Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.076
Claus Schmitt MD, Alberto Zambon MD, Christina Taylan MD, Joenna Driemeyer MD, Hofit Cohen MD, Paola Buonuomo MD, Abdullah Alashwal MD, Mohammed Al-Dubayee MD, José Diaz-Diaz MD, Faouzi Maatouk MD, Sergio Martinez-Hervas MDMD, Brian Mangal MSc, Naji Kholaif MD, Sandra Löwe MD, Zsuzsanna Tamas MD, Luis Masana MD
Background/Synopsis
Homozygous familial hypercholesterolemia (HoFH) is characterized by mutations in the low-density lipoprotein (LDL) receptor leading to highly elevated levels of LDL-cholesterol (LDL-C). As a result, patients with HoFH develop atherosclerotic cardiovascular disease in childhood and have a low life expectancy of ∼18 years without appropriate treatment. Diagnosis in early childhood is essential to reduce morbidity and mortality. Lomitapide is a selective microsomal triglyceride transfer protein inhibitor approved for adults with HoFH that works independently of the LDL receptor to lower LDL-C. APH-19 (NCT04681170) is the first clinical trial of lomitapide in pediatric patients with HoFH and met its primary endpoint (LDL-C reduction of -53.5% at Week 24; p<0.0001).
Objective/Purpose
We report additional parameters from APH-19 relating to the efficacy and safety of lomitapide in pediatric patients.
Methods
APH-19 is a phase 3, open-label, single-arm clinical trial in HoFH patients aged 5–17 years (N=43) consisting of a run-in period followed by 24-week efficacy and 80-week safety phases. Patients were stratified by age into three dose escalation groups, where the maximum doses were 20, 40 and 60 mg. Here, additional data at Week 24 of patient-level LDL-C reductions, lipoproteins (apolipoprotein B [ApoB] and lipoprotein A [Lp(a)]) and additional safety endpoints (growth/maturation and fat-soluble vitamin levels) are reported.
Results
Lomitapide treatment resulted in up to a 95% reduction of LDL-C from baseline at Week 24 with 53.5% of patients (n=23) having >50% reduction in LDL-C from baseline (Figure). Mean reduction in ApoB was -52.4% at Week 24 (p<0.0001); an ApoB subgroup analysis indicated general consistency across a range of parameters. Mean change from baseline in Lp(a) was -23.6% (p=0.0030) for nmol/L methodology and -11.3% (p=0.2884, Fisher Combined p-value p=0.0070) for mg/dL analysis. Subgroup results will be presented.
There were no clinically significant mean changes in weight or height from Baseline to Week 24. The mean change in weight-for-age Z-score was -0.371 for patients aged 5–10 years (11–17, N/A). Changes in height-for-age Z-score were -0.064 and -0.060 for patients aged 5–10 and 11–17 years, respectively. Fat-soluble vitamins at Week 24 were within normal range for individuals aged 5–17 years; vitamin E increased in 10.0% of patients aged 5–10 years, considered mild in severity.
Conclusions
These data further support the efficacy and safety of lomitapide across various parameters in pediatric patients. The lack of impact on patient maturation endpoints is encouraging; however, further long-term data are required.
{"title":"Lomitapide in Pediatric Patients with Homozygous Familial Hypercholesterolemia – Analysis of Secondary and Safety Endpoints from the APH-19 Study","authors":"Claus Schmitt MD, Alberto Zambon MD, Christina Taylan MD, Joenna Driemeyer MD, Hofit Cohen MD, Paola Buonuomo MD, Abdullah Alashwal MD, Mohammed Al-Dubayee MD, José Diaz-Diaz MD, Faouzi Maatouk MD, Sergio Martinez-Hervas MDMD, Brian Mangal MSc, Naji Kholaif MD, Sandra Löwe MD, Zsuzsanna Tamas MD, Luis Masana MD","doi":"10.1016/j.jacl.2024.04.076","DOIUrl":"10.1016/j.jacl.2024.04.076","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Homozygous familial hypercholesterolemia (HoFH) is characterized by mutations in the low-density lipoprotein (LDL) receptor leading to highly elevated levels of LDL-cholesterol (LDL-C). As a result, patients with HoFH develop atherosclerotic cardiovascular disease in childhood and have a low life expectancy of ∼18 years without appropriate treatment. Diagnosis in early childhood is essential to reduce morbidity and mortality. Lomitapide is a selective microsomal triglyceride transfer protein inhibitor approved for adults with HoFH that works independently of the LDL receptor to lower LDL-C. APH-19 (NCT04681170) is the first clinical trial of lomitapide in pediatric patients with HoFH and met its primary endpoint (LDL-C reduction of -53.5% at Week 24; p<0.0001).</p></div><div><h3>Objective/Purpose</h3><p>We report additional parameters from APH-19 relating to the efficacy and safety of lomitapide in pediatric patients.</p></div><div><h3>Methods</h3><p>APH-19 is a phase 3, open-label, single-arm clinical trial in HoFH patients aged 5–17 years (N=43) consisting of a run-in period followed by 24-week efficacy and 80-week safety phases. Patients were stratified by age into three dose escalation groups, where the maximum doses were 20, 40 and 60 mg. Here, additional data at Week 24 of patient-level LDL-C reductions, lipoproteins (apolipoprotein B [ApoB] and lipoprotein A [Lp(a)]) and additional safety endpoints (growth/maturation and fat-soluble vitamin levels) are reported.</p></div><div><h3>Results</h3><p>Lomitapide treatment resulted in up to a 95% reduction of LDL-C from baseline at Week 24 with 53.5% of patients (n=23) having >50% reduction in LDL-C from baseline (Figure). Mean reduction in ApoB was -52.4% at Week 24 (p<0.0001); an ApoB subgroup analysis indicated general consistency across a range of parameters. Mean change from baseline in Lp(a) was -23.6% (p=0.0030) for nmol/L methodology and -11.3% (p=0.2884, Fisher Combined p-value p=0.0070) for mg/dL analysis. Subgroup results will be presented.