scholarly journals The Prevalence and Diagnostic Ratio of Familial Hypercholesterolemia (FH) and Proportion of Acute Coronary Syndrome in Japanese FH Patients in a Healthcare Record Database Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Tamio Teramoto ◽  
Tomohiro Sawa ◽  
Satoshi Iimuro ◽  
Hyoe Inomata ◽  
Takashi Koshimizu ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Familial Hypercholesterolemia ◽  
Index Date ◽  
Genetic Disorder ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Lipid Lowering ◽  
Diagnostic Ratios ◽  
Coronary Syndrome ◽  
Electronic Healthcare Databases

Background. Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). Because of underdiagnosis, acute coronary syndrome (ACS) is often the first clinical manifestation of FH. In Japan, there are few reports on the prevalence and diagnostic ratios of FH and the proportion of ACS among FH patients in clinical settings. Methods. This retrospective, observational study used anonymized data from electronic healthcare databases between April 2001 and March 2015 of patients who had ≥2 LDL-C measurements recorded after April 2009. The index date was defined as the date of the first LDL-C measurement after April 2009. The primary endpoint was the prevalence of definite or suspected FH; secondary endpoints included the proportion of FH patients hospitalized for ACS, the proportion of patients using lipid-lowering drugs (LLDs), and LDL-C levels. Results. Of the 187,781 patients screened, 1547 had definite or suspected FH (0.8%) based on data from the entire period; 832 patients with definite (n=299, 0.16%) or suspected FH (n=533, 0.28%) before the index date were identified in the main analysis cohort. LLDs were used in 214 definite FH patients (71.6%) and 137 suspected FH patients (25.7%). Among definite or suspected FH patients with ACS (n=84) and without ACS (n=748), 32.1% and 30.1% with definite FH and 3.2% and 2.4% with suspected FH had LDL-C levels<2.6 mmol/L (<100 mg/dL), respectively. Sixty patients (7.2%) were hospitalized due to ACS at the index date. Conclusions. The prevalence of FH in this Japanese cohort of patients with ≥2 LDL-C measurements at hospitals was 0.8%, which is higher than that currently reported in epidemiological studies (0.2–0.5%). Patients with suspected FH, with or without ACS, had poorly controlled LDL-C levels and were undertreated. The proportion of FH patients who were hospitalized due to ACS was 7.2%.

P944Comparing therapeutic gap in lipid-lowering management between high-risk cardiovascular patients after acute coronary syndrome, stroke and critical limb ischemia

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B P Y Yan ◽  
C K Y Chan ◽  
W H S Lai ◽  
O T L To
Keyword(s):  
Acute Coronary Syndrome ◽  
Critical Limb Ischemia ◽  
Goal Attainment ◽  
Density Lipoprotein ◽  
Limb Ischemia ◽  
Lipid Lowering ◽  
Stroke Patients ◽  
High Potency ◽  
Coronary Syndrome ◽  
Risk Patients

Abstract Background Guidelines recommend intensive low-density-lipoprotein cholesterol (LDL-C) lowering in high cardiovascular (CV) risk patients with acute coronary syndrome (ACS), stroke and critical limb ischemia (CLI). Purpose We evaluated LDL-C goal attainment and lipid-lowering treatment (LLT) in a Chinese population with ACS, stroke and CLI patients. Methods We retrospectively evaluated consecutive high CV risk patients discharged between 2013 and 2017 from 3 hospitals in Hong Kong. Lipid profile and LLT were compared among 3 patient groups: ACS, Stroke and CLI. Results Of 10,168 high-CV risk patients (mean age 70.6±13.7 years; 62.4% male), 64.0% were ACS, 33.6% stroke and 2.5% CLI. Between baseline and 12-month, mean LDL-C reduced from 2.7±1.1 to 2.0±0.8 mmol/L in ACS patients, 2.7±1.0 to 2.0±0.7 mmol/L in stroke patients and 2.5±1.0 to 2.2±0.9 mmol/L in CLI patients (p<0.01). Proportion of CLI patients (29.9%) who achieved target LDL-C <1.8mmol/L at month 12 was significantly lower than stroke (45.6%) and ACS (48.2%) patients (p<0.01). The mean residual distance to target LDL-C was greatest in CLI (0.8±0.8 mmol/L) compared to stroke (0.6±0.6 mmol/L) and ACS (0.7±0.7 mmol/L) patients (p<0.01). Use of statin therapy on discharge was highest in ACS (88.4%) compared to stroke (78.3%) and CLI (52.6%) patients (p<0.01). But use of high-potency statin (rosuvastatin ≥20mg, atorvastatin ≥40mg or simvastatin ≥80mg) on discharge was very low in stroke (3.0%) and CLI (2.0%) compared to ACS (21.4%, p<0.01) patients. At 12 months 28.8% ACS, 34.3% stroke and 51.4% CLI patients were on no LLT (p<0.01) and the use of high-potency statin did not change significantly (3.0% in stroke, p=0.99; and 1.2% in CLI, p=0.48). Despite the poor achievement in LDL-C target in CLI patients, the proportion of CLI patients switching to high-potency statin (0.8%) was significantly lower than stroke (1.3%) and ACS (5.2%) patients (p<0.01). Conclusion This study demonstrated significant therapeutic gaps in lipid-lowering management in high CV risk patients. In particular, CLI patients were less aggressively treated with LLT and hence larger proportion of patient not achieving LDL-C target compared to ACS and stroke patients.

