The Effects of Lipid-Lowering Therapy on Serum Eicosapentaenoic Acid to Arachidonic Acid Ratio: An HIJ-PROPER Sub-Analysis

2020 ◽  
Vol 25 (6) ◽  
pp. 548-555
Author(s):  
Hiroyuki Arashi ◽  
Junichi Yamaguchi ◽  
Erisa Kawada-Watanabe ◽  
Hisao Otsuki ◽  
Haruki Sekiguchi ◽  
...  

Background: Controversy remains regarding the influence of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio. Objective: This study aimed to clarify the effects of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio in patients with acute coronary syndrome (ACS). Methods: This was a post hoc sub-analysis of the Heart Institute of Japan-PRoper level of lipid-lowering with pitavastatin and ezetimibe in ACS study. We compared the eicosapentaenoic acid/arachidonic acid ratio changes from baseline to the 3-month follow-up after contemporary lipid-lowering therapy with pitavastatin + ezetimibe therapy and pitavastatin mono-therapy. Results: Among patients with ACS and dyslipidemia, the eicosapentaenoic acid/arachidonic acid increased significantly in the pitavastatin mono-therapy group (0.40 ± 0.26 to 0.46 ± 0.34, P < .0001) but did not increase in the pitavastatin + ezetimibe group (0.37 ± 0.22 to 0.38 ± 0.27, P = .18). When the analysis was limited to patients who received 2 mg/day of pitavastatin during the follow-up period, these trends in changes of the eicosapentaenoic acid/arachidonic acid ratio remained unchanged. Multivariate analysis showed that ezetimibe use ( P = .005; β = 0.09), ST-elevation myocardial infarction ( P = .04; β = −0.01), and baseline low-density lipoprotein cholesterol (LDL-C) level ( P = .0003; β = 0.12) were independent predictors of the percentage change in the eicosapentaenoic acid/arachidonic acid ratio. These trends were similar even when the analysis was limited to patients who did not take statins at enrollment. Conclusion: Standard lipid-lowering therapy with pitavastatin mono-therapy improved the eicosapentaenoic acid/arachidonic acid ratio for patients with ACS. Intensive lipid-lowering therapy with pitavastatin + ezetimibe did not improve the eicosapentaenoic acid/arachidonic acid ratio, although LDL-C decreased significantly. Inhibition of the improvement in the eicosapentaenoic acid/arachidonic acid ratio by adding ezetimibe may affect cardiovascular disease prognosis.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Nakawaza ◽  
H Arashi ◽  
H Nomura ◽  
E Kawada-Watanabe ◽  
M Ogiso ◽  
...  

Abstract Background Polyunsaturated fatty acids, especially omega-3 and -6 series, are key essential nutrients that play an important role in humans to maintain cell membranes and function. A recent randomized trial reported that adding eicosapentaenoic acid (EPA) to statins was beneficial to cardiovascular disease patients who had a residual risk factor. Further, several studies have reported that the low baseline value for EPA to arachidonic acid (AA) ratio is related to worse clinical outcome and plaque vulnerability in coronary artery disease patients. However, effects of baseline EPA/AA ratio on clinical outcomes in ACS patients have not been thoroughly evaluated. Objectives This study aimed to examine the impact of baseline eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio on clinical outcomes of acute coronary syndrome (ACS) patients and how lipid-lowering therapy affects serum EPA/AA levels in these patients. Methods This is a sub-analysis of HIJ-PROPER assessing the effect of aggressive low-density lipoprotein cholesterol (LDL-C)-lowering treatment with pitavastatin+ezetimibe in 1,734 ACS patients with dyslipidemia. Patients were divided into two groups based on EPA/AA level on admission (cut-off: 0.34 μg/mL; median of baseline EPA/AA level) and clinical outcomes were examined. Results Percent reduction of LDL-C from baseline to follow-up and mean LDL-C level during follow-up were similar regardless of baseline EPA/AA ratio. In the low EPA/AA group, the Kaplan–Meier estimate for the primary endpoint at 3 years was 27.2% in the pitavastatin+ezetimibe group, compared with 36.6% in the pitavastatin-monotherapy group [hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.52–0.93; P=0.015). However, in the high EPA/AA group, there was no significant reduction in the primary endpoint by pitavastatin+ezetimibe therapy (HR, 0.92; 95% CI, 0.70–1.20; P=0.52). Conclusions Aggressive lipid-lowering therapy with ezetimibe had a positive effect on clinical outcomes in the low EPA/AA group of ACS patients with dyslipidemia, but not in the high EPA/AA group. This effect was independent of LDL-C reduction and suggests that EPA/AA measurement on admission in ACS patients contributes to a “personalized” lipid-lowering approach.


