.ResultsA total of 209 individuals were included. Baseline serum LDL-C levels were divided into quartiles: Q1 (≤1.76 mmol/L), Q2 (1.77-2.36 mmol/L), Q3 (2.37-2.93 mmol/L), and Q4 (>2.93 mmol/L). The incidence of new deep CMBs was 30.0%, 11.1%, 10.9%, 8.2% in Q1, Q2, Q3, Q4, respectively. Multivariate logistic model revealed that only LDL-C in Q1 was associated with increased incidence of new deep CMBs (OR = 4.256; 95% CI: 1.156-15.666; p = 0.029). In a subset of 169 participants without prior statin use, the use of atorvastatin was associated with reduced occurrence of new deep CMBs (OR = 0.181; 95% CI: 0.035-0.928; p = 0.040), while it was not found with rosuvastatin (OR = 0.808; 95% CI: 0.174-3.741; p = 0.785).ConclusionsWhile lower LDL-C levels were associated with higher CMB development, statin therapy did not increase the risk of new CMBs. Atorvastatin even demonstrated a protective effect.
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Project description:This study describes subsequent cardiovascular events and deaths by low-density lipoprotein cholesterol (LDL-C) level in patients with atherosclerotic cardiovascular disease (ASCVD) receiving moderate- to high-intensity statins. Olmsted County, Minnesota residents with index ASCVD (myocardial infarction, unstable angina, coronary revascularization, ischemic stroke or transient ischemic attack) occurring between 2005 and 2012 were identified, and those with a prescription for a moderate- or high-intensity statin and an LDL-C measurement in the 90 days after index were included. Cox regression models were used to examine associations between LDL-C, modeled as a time-dependent variable, and a composite outcome of subsequent cardiovascular events or all-cause death. Among 1,854 patients with ASCVD (mean [SD] age 66.0 [13.3] years, 63.6% male), a total of 1,241 events were observed from index ASCVD through follow-up (median of 5.9 years). The rate (95% confidence interval) per 100 person-years was 11.26 (10.64 to 11.91). Starting follow-up 90 days after index ASCVD event, the rates per 100 person-years were 10.51 (9.57 to 11.52), 9.57 (8.66 to 10.55), and 11.40 (9.96 to 12.98) for LDL-C <70, 70-<100 and ≥100 mg/dl, respectively. After adjustment for age, sex, and previous diagnoses of ASCVD, diabetes, hypertension, heart failure, and chronic kidney disease, the hazard ratio for cardiovascular event and/or death was significantly higher for patients with LDL-C ≥100 mg/dl than those with LDL-C <70 mg/dl (1.31 [1.08 to 1.59]). In conclusion, in patients with ASCVD, subsequent cardiovascular events occur at a high rate and the rates are highest in patients with LDL-C ≥100 mg/dl suggesting unmet treatment needs even in patients receiving moderate- to high-intensity statins.
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