Low-density lipoprotein cholesterol target attainment in patients with stable or acute coronary heart disease in the Asia-Pacific region: results from the Dyslipidemia International Study II

2018 ◽  
Vol 25 (18) ◽  
pp. 1950-1963 ◽  
Author(s):  
Kian-Keong Poh ◽  
Baishali Ambegaonkar ◽  
Carl A Baxter ◽  
Philippe Brudi ◽  
Wacin Buddhari ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Acute Coronary Syndrome ◽  
Heart Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome

Background As mortality due to cardiovascular disease increases throughout the world, accurate data on risk factors such as hyperlipidemia are required. This is lacking in the Asia-Pacific region. Design The observational Dyslipidemia International Study (DYSIS) II was established to quantify the extent of hyperlipidemia in adults with acute and stable coronary heart disease globally. Methods Patients with stable coronary heart disease or hospitalised with an acute coronary syndrome were enrolled across nine Asia-Pacific countries from July 2013 to October 2014. Lipid-lowering therapy and low-density lipoprotein cholesterol target attainment (<70 mg/dL) were assessed. The acute coronary syndrome cohort was followed up 4 months post-discharge. Results Of the 4592 patients enrolled, 2794 had stable coronary heart disease and 1798 were admitted with an acute coronary syndrome. In the coronary heart disease cohort, the mean low-density lipoprotein cholesterol level was 86.9 mg/dL, with 91.7% using lipid-lowering therapy and 31% achieving low-density lipoprotein cholesterol of less than 70 mg/dL. In the acute coronary syndrome cohort at admission, the corresponding values were 103.2 mg/dL, 63.4% and 23.0%, respectively. Target attainment was significantly higher in lipid-lowering therapy-treated than non-treated patients in each cohort (32.6% vs. 12.9% and 31.1% vs. 9.0%, respectively). Mean atorvastatin-equivalent dosages were low (20 ± 15 and 22 ± 18 mg/day, respectively), with little use of non-statin adjuvants (13.0% and 6.8%, respectively). Low-density lipoprotein cholesterol target attainment had improved by follow-up for the acute coronary syndrome patients, but remained low (41.7%). Conclusions Many patients in Asia at very high risk of recurrent cardiovascular events had a low-density lipoprotein cholesterol level above the recommended target. Although lipid-lowering therapy was common, it was not used to its full potential.

Abstract 17824: Gemcabene and Atorvastatin Alone and Combined Markedly Reduce LDL-C in LDL Receptor-deficient Mice, a Model of Homozygous Familial Hypercholesterolemia

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Charles L Bisgaier ◽  
Bruce J Auerbach
Keyword(s):  
Total Cholesterol ◽  
Familial Hypercholesterolemia ◽  
Genetic Disorder ◽  
Density Lipoprotein ◽  
Standard Of Care ◽  
Rat Hepatocytes ◽  
Lipid Lowering ◽  
Homozygous Familial Hypercholesterolemia ◽  
Deficient Mice

Background: Gemcabene (Gem) is a late-stage Phase 2 clinical candidate being evaluated for the reduction of low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemia (HoFH) patients. Combination therapy includes statins as standard of care to treat this genetic disorder. LDL-deficient (LDLr) mice have been widely used with lipid-lowering agents to demonstrate LDL-C lowering with good translation to clinical efficacy. We have previously shown that atorvastatin (Atorva) reduces LDL-C and apoB in the LDLr deficient mice and in casein-fed (endogenous hypercholesterolemic) rabbits. Experiment and Results: In the current study, we assessed Gem and Atorva effects alone and in combination on reduction of LDL-C in chow-fed LDLr deficient mice, an animal model of HoFH. Baseline LDL-C and total cholesterol were 246±20 mg/dL and 329±23 mg/dL in these mice Female LDLr deficient mice (n=10) were treated with Atorva alone (60mg/kg/day), Gem alone (60/mg/kg/day) or the agents combined (Atorva + Gem)(each at 60 mg/kg/day) for 14 days. Following treatments with Atorva, Gem, and Atorva+Gem, fasting LDL-C reduced by 22%, 55% and 72%, respectively, and total cholesterol by 21%, 47%, and 58%, respectively; showing additional reduction of 50% LDL-C by Gem on top of Atorva alone. Since LDLr are absent in these mice, similar to HoFH patients, the LDL-C lowering by Gem could be due to reduced VLDL production rates. Indeed, our studies in rat hepatocytes and in apoB100-only mice (apobec-1 knockout) showed reduced radioactivity in cholesterol and triglyceride fractions in the hepatocytes and in the plasma and liver of mice administered 14C acetate, suggesting cholesterol and fatty acid synthesis inhibition as a mechanism of LDL-C lowering. Gem also enhances the clearance of VLDL in normal rats. We propose both mechanisms may contribute to LDL-C reduction in LDLr deficient mice. A more detailed kinetic study of Gem in LDLr deficient models is underway to verify these proposed mechanisms. Conclusions: Gemcabene alone and combined with atorvastatin significantly (55-72%) reduced LDL-C in this predictive in-vivo HoFH disease model. These findings suggest that treatment with Gem on top of standard of care therapy by statins may benefit HoFH patients.