2013 ◽  
Vol 7 ◽  
pp. CMC.S11488 ◽  
Author(s):  
Calvin W Chin ◽  
F Gao ◽  
TT Le ◽  
RS Tan

Lipid goal attainment studies in Asian patients with acute coronary syndrome (ACS) are limited. The objectives of this study were to determine low-density lipoprotein cholesterol (LDL-C) goal attainment rate at 4 months, and to examine prescription behavior influencing lipid goal attainment in Asian patients with ACS. A retrospective analysis of 267 patients with ACS was performed. The mean follow-up duration was 41.2 ± 10.7 months. LDL-C goal attainment rate was highest at 4 months (36.7%) but declined progressively throughout follow-up. More than 85% of patients were discharged with equipotent statin dose of 2 (equivalent to simvastatin 20 mg) or less. In patients who did not attain LDL-C goals, the statin dose remained low throughout follow-up because of a lack in responsive dose titration. Aggressive lipid-lowering therapy should be initiated early to improve goal attainment in these high-risk patients.


2005 ◽  
Vol 39 (2) ◽  
pp. 329-334 ◽  
Author(s):  
Stacy A Lauderdale ◽  
Amy Heck Sheehan

OBJECTIVE: To describe current data evaluating the use of intensive lipid-lowering therapy in patients with coronary heart disease. DATA SOURCES: A literature search using MEDLINE (1966–September 2004) was conducted using the search terms lipoproteins, low-density lipoprotein cholesterol (LDL-C), hydroxymethylglutaryl-coenzyme A reductase inhibitors, coronary arteriosclerosis, and coronary disease to identify published trials comparing the effects of intensive and conventional lipid-lowering therapy. DATA SYNTHESIS: Intensive lipid-lowering therapy reduces LDL-C levels significantly more than conventional treatment and appears to reduce cardiovascular morbidity and mortality in patients who have recently experienced acute coronary syndrome (ACS). However, evidence suggesting clinical benefits in patients with stable coronary heart disease is currently lacking. CONCLUSIONS: Although data are limited, patients with ACS may benefit from intensive lipid-lowering therapy. Several studies are underway to determine the appropriate role of intensive lipid-lowering therapy.


2021 ◽  
Vol 4 (7) ◽  
pp. 01-06
Author(s):  
Anatoly Langer

Background: We compared the use of lipid lowering therapy, low density-lipoprotein cholesterol (LDL-C) levels, and proportion achieving guideline-recommended LDL-C levels in patients with private vs. public insurance coverage for their lipid lowering treatment. Materials and Methods: Guidelines Oriented Approach to Lipid lowering (GOAL) Canada enrolled 2009 patients with cardiovascular disease (CVD) or heterozygous familial hypercholesterolemia (FH) and an LDL-C above the guideline-recommended target of <2.0 mmol/L despite maximally tolerated statin therapy. During two follow-up visits physicians received online reminders of treatment recommendations. Results: Of 2009 patients enrolled (median age 63 years, 42% female), there were 1284 (64%) patients with private and 725 (36%) with public insurance for lipid lowering therapy. Patients with private insurance were younger and less likely to have a history of heart failure or to be on bile acid sequestrants. There was no difference between the groups in their lipid levels or lipid lowering therapy at baseline. During the follow up, there was no difference in the use of ezetimibe; however, the use of PCSK9i was more frequent in patients with private insurance (31.7 % vs. 21%, p<0.0001), the mean LDL-C level was slightly lower (2.11±1.17 vs. 2.31±1.17 mmol/L, p = 0.001), and the proportion of patients achieving the guideline-recommended LDL-C level was greater (54% vs. 45.5%, p = 0.001). After adjustment for other factors in a multivariable model, private insurance was not a significant predictor of achieving the guideline-recommended LDL-C level in a multivariable model. Conclusion: While PCSK9i use was higher in patients with private insurance, the majority of patients with either private or public insurance experienced similar treatment inertia. The cost of non-generic medications does not appear to be the dominant reason for the continued care gap in lipid lowering of high-risk patients.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Nakazawa ◽  
H Arashi ◽  
Y Inagaki ◽  
H Otsuki ◽  
J Yamaguchi ◽  
...  