</p><p>There were no clinically significant mean changes in weight or height from Baseline to Week 24. The mean change in weight-for-age Z-score was -0.371 for patients aged 5–10 years (11–17, N/A). Changes in height-for-age Z-score were -0.064 and -0.060 for patients aged 5–10 and 11–17 years, respectively. Fat-soluble vitamins at Week 24 were within normal range for individuals aged 5–17 years; vitamin E increased in 10.0% of patients aged 5–10 years, considered mild in severity.</p></div><div><h3>Conclusions</h3><p>These data further support the efficacy and safety of lomitapide across various parameters in pediatric patients. The lack of impact on patient maturation endpoints is encouraging; however, further long-term data are required.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e545-e546"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.065
Mendel Roth PhD, Tiffany Haynes MD, Robert Fishberg MD, Loba Alam MD
<div><h3>Background/Synopsis</h3><p>Multifactorial chylomicronemia syndrome (MCS), also known as type V hyperlipoproteinemia, is a rare polygenic disorder characterized by severe hypertriglyceridemia. It is triggered by uncontrolled diabetes mellitus (DM), obesity, metabolic syndrome, and certain medications. It is not known whether hypertriglyceridemia associated with MCS accelerates atherosclerotic cardiovascular disease (ASCVD).</p></div><div><h3>Objective/Purpose</h3><p>To speculate the relationship between ASCVD in a patient with hypertriglyceridemia caused by MCS, uncontrolled DM, and polymorphic APOA5, APOE2/4, LMF1 and LP(a) intron mutations.</p></div><div><h3>Methods</h3><p>We present a 60-year-old male with PMH of severe hypertriglyceridemia (highest 6000mg/dL) with acute pancreatitis at age 40, CAD s/p CABG at age 50, PAD s/p bypass at age 57, HTN, mixed hyperlipidemia, uncontrolled DM, and family history of premature ASCVD. He was subsequently followed at the advanced lipid clinic where his medications included rosuvastatin, ezetimibe, evolocumab, fenofibrate, and icosapent ethyl. He underwent advanced genetic testing with GBinsight.</p></div><div><h3>Results</h3><p>GBinsight identified various polymorphic genes causing hypertriglyceridemia as follows:</p><p>APOA5 - c.*158C>T(rs2266788)</p><p></p><ul><li><span>-</span><span><p>This variant is found in ∼10% of the global population and has been associated with hypertriglyceridemia by multiple genome-wide association studies.</p></span></li></ul><p>APOA5 - c.457G>A(p.Val153Met)(rs3135507)</p><p></p><ul><li><span>-</span><span><p>This variant is found in ∼5-10% of the global population and has been associated with modest hypertriglyceridemia and lower HDL-C in the UKBiobank cohort.</p></span></li></ul><p>APOE2</p><p></p><ul><li><span>-</span><span><p>This allele has been associated with a reduction of the major lipolytic enzyme, lipoprotein lipase (LPL) activity, causing modest hypertriglyceridemia.</p></span></li></ul><p>LMF1 - p.Arg354Trp(rs143076454)</p><p></p><ul><li><span>-</span><span><p>This variant is found in ∼2% of the global population, and has been associated with a reduction of LPL activity causing modest hypertriglyceridemia.</p></span></li></ul><p>GBinsight identified various pathogenic genes causing elevated Lp(a) as follows:</p><p>LPA - Heterozygous for intron c.3947+467T>C(rs10455872)</p><p></p><ul><li><span>-</span><span><p>This variant serves a genetic proxy for short isoforms and is strongly associated with increased Lp(a), total and LDL-cholesterol levels, and increased ASCVD risk.</p></span></li></ul><p>APOE4</p><p></p><ul><li><span>-</span><span><p>This allele is associated with increased Lp(a) levels.</p></span></li></ul></div><div><h3>Conclusions</h3><p>We speculate that the combination of these polymorphisms works together to increase risk of severe hypertriglyceridemia, also known as MCS. Several smaller studies have suggested MCS is caused by either
{"title":"Accelerated Atherosclerosis in a Patient With Multifactorial Chylomicronemia Syndrome (MCS), Elevated Lp(a), APOE2/4 Genotype and Diabetes Mellitus.","authors":"Mendel Roth PhD, Tiffany Haynes MD, Robert Fishberg MD, Loba Alam MD","doi":"10.1016/j.jacl.2024.04.065","DOIUrl":"10.1016/j.jacl.2024.04.065","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Multifactorial chylomicronemia syndrome (MCS), also known as type V hyperlipoproteinemia, is a rare polygenic disorder characterized by severe hypertriglyceridemia. It is triggered by uncontrolled diabetes mellitus (DM), obesity, metabolic syndrome, and certain medications. It is not known whether hypertriglyceridemia associated with MCS accelerates atherosclerotic cardiovascular disease (ASCVD).</p></div><div><h3>Objective/Purpose</h3><p>To speculate the relationship between ASCVD in a patient with hypertriglyceridemia caused by MCS, uncontrolled DM, and polymorphic APOA5, APOE2/4, LMF1 and LP(a) intron mutations.</p></div><div><h3>Methods</h3><p>We present a 60-year-old male with PMH of severe hypertriglyceridemia (highest 6000mg/dL) with acute pancreatitis at age 40, CAD s/p CABG at age 50, PAD s/p bypass at age 57, HTN, mixed hyperlipidemia, uncontrolled DM, and family history of premature ASCVD. He was subsequently followed at the advanced lipid clinic where his medications included rosuvastatin, ezetimibe, evolocumab, fenofibrate, and icosapent ethyl. He underwent advanced genetic testing with GBinsight.</p></div><div><h3>Results</h3><p>GBinsight identified various polymorphic genes causing hypertriglyceridemia as follows:</p><p>APOA5 - c.*158C>T(rs2266788)</p><p></p><ul><li><span>-</span><span><p>This variant is found in ∼10% of the global population and has been associated with hypertriglyceridemia by multiple genome-wide association studies.</p></span></li></ul><p>APOA5 - c.457G>A(p.Val153Met)(rs3135507)</p><p></p><ul><li><span>-</span><span><p>This variant is found in ∼5-10% of the global population and has been associated with modest hypertriglyceridemia and lower HDL-C in the UKBiobank cohort.</p></span></li></ul><p>APOE2</p><p></p><ul><li><span>-</span><span><p>This allele has been associated with a reduction of the major lipolytic enzyme, lipoprotein lipase (LPL) activity, causing modest hypertriglyceridemia.</p></span></li></ul><p>LMF1 - p.Arg354Trp(rs143076454)</p><p></p><ul><li><span>-</span><span><p>This variant is found in ∼2% of the global population, and has been associated with a reduction of LPL activity causing modest hypertriglyceridemia.</p></span></li></ul><p>GBinsight identified various pathogenic genes causing elevated Lp(a) as follows:</p><p>LPA - Heterozygous for intron c.3947+467T>C(rs10455872)</p><p></p><ul><li><span>-</span><span><p>This variant serves a genetic proxy for short isoforms and is strongly associated with increased Lp(a), total and LDL-cholesterol levels, and increased ASCVD risk.</p></span></li></ul><p>APOE4</p><p></p><ul><li><span>-</span><span><p>This allele is associated with increased Lp(a) levels.</p></span></li></ul></div><div><h3>Conclusions</h3><p>We speculate that the combination of these polymorphisms works together to increase risk of severe hypertriglyceridemia, also known as MCS. Several smaller studies have suggested MCS is caused by either ","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Page e538"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.028
Samuel Kim MD, Amrita Krishnamurthy MD
<div><h3>Background/Synopsis</h3><p>A 72-year-old woman presents with pruritis, jaundice, skin lesions, blurred vision, and facial droop. Blood work reveals a total bilirubin of 21.5 mg/dL (15.4 mg/dL direct, 6.1 mg/dL indirect), AST 388 U/L, ALT 444 U/L, alkaline phosphatase 1,900 U/L, sodium 119 mmol/L, total cholesterol >1350 mg/dL, HDL 7 mg/dL, and triglycerides 306 mg/dL; LDL cannot be calculated. Brain magnetic resonance imaging demonstrates no acute pathology. Viral and autoimmune serologies are negative. Magnetic resonance cholangiopancreatography demonstrates no biliary pathology.</p><p>She reports drinking various herbal tea preparations along with an unknown supplement she purchased on television. A liver biopsy demonstrates bile duct injury and centrilobular cholestasis most consistent with drug-induced liver injury. She is treated with ursodiol and bile acid sequestrants however has ongoing symptoms. Her serum viscosity level is elevated and additional testing detects lipoprotein X. She is treated with three rounds of plasma exchange with normalization of her sodium level, resolution of xanthomas and neurologic symptoms, and marked improvement in her lipid panel.</p></div><div><h3>Objective/Purpose</h3><p>Recognize sequelae of lipoprotein X accumulation including pseudohyponatremia, xanthomas, and hyperviscosity. Discuss multidisciplinary management of lipoprotein X-induced hyperlipidemia.</p></div><div><h3>Methods</h3><p>Clinical case management at a tertiary care lipid program.</p></div><div><h3>Results</h3><p>Lipoprotein-X induced hyperlipidemia is a rare lipoprotein disorder. The most common etiologies are cholestatic liver disease, lecithin:cholesterol acyltransferase (LCAT) deficiency, liver graft-versus-host disease, and lipid infusions. With cholestasis, bile excretion and synthesis are inhibited to prevent bile-induced hepatotoxicity. This results in lack of cholesterol excretion into bile and free cholesterol release into blood, where it merges with phospholipids, albumin, and apolipoproteins C and E, to form lipoprotein X. As lipoprotein X does not contain apolipoprotein B, it does not undergo hepatic clearance and its levels are not affected by lipid-lowering therapies such as statins. Lipoprotein X has a similar density to LDL and can lead to false elevations in LDL on standard lipid panels, therefore lipoprotein electrophoresis can be used to detect lipoprotein X.</p><p>Hyperlipidemia induced by lipoprotein X accumulation can lead to numerous clinical sequelae including xanthomas, pseudohyponatremia, and hyperviscosity syndrome with associated neurologic symptoms. The mainstay of therapy is treatment of the underlying cholestatic disorder, however with refractory symptoms therapeutic plasma exchange can provide rapid lipoprotein clearance.</p></div><div><h3>Conclusions</h3><p>Due to lack of LDL receptor-mediated hepatic clearance, traditional lipid-lowering therapies do not have a role in the management of lipoprotei
背景/简介一名 72 岁的妇女出现瘙痒、黄疸、皮肤损伤、视力模糊和面部下垂。血常规显示总胆红素 21.5 mg/dL（直接胆红素 15.4 mg/dL，间接胆红素 6.1 mg/dL），谷草转氨酶 388 U/L，谷丙转氨酶 444 U/L，碱性磷酸酶 1,900 U/L，钠 119 mmol/L，总胆固醇 1350 mg/dL，高密度脂蛋白 7 mg/dL，甘油三酯 306 mg/dL；低密度脂蛋白无法计算。脑磁共振成像显示没有急性病变。病毒和自身免疫血清检查均为阴性。磁共振胰胆管造影显示没有胆道病变。她说自己喝了各种草药茶制剂，还在电视上购买了一种不知名的保健品。肝活检显示胆管损伤和中心叶胆汁淤积与药物性肝损伤最为一致。她接受了乌索地尔和胆汁酸螯合剂治疗，但症状仍在持续。她接受了三轮血浆置换治疗，血钠水平恢复正常，黄疽和神经系统症状缓解，血脂也明显改善。目标/目的认识脂蛋白 X 累积的后遗症，包括假性高钠血症、黄疽和高粘滞性。讨论脂蛋白 X 诱导的高脂血症的多学科治疗方法。结果脂蛋白 X 诱导的高脂血症是一种罕见的脂蛋白疾病。最常见的病因是胆汁淤积性肝病、卵磷脂：胆固醇酰基转移酶（LCAT）缺乏症、肝脏移植物抗宿主疾病和脂质输注。胆汁淤积症会抑制胆汁的排泄和合成，以防止胆汁引起的肝中毒。由于脂蛋白 X 不含载脂蛋白 B，因此不会被肝脏清除，其水平也不会受到他汀类药物等降脂疗法的影响。脂蛋白 X 的密度与低密度脂蛋白相似，可导致标准血脂检查中低密度脂蛋白的假性升高，因此脂蛋白电泳可用于检测脂蛋白 X。脂蛋白 X 累积引起的高脂血症可导致许多临床后遗症，包括黄疽、假性高钠血症和伴有神经症状的高粘滞综合征。结论由于缺乏低密度脂蛋白受体介导的肝脏清除，传统的降脂疗法在脂蛋白 X 诱导的高脂血症的治疗中没有作用。当治疗胆汁淤积性疾病后症状仍持续存在时，可利用治疗性血浆置换来清除脂蛋白。
{"title":"Multidisciplinary Management of Lipoprotein X-Induced Hyperlipidemia Secondary to Drug-Induced Liver Injury","authors":"Samuel Kim MD, Amrita Krishnamurthy MD","doi":"10.1016/j.jacl.2024.04.028","DOIUrl":"10.1016/j.jacl.2024.04.028","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>A 72-year-old woman presents with pruritis, jaundice, skin lesions, blurred vision, and facial droop. Blood work reveals a total bilirubin of 21.5 mg/dL (15.4 mg/dL direct, 6.1 mg/dL indirect), AST 388 U/L, ALT 444 U/L, alkaline phosphatase 1,900 U/L, sodium 119 mmol/L, total cholesterol >1350 mg/dL, HDL 7 mg/dL, and triglycerides 306 mg/dL; LDL cannot be calculated. Brain magnetic resonance imaging demonstrates no acute pathology. Viral and autoimmune serologies are negative. Magnetic resonance cholangiopancreatography demonstrates no biliary pathology.</p><p>She reports drinking various herbal tea preparations along with an unknown supplement she purchased on television. A liver biopsy demonstrates bile duct injury and centrilobular cholestasis most consistent with drug-induced liver injury. She is treated with ursodiol and bile acid sequestrants however has ongoing symptoms. Her serum viscosity level is elevated and additional testing detects lipoprotein X. She is treated with three rounds of plasma exchange with normalization of her sodium level, resolution of xanthomas and neurologic symptoms, and marked improvement in her lipid panel.</p></div><div><h3>Objective/Purpose</h3><p>Recognize sequelae of lipoprotein X accumulation including pseudohyponatremia, xanthomas, and hyperviscosity. Discuss multidisciplinary management of lipoprotein X-induced hyperlipidemia.</p></div><div><h3>Methods</h3><p>Clinical case management at a tertiary care lipid program.</p></div><div><h3>Results</h3><p>Lipoprotein-X induced hyperlipidemia is a rare lipoprotein disorder. The most common etiologies are cholestatic liver disease, lecithin:cholesterol acyltransferase (LCAT) deficiency, liver graft-versus-host disease, and lipid infusions. With cholestasis, bile excretion and synthesis are inhibited to prevent bile-induced hepatotoxicity. This results in lack of cholesterol excretion into bile and free cholesterol release into blood, where it merges with phospholipids, albumin, and apolipoproteins C and E, to form lipoprotein X. As lipoprotein X does not contain apolipoprotein B, it does not undergo hepatic clearance and its levels are not affected by lipid-lowering therapies such as statins. Lipoprotein X has a similar density to LDL and can lead to false elevations in LDL on standard lipid panels, therefore lipoprotein electrophoresis can be used to detect lipoprotein X.</p><p>Hyperlipidemia induced by lipoprotein X accumulation can lead to numerous clinical sequelae including xanthomas, pseudohyponatremia, and hyperviscosity syndrome with associated neurologic symptoms. The mainstay of therapy is treatment of the underlying cholestatic disorder, however with refractory symptoms therapeutic plasma exchange can provide rapid lipoprotein clearance.</p></div><div><h3>Conclusions</h3><p>Due to lack of LDL receptor-mediated hepatic clearance, traditional lipid-lowering therapies do not have a role in the management of lipoprotei","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e502-e503"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.060
Chris Yang MD, Ugochukwu Egolum MD, Riaz Mahmood DO
Background/Synopsis
Cardiac catheterization remains the gold standard for the evaluation of obstructive coronary artery disease in patients presenting with acute coronary syndrome (ACS). Although this procedure is lifesaving, there are several potential life-threatening complications such as coronary artery dissection. The impact of familial hypercholesterolemia (FH) on complication rates in patients presenting with acute coronary syndrome has not been well studied.
Objective/Purpose
The purpose of this study was to assess the impact of familial hypercholesterolemia on the development of coronary artery dissection in patients presenting with ACS undergoing percutaneous coronary intervention (PCI).
Methods
We performed a retrospective analysis of the NIS database from 2016 to 2018 to identify patients presenting with ACS and PCI using ICD-10-CM/PCS codes. We compared the primary outcome of coronary artery dissection in patients with and without familial hypercholesterolemia. The primary outcome was in-hospital mortality, and secondary outcomes were hypertension, acute kidney injury, cardiogenic shock, obesity, type 2 diabetes mellitus, length of stay, and total hospitalization cost. We performed multivariate logistic regression analysis to identify associations for coronary artery dissection.
Results
A total of 58,685 patients presented to the hospital with ACS and underwent PCI. The mean age was 64.85 ± 12.70 years, and most patients were male (69.69%) and Caucasian (75.51%). Patients with familial hypercholesterolemia (FH) had a higher coronary artery dissection rate at 2.27% vs. 1.22%, p = 0.52. There was a difference between patients with and without FH for in-hospital mortality, 0% compared to 4.40%, but not statistically significant (p = 0.15). The length of stay was longer for patients without FH, 4.45 days compared to 3.93 days (p = 0.38). Multiple logistic regression analysis revealed that type 2 diabetes was not a statistically significant predictor of coronary artery dissection, Table 1.
Conclusions
The presence of familial hypercholesterolemia was not a statistically significant predictor of coronary artery dissection, but cardiogenic shock was statistically significant. Further pragmatic clinical trials are needed to evaluate familial hypercholesterolemia and association with complications in patients presenting with acute coronary syndrome.
{"title":"Impact of Familial Hypercholesterolemia on Coronary Artery Dissection in Patients Undergoing Percutaneous Coronary Intervention (PCI)","authors":"Chris Yang MD, Ugochukwu Egolum MD, Riaz Mahmood DO","doi":"10.1016/j.jacl.2024.04.060","DOIUrl":"10.1016/j.jacl.2024.04.060","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Cardiac catheterization remains the gold standard for the evaluation of obstructive coronary artery disease in patients presenting with acute coronary syndrome (ACS). Although this procedure is lifesaving, there are several potential life-threatening complications such as coronary artery dissection. The impact of familial hypercholesterolemia (FH) on complication rates in patients presenting with acute coronary syndrome has not been well studied.</p></div><div><h3>Objective/Purpose</h3><p>The purpose of this study was to assess the impact of familial hypercholesterolemia on the development of coronary artery dissection in patients presenting with ACS undergoing percutaneous coronary intervention (PCI).</p></div><div><h3>Methods</h3><p>We performed a retrospective analysis of the NIS database from 2016 to 2018 to identify patients presenting with ACS and PCI using ICD-10-CM/PCS codes. We compared the primary outcome of coronary artery dissection in patients with and without familial hypercholesterolemia. The primary outcome was in-hospital mortality, and secondary outcomes were hypertension, acute kidney injury, cardiogenic shock, obesity, type 2 diabetes mellitus, length of stay, and total hospitalization cost. We performed multivariate logistic regression analysis to identify associations for coronary artery dissection.</p></div><div><h3>Results</h3><p>A total of 58,685 patients presented to the hospital with ACS and underwent PCI. The mean age was 64.85 ± 12.70 years, and most patients were male (69.69%) and Caucasian (75.51%). Patients with familial hypercholesterolemia (FH) had a higher coronary artery dissection rate at 2.27% vs. 1.22%, p = 0.52. There was a difference between patients with and without FH for in-hospital mortality, 0% compared to 4.40%, but not statistically significant (p = 0.15). The length of stay was longer for patients without FH, 4.45 days compared to 3.93 days (p = 0.38). Multiple logistic regression analysis revealed that type 2 diabetes was not a statistically significant predictor of coronary artery dissection, Table 1.</p></div><div><h3>Conclusions</h3><p>The presence of familial hypercholesterolemia was not a statistically significant predictor of coronary artery dissection, but cardiogenic shock was statistically significant. Further pragmatic clinical trials are needed to evaluate familial hypercholesterolemia and association with complications in patients presenting with acute coronary syndrome.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e534-e535"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141849080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.089
Chris Caraang MD, Halima Tabani BSN
Background/Synopsis
Studies reveal increased incidences of cardiovascular events such as heart attacks and strokes in patients with elevated lipoprotein(a) levels. Niacin-ER has shown to lower lipoprotein(a) levels by approximately 30% though unknown if niacin-ER reduces cardiovascular events in this population. This single center study evaluates 129 patients with a personal or family history of a premature cardiovascular event whose lipoprotein(a) levels were greater than 75nmol/L and prescribed niacin-ER.
Objective/Purpose
Identify patients with personal or family history of premature cardiovascular events through history and screen patients for baseline serum lipoprotein(a); levels greater than or equal to 75nmol/L were included. Patients were monitored for incidences of cardiovascular events, elevation of liver enzymes, and side-effects of niacin-ER.
The study is an effort to determine if niacin-ER can reduce cardiovascular events. While current ASO-RNA and siRNA studies are undergoing trials, niacin-ER may be a less costly alternative.
Methods
The study followed 129 adult patients seen by a Board Certified Lipidologist/Cardiologist from 2014-2024 with baseline lipoprotein(a) greater than 75 nmol/L. Patients were started on 1000 mg-2000 mg (mean 1713 mg) of niacin-ER and a high intensity statin. In the study, 118 patients were prescribed niacin-ER, while 11 were a better fit for PCSK-9 therapy. Of the 118 patients, 36 could not tolerate the flushing, despite mitigating strategies. Patients’ hospital and outpatient records were reviewed for cardiovascular events.
Results
The average baseline value of lipoprotein(a) was 221.59 nmol/L, higher than 35-70 nmol/L in AIM-HIGH and HPS2-THRIVE trials. Current trials with siRNA and ASO-RNA therapies set inclusion criteria at >150 nmol/L. The average lipoprotein(a) after starting niacin-ER amounted to 157.71 nmol/L, a 33.68% reduction.
Fifteen patients laboratory tests resulted in non-prohibitive mildly elevated liver function tests (LFTs), with maximum ALT and AST of 85 U/L and 68 U/L, respectively, after starting niacin.
All patients were on high-intensity statin.
Conclusions
Niacin-ER reduced lipoprotein(a) levels by 33.68%, comparable to published data of 30%.
Niacin-ER continues to be shown as safe and well-tolerated with no incidences of strokes, infections, gastrointestinal symptoms, or rhabdomyolysis; there was a non-significant elevation in LFTs.
In the 83 patients taking niacin-ER, there were no subsequent cardiovascular events up to ten years follow up.
Reduction in cardiovascular events could not be observed with the low sample size. The study reinforces the need to further assess the effectiveness of niacin-ER on cardiovascular events while prospective therapies continue through trials.
{"title":"Association Between Niacin-ER Use, Safety, and Cardiovascular Events. A Single Center Experience.","authors":"Chris Caraang MD, Halima Tabani BSN","doi":"10.1016/j.jacl.2024.04.089","DOIUrl":"10.1016/j.jacl.2024.04.089","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Studies reveal increased incidences of cardiovascular events such as heart attacks and strokes in patients with elevated lipoprotein(a) levels. Niacin-ER has shown to lower lipoprotein(a) levels by approximately 30% though unknown if niacin-ER reduces cardiovascular events in this population. This single center study evaluates 129 patients with a personal or family history of a premature cardiovascular event whose lipoprotein(a) levels were greater than 75nmol/L and prescribed niacin-ER.</p></div><div><h3>Objective/Purpose</h3><p>Identify patients with personal or family history of premature cardiovascular events through history and screen patients for baseline serum lipoprotein(a); levels greater than or equal to 75nmol/L were included. Patients were monitored for incidences of cardiovascular events, elevation of liver enzymes, and side-effects of niacin-ER.</p><p>The study is an effort to determine if niacin-ER can reduce cardiovascular events. While current ASO-RNA and siRNA studies are undergoing trials, niacin-ER may be a less costly alternative.</p></div><div><h3>Methods</h3><p>The study followed 129 adult patients seen by a Board Certified Lipidologist/Cardiologist from 2014-2024 with baseline lipoprotein(a) greater than 75 nmol/L. Patients were started on 1000 mg-2000 mg (mean 1713 mg) of niacin-ER and a high intensity statin. In the study, 118 patients were prescribed niacin-ER, while 11 were a better fit for PCSK-9 therapy. Of the 118 patients, 36 could not tolerate the flushing, despite mitigating strategies. Patients’ hospital and outpatient records were reviewed for cardiovascular events.</p></div><div><h3>Results</h3><p>The average baseline value of lipoprotein(a) was 221.59 nmol/L, higher than 35-70 nmol/L in AIM-HIGH and HPS2-THRIVE trials. Current trials with siRNA and ASO-RNA therapies set inclusion criteria at >150 nmol/L. The average lipoprotein(a) after starting niacin-ER amounted to 157.71 nmol/L, a 33.68% reduction.</p><p>Fifteen patients laboratory tests resulted in non-prohibitive mildly elevated liver function tests (LFTs), with maximum ALT and AST of 85 U/L and 68 U/L, respectively, after starting niacin.</p><p>All patients were on high-intensity statin.</p></div><div><h3>Conclusions</h3><p>Niacin-ER reduced lipoprotein(a) levels by 33.68%, comparable to published data of 30%.</p><p>Niacin-ER continues to be shown as safe and well-tolerated with no incidences of strokes, infections, gastrointestinal symptoms, or rhabdomyolysis; there was a non-significant elevation in LFTs.</p><p>In the 83 patients taking niacin-ER, there were no subsequent cardiovascular events up to ten years follow up.</p><p>Reduction in cardiovascular events could not be observed with the low sample size. The study reinforces the need to further assess the effectiveness of niacin-ER on cardiovascular events while prospective therapies continue through trials.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e554-e555"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.027
Aman Rajpal MD, Yasmin Bains DO
Background/Synopsis
Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder affecting chylomicron metabolism, resulting in severe hypertriglyceridemia (sHTG) associated with recurrent acute pancreatitis (AP). We present a case of young woman with a rare instance of familial lipoprotein lipase (LPL) deficiency during pregnancy.
Objective/Purpose
Despite that FCS is associated with poor quality of life and increased lifelong risk of sHTG and AP, there is lack of awareness about the disease. We aim to describe clinical features and complications associated with FCS, with the overarching objective of enhancing awareness regarding this condition. Additionally, we explore emerging therapies for the treatment of sHTG.
Methods
Literature review and retrospective review of electronic health records were performed.
Results
17-year-old Guatemalan female at 25 weeks gestation presented with acute abdominal pain and was found to have a lipase of 4076 mg/dL, amylase of 860 mg/dL and triglyceride (TG) level of 2233 mg/dL requiring apheresis for sHTG induced AP. She re-presented multiple times with sHTG and required treatment for recurrent AP. Genetic testing showed homozygous LPL gene mutation involving novel early truncation and ABCA1 transporter heterozygosity linked to reduced HDL levels. Patient continues to experience a sequela of complications despite treatment with fibrates, statins, omega-3-acid ethyl esters and a low-fat diet.
Conclusions
There are currently no treatments for FCS except for lifelong fat restrictive diet. Orlistat, a gastric and pancreatic lipase inhibitor has shown some promise in terms of reducing TG levels. Prior therapies have targeted various phenotypes of sHTG in familial combined hyperlipidemia syndromes with off-label use in FCS. More recently, targeted pharmacotherapies for FCS including apoC-III hepatocyte-directed antisense oligonucleotide such as Volanesorsen (approved in Europe) and Olezarsen (currently in phase-3 trial) have shown promise. Preliminary results from the CORE trials have shown significant reduction in TG levels in FCS patients and 100% reduction in AP. Additionally, small interfering ribonucleic acid (siRNA) based therapies are being studied in patients with FCS.
Albeit a rare genetic disorder, FCS should be suspected in patients with sHTG in the absence of secondary causes and should be referred to lipid specialists for further management. FCS in pregnancy can pose even more challenges given increased insulin resistance and fetal and maternal burden of disease. Trials for novel targeted therapies have shown encouraging results and may help reduce ASCVD risk and complications associated with FCS.
{"title":"A Rare Encounter: Familial Lipoprotein Lipase Deficiency in Pregnancy - Case Review and Emerging Therapies for Familial Chylomicronemia Syndrome","authors":"Aman Rajpal MD, Yasmin Bains DO","doi":"10.1016/j.jacl.2024.04.027","DOIUrl":"10.1016/j.jacl.2024.04.027","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive disorder affecting chylomicron metabolism, resulting in severe hypertriglyceridemia (sHTG) associated with recurrent acute pancreatitis (AP). We present a case of young woman with a rare instance of familial lipoprotein lipase (LPL) deficiency during pregnancy.</p></div><div><h3>Objective/Purpose</h3><p>Despite that FCS is associated with poor quality of life and increased lifelong risk of sHTG and AP, there is lack of awareness about the disease. We aim to describe clinical features and complications associated with FCS, with the overarching objective of enhancing awareness regarding this condition. Additionally, we explore emerging therapies for the treatment of sHTG.</p></div><div><h3>Methods</h3><p>Literature review and retrospective review of electronic health records were performed.</p></div><div><h3>Results</h3><p>17-year-old Guatemalan female at 25 weeks gestation presented with acute abdominal pain and was found to have a lipase of 4076 mg/dL, amylase of 860 mg/dL and triglyceride (TG) level of 2233 mg/dL requiring apheresis for sHTG induced AP. She re-presented multiple times with sHTG and required treatment for recurrent AP. Genetic testing showed homozygous LPL gene mutation involving novel early truncation and ABCA1 transporter heterozygosity linked to reduced HDL levels. Patient continues to experience a sequela of complications despite treatment with fibrates, statins, omega-3-acid ethyl esters and a low-fat diet.</p></div><div><h3>Conclusions</h3><p>There are currently no treatments for FCS except for lifelong fat restrictive diet. Orlistat, a gastric and pancreatic lipase inhibitor has shown some promise in terms of reducing TG levels. Prior therapies have targeted various phenotypes of sHTG in familial combined hyperlipidemia syndromes with off-label use in FCS. More recently, targeted pharmacotherapies for FCS including apoC-III hepatocyte-directed antisense oligonucleotide such as Volanesorsen (approved in Europe) and Olezarsen (currently in phase-3 trial) have shown promise. Preliminary results from the CORE trials have shown significant reduction in TG levels in FCS patients and 100% reduction in AP. Additionally, small interfering ribonucleic acid (siRNA) based therapies are being studied in patients with FCS.</p><p>Albeit a rare genetic disorder, FCS should be suspected in patients with sHTG in the absence of secondary causes and should be referred to lipid specialists for further management. FCS in pregnancy can pose even more challenges given increased insulin resistance and fetal and maternal burden of disease. Trials for novel targeted therapies have shown encouraging results and may help reduce ASCVD risk and complications associated with FCS.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Page e502"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.046
Chad Gier MD, Ian Gilchrist MD, Matthew Fordham MD, Nidhi Patel MD, Ella Milchan, Azad Mojahedi MD, Sahana Choudhury NP-C, Andreas Kalogeropoulos MD, John Reilly MD, Luke Riordan MD, Tara Kitz RN, Regina Cohen, Joseph Dougherty PharmD, On Chen MD, Tahmid Rahman MD
<div><h3>Background/Synopsis</h3><p>Dyslipidemia is a leading contributor to atherosclerotic cardiovascular disease (ASCVD). There has been a significant improvement in the treatment of dyslipidemia in the past 10 years with the development of new pharmacotherapies. However adherence to guidelines and patients being prescribed appropriate therapy can be improved.</p></div><div><h3>Objective/Purpose</h3><p>The intent of this review is help enhance clinicians understanding of non-statin lipid lowering therapies in accordance with the 2022 American College of Cardiology Expert Consensus Clinical Decision Pathway (ECDP) on the Role of Non-statin Therapies for LDL-Cholesterol Lowering. We also present a single-center experience implementing a systematic inpatient protocol for lipid lowering therapy (LLT) for secondary prevention of ASCVD.</p></div><div><h3>Methods</h3><p>We review the clinical trials for ezetimibe, evolocumab, alirocumab, inclisiran, bempedoic acid and summarize how the medications are implemented for use in the 2022 American College of Cardiology Expert Consensus Clinical Decision Pathway. We conducted a quality improvement retrospective chart analysis study to assess the proportion of patients admitted with non-ST-elevation myocardial infarction or ST-elevation myocardial infarction who underwent percutaneous coronary intervention and were prescribed LLT at discharge from 1/1/2018 to 08/20/2021. A structured inpatient lipid protocol was implemented with the aim of identifying very-high-risk patients, standardizing the initiation and escalation of LLT, and ensuring appropriate monitoring and follow-up. We identify patients admitted with ASCVD event, and obtain baseline LDL-C level. Our pharmacist reviews the patients in the cardiology units and will make recommendations for next step in management. For patients on statin with an LDL-C above 70mg/dL or not on a statin with an LDL-C above 150mg/dL, we maximize the statin and add a PCSK9 inhibitor on discharge. For patients on statin with an LDL-C below 70mg/dL or not on a statin with an LDL-C below 150mg/dL, we maximize the statin and add either ezetimibe or bempedoic acid. The inpatient case manager determines cost and coverage and communicates with the care management specialist to ensure follow up on authorization for medications. For very high risk patients, a referral is placed in the electronic medical record to our advanced lipid management program and the office calls patient to ensure follow up visit is scheduled with repeat lipid panel checked in 4-12 weeks. Cases are reviewed with the lipidologists, care managers, and nurses during a weekly lipid board to discuss treatment plans for the patients scheduled for the upcoming week.</p></div><div><h3>Results</h3><p>Prior to implementation, review of patients from 1/1/2018 to 08/20/2021, our analysis found that 92% of these patients were prescribed statin therapy, but only 66.2% of them had an LDL-C level below 70 mg/dL at their s
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Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.08.001
P. Barton Duell MD, Kevin C. Maki PhD
{"title":"Disparities in access to pharmacotherapies for weight loss and cardiovascular prevention","authors":"P. Barton Duell MD, Kevin C. Maki PhD","doi":"10.1016/j.jacl.2024.08.001","DOIUrl":"10.1016/j.jacl.2024.08.001","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e485-e487"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.016
Jay Visaria PhD, Eric Stanek PharmD, Jeff White PharmD, Mark Cziraky PharmD, Nilesh Gangan PhD
Background/Synopsis
The 2018 AHA/ACC clinical practice guidelines set standards for treatment selection and low-density lipoprotein cholesterol (LDL-C) lowering among patients with atherosclerotic cardiovascular disease (ASCVD) and/or type 2 diabetes mellitus (T2DM). However, real-world evidence on rates of lipid testing and LDL-C target attainment following guideline directed treatment (GDT) post-release of practice guidelines is limited.
Objective/Purpose
To assess the rates of lipid testing among patients with ASCVD and/or T2DM pre and post initiating statins or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and the extent of LDL-C target attainment in 12 months post-initiation after GDT versus non-GDT post-release of practice guidelines.
Methods
Adults initiating statins or PCSK9i between 01/01/2019 and 12/31/2020 with prior evidence of ASCVD and/or T2DM, and health plan enrollment for 12-month pre- and post-index pharmacy claim date (either statin or PCSK9i) were identified from the Healthcare Integrated Research Database. Lipid testing patterns and LDL-C target attainment rates (<70mg/dL) based on procedure codes or available lab results were examined. GDT was defined as high-intensity statin initiation in patients with ASCVD, moderate- or high-intensity statin initiation in patients with T2DM without ASCVD, PCSK9i in patients with ASCVD added to high-intensity statin and sustained high-intensity statin while persistent on PCSK9i during the 12 months follow-up period. Descriptive statistics were reported, and no statistical testing was performed.
Results
In total, 71,581 statin initiators with ASCVD/T2DM, and 3,038 PCSK9i initiators with ASCVD were included (mean age: 61-65 years; males: 55-60%). Among statin initiators and PCSK9i initiators with prior ASCVD, 72% and 79% had lipid testing during 12-month baseline, and 69% and 75% during 12-month follow-up, respectively. LDL-C target attainment rates during 12-month post-initiation among a subset of patients with at least one valid LDL-C measurement is as follows: 53% in GDT statin initiators with prior ASCVD versus 35% for non-GDT, 35% in GDT statin initiators with prior T2DM without ASCVD versus 16% for non-GDT, 65% among GDT PCSK9i initiators with prior ASCVD versus 53% for non-GDT, and 80% among patients with prior ASCVD with sustained high-intensity statin while persistent on PCSK9i versus 64% for non-persistent PCSK9i/statin.
Conclusions
Lipid testing rates were moderate. LDL-C target attainment in high-risk patients with lipid testing treated per 2018 AHA/ACC guidelines (i.e., GDT) were modestly improved versus non-GDT. Interventions to improve lipid testing rate may increase opportunities for treatment modification based on guidelines and better LDL-C target attainment to help reduce the risk of cardiovascular events.
背景/简介2018 AHA/ACC 临床实践指南为动脉粥样硬化性心血管疾病（ASCVD）和/或 2 型糖尿病（T2DM）患者的治疗选择和降低低密度脂蛋白胆固醇（LDL-C）设定了标准。Objective/Purpose To assess the rates of lipid testing among patients with ASCVD and/or T2DM pre and post initiating statins or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and the extent of LDL-C target attainment in 12 months after initiated after GDT versus non-GDT post released of practice guidelines.目标/目的评估他汀类药物或9型丙脯氨酸转化酶(PCSK9i)抑制剂使用前后ASCVD和/或T2DM患者的血脂检测率，以及使用GDT与未使用GDT后12个月内LDL-C目标的实现程度。方法从医疗保健综合研究数据库中找出2019年1月1日至2020年12月31日期间开始服用他汀类药物或PCSK9i的成人，这些成人之前有证据表明患有ASCVD和/或T2DM，并在12个月前和12个月后的指数药房索赔日期（他汀类药物或PCSK9i）加入了医疗保险。根据程序代码或可用的实验室结果，研究了血脂检测模式和 LDL-C 目标达标率（70 毫克/分升）。GDT的定义是：有ASCVD的患者开始服用高强度他汀类药物；无ASCVD的T2DM患者开始服用中度或高强度他汀类药物；有ASCVD的患者在高强度他汀类药物基础上加用PCSK9i；在12个月的随访期间持续服用高强度他汀类药物，同时持续服用PCSK9i。结果共纳入了 71581 名患有 ASCVD/T2DM 的他汀类药物入选者和 3038 名患有 ASCVD 的 PCSK9i 入选者（平均年龄：61-65 岁；男性：55-60%）。在他汀类药物入选者和曾患 ASCVD 的 PCSK9i 入选者中，分别有 72% 和 79% 的人在 12 个月的基线期间进行了血脂检测，69% 和 75% 的人在 12 个月的随访期间进行了血脂检测。在至少进行过一次有效低密度脂蛋白胆固醇测量的患者子集中，启动后 12 个月的低密度脂蛋白胆固醇目标达标率如下：曾患 ASCVD 的他汀类药物 GDT 启动者的达标率为 53%，而非 GDT 为 35%；曾患 T2DM 但未患 ASCVD 的他汀类药物 GDT 启动者的达标率为 35%，而非 GDT 为 16%；曾患 ASCVD 的他汀类药物 GDT PCSK9i 启动者的达标率为 65%，而非 GDT 为 53%；曾患 ASCVD 并持续服用高强度他汀类药物同时持续服用 PCSK9i 的患者的达标率为 80%，而非持续服用 PCSK9i/ 司他汀的患者的达标率为 64%。根据2018年AHA/ACC指南（即GDT）进行血脂检测的高危患者的LDL-C达标率与非GDT相比略有提高。提高血脂检测率的干预措施可增加根据指南进行治疗调整的机会，并更好地实现低密度脂蛋白胆固醇目标，帮助降低心血管事件风险。
{"title":"Real-World Evaluation of Lipid Testing Rate and Treatment Target Attainment Among High-Risk Patients: Post Release of the 2018 AHA/ACC Practice Guidelines","authors":"Jay Visaria PhD, Eric Stanek PharmD, Jeff White PharmD, Mark Cziraky PharmD, Nilesh Gangan PhD","doi":"10.1016/j.jacl.2024.04.016","DOIUrl":"10.1016/j.jacl.2024.04.016","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>The 2018 AHA/ACC clinical practice guidelines set standards for treatment selection and low-density lipoprotein cholesterol (LDL-C) lowering among patients with atherosclerotic cardiovascular disease (ASCVD) and/or type 2 diabetes mellitus (T2DM). However, real-world evidence on rates of lipid testing and LDL-C target attainment following guideline directed treatment (GDT) post-release of practice guidelines is limited.</p></div><div><h3>Objective/Purpose</h3><p>To assess the rates of lipid testing among patients with ASCVD and/or T2DM pre and post initiating statins or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and the extent of LDL-C target attainment in 12 months post-initiation after GDT versus non-GDT post-release of practice guidelines.</p></div><div><h3>Methods</h3><p>Adults initiating statins or PCSK9i between 01/01/2019 and 12/31/2020 with prior evidence of ASCVD and/or T2DM, and health plan enrollment for 12-month pre- and post-index pharmacy claim date (either statin or PCSK9i) were identified from the Healthcare Integrated Research Database. Lipid testing patterns and LDL-C target attainment rates (<70mg/dL) based on procedure codes or available lab results were examined. GDT was defined as high-intensity statin initiation in patients with ASCVD, moderate- or high-intensity statin initiation in patients with T2DM without ASCVD, PCSK9i in patients with ASCVD added to high-intensity statin and sustained high-intensity statin while persistent on PCSK9i during the 12 months follow-up period. Descriptive statistics were reported, and no statistical testing was performed.</p></div><div><h3>Results</h3><p>In total, 71,581 statin initiators with ASCVD/T2DM, and 3,038 PCSK9i initiators with ASCVD were included (mean age: 61-65 years; males: 55-60%). Among statin initiators and PCSK9i initiators with prior ASCVD, 72% and 79% had lipid testing during 12-month baseline, and 69% and 75% during 12-month follow-up, respectively. LDL-C target attainment rates during 12-month post-initiation among a subset of patients with at least one valid LDL-C measurement is as follows: 53% in GDT statin initiators with prior ASCVD versus 35% for non-GDT, 35% in GDT statin initiators with prior T2DM without ASCVD versus 16% for non-GDT, 65% among GDT PCSK9i initiators with prior ASCVD versus 53% for non-GDT, and 80% among patients with prior ASCVD with sustained high-intensity statin while persistent on PCSK9i versus 64% for non-persistent PCSK9i/statin.</p></div><div><h3>Conclusions</h3><p>Lipid testing rates were moderate. LDL-C target attainment in high-risk patients with lipid testing treated per 2018 AHA/ACC guidelines (<em>i.e.,</em> GDT) were modestly improved versus non-GDT. Interventions to improve lipid testing rate may increase opportunities for treatment modification based on guidelines and better LDL-C target attainment to help reduce the risk of cardiovascular events.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e494-e495"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141838735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.jacl.2024.04.092
Francisco Somoza-Cano MD, Brittany Smith BS, Michael Fatuyi MD, Henry Egbuchiem MD, Nkemputaife Onyechi MD, Joseph Amoah MD
Background/Synopsis
Overweight, in particular, is continuously increasing in the United States of America. In this respect, metabolic syndrome is a strong risk factor for atrial fibrillation.
Objective/Purpose
Our study sought to estimate the clinical outcome of patients admitted for atrial fibrillation with a history of metabolic syndrome.
Methods
Using the National Inpatients Sample Database of 2020, patients admitted with a principal diagnosis of atrial fibrillation with or without metabolic syndrome as