P641Patient characteristics and treatment patterns in patients on lipid-lowering therapies following an acute coronary syndrome in France

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Bruckert ◽  
G Desamericq ◽  
A Khachatryan ◽  
P Ngo ◽  
G Gusto ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
High Intensity ◽  
Density Lipoprotein ◽  
Treatment Patterns ◽  
Lipid Lowering ◽  
Moderate Intensity ◽  
Treatment Intensity ◽  
Coronary Syndrome ◽  
Low Intensity

Abstract Background introduction Many patients, especially those at very high cardiovascular (CV) risk, do not reach low-density lipoprotein cholesterol (LDL-C) targets for at least 2 reasons: they may not receive a sufficiently intensive regimen, and/or they may not adhere to their medication. Purpose Describe demographic, clinical characteristics and treatment intensity and adherence in patients on lipid lowering therapies (LLT) following an Acute Coronary Syndrome (ACS) in France. Methods Retrospective cohort study on the PGRx (the Pharmacoepidemiologic General Research eXtension program)-ACS dataset in France, with data collected retrospective and prospectively via physicians, prescription records and patient interviews. Patients were accrued prospectively and/or retrospectively by centres from the PGRx Cardiology and General Practitioners networks. We included adult patients (≥18 years) suffering an ACS between 2013 and 2016 who received LLT at or within 92 days of their ACS hospital discharge. Follow-up was censored at time of new CV event, death, lost to follow-up or interview date (mean duration 12.4 months). Outcomes of interest included LLT intensity (high, moderate and low intensity statins with or without ezetimibe) and adherence measured as proportion of days covered (PDC). Results 2695 eligible patients were included (77% men); mean age (SD) 63.1 (12.8), 18% had diabetes mellitus, mean (SD) LDL-C 112.1 (46.4) mg/dl. Treatment with LLT at discharge is summarised in table below. Age and baseline LDL-C were drivers of treatment intensity with higher proportion of patients on high intensity statins in younger patients and in those with higher baseline LDL-C. Overall 70% of patients were adherent (PDC≥80%). Patients on moderate intensity were more adherent (76%) than those on low (63%) or high intensity statins (67%). Treatment patterns with LLT after an ACS LLT following ACS N (%) PDC at 1 year, Mean (SD) Adherent, N (%) Not Adherent, N (%) Ezetimibe 34 (1.3%) 82.8% (31.3%) 26 (76.5%) 8 (23.5%) Low intensity statins 64 (2.4%) 74.8% (33.8%) 40 (62.5%) 24 (37.5%) Moderate intensity statins 993 (37.1%) 82.0% (30.9%) 751 (75.6%) 242 (24.4%) High intensity statins 1515 (56.6%) 74.6% (36.2%) 1007 (66.5%) 508 (33.5%) Statin + ezetimibe 59 (2.2%) 75.9% (34.7%) 40 (67.8%) 19 (32.2%) Overall 2695 (100%) 77.6% (34.3%) 1871 (69.9%) 807 (30.1%) Conclusion(s) Our data show a substantial proportion of patients in France are not treated with high intensity statins after an ACS despite guidelines recommendation. Adherence to LLT is acceptable in patients after an ACS although it appears to worsen when high intense statins are used Acknowledgement/Funding Study has been funded by Amgen GmbH

scholarly journals Long-term use of a combination of atorvastatin and ezetimibe in children with homozygous familial hypercholesterolemia

2017 ◽  
Vol 5 (1) ◽  
pp. 275
Author(s):  
Devi Dayal ◽  
Keerthivasan Seetharaman ◽  
Savita Bhunwal ◽  
Nimisha Jain
Keyword(s):  
Familial Hypercholesterolemia ◽  
Genetic Disorder ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Homozygous Familial Hypercholesterolemia ◽  
Limited Data ◽  
Low Density Lipoprotein Cholesterol

Background: Homozygous familial hypercholesterolemia (HoFH) is an underdiagnosed and undertreated genetic disorder of lipoprotein metabolism associated with mortality during young age due to accelerated atherosclerosis. There is limited data on the efficacy of lipid lowering therapies in HoFH. Methods: Medical records of 3 children with HoFH who received a combination of atorvastatin and ezetimibe for a mean duration of 11.6±1.5 years were retrospectively analysed. Results: There was a significant decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) from the baseline levels (mean percent change in TC, LDL-C, TG and HDL-C of 58.5%, 56.2%, 67.5% and 29.7% respectively). Conclusions: We conclude that long-term use of a combination of atorvastatin and ezetimibe significantly lowers the plasma LDL-C concentrations in patients with HoFH without causing any significant adverse effects. Ours is the first study from India on long-term use of lipid modifying drug therapy in children with HoFH.

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