Abstract Background This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events. Methods The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. For the present analysis, the entire cohort was divided into three groups according to HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, 43–53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and the incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups. Results The primary endpoint was reported in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively. The incidence of the primary endpoint was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19–1.9; p=0.001). Irrespective of the treatment regimen, Group 1 had a significantly higher rate of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12–2.22; p=0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05–1.98; p=0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles. Conclusions Lower levels of HDL-C at 3-month follow-up are associated with higher incidence of the cardiovascular events in patients with acute coronary syndrome receiving contemporary lipid-lowering therapy. HDL-C levels and Cardiovascular events Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 9 (8) ◽  
pp. 879-887
Author(s):  
Camille Buonvino ◽  
Romain Chopard ◽  
Benoît Guillon ◽  
Etienne Puymirat ◽  
Michel Farnier ◽  
...  

Aims To improve attainment of LDL-cholesterol (LDL-c) targets, an expert group proposed an algorithm for lipid-lowering therapy during hospitalization for acute coronary syndrome and during follow-up. We aimed to assess adherence to this algorithm, and evaluate its impact on LDL-c levels and on attainment of therapeutic LDL-c targets in a population of post-acute coronary syndrome patients. Methods and results Prospective, observational study including patients admitted for acute coronary syndrome between February 2017 and September 2018. Patients admitted without statins or ezetimibe were considered ‘naïve’. Baseline LDL-c was admission LDL-c in naïve patients, and for those taking lipid-lowering therapy at admission, baseline LDL-c was back-calculated. In line with the most recent guidelines, the target was a >50% reduction in naïve LDL-c and <55 mg/dL. In total, 270 patients were analysed, mean age 67 ± 12 years, 78% men, 26% diabetic. At admission, 175 (65%) were naïve, 95 (35%) had previous lipid-lowering therapy, of which 13 (5%) statin+ezetimibe. Average LDL-c at admission was 120 ± 47 mg/dL (136 ± 44 mg/dL in naïve, 91 ± 39 mg/dL in pretreated patients). Discharge prescription was in compliance with the algorithm in 204 (76%) patients. Average LDL-c at two months was 57 ± 28 mg/dL; it was <55 mg/dL in 135 (50%), and 178 (66%) achieved a >50% reduction. Overall, 125/270 (46%) achieved the LDL-c goal. The reduction in LDL-c observed at two months persisted at five months. Conclusion Prescription of high-intensity statins, associated with ezetimibe where applicable, achieves LDL-c levels <55 mg/dL in 50% of patients at two months, and attains therapeutic goals defined by the European Society of Cardiology in 46% of cases.


2016 ◽  
Vol 7 (6) ◽  
pp. 532-543 ◽  
Author(s):  
François Schiele ◽  
Michel Farnier ◽  
Michel Krempf ◽  
Eric Bruckert ◽  
Jean Ferrières ◽  
...  

In patients admitted for acute coronary syndrome (ACS), the guidelines of the European Society of Cardiology give a Class I, Level A recommendation for the prescription of high-intensity statins to be initiated as early as possible, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Although statins are widely prescribed after ACS, the intensity of therapy and the proportion of patients achieving target LDL-C values are often not in line with recommendations due to a lack of compliance with guidelines by the physicians, a lack of compliance with treatment or poor tolerance by patients, and poor dose adaptation. In this context, a group of French physicians came together to define strategies to facilitate and improve the management of lipid-lowering therapy after ACS. This paper outlines the scientific rationale for the use of statins at the acute phase of ACS, the utility of ezetimibe, the measurement of LDL-C during the course of ACS, the opportunities for detecting familial hypercholesterolaemia and the results of the consensus for the management of lipid-lowering therapy, illustrated in two decision-making algorithms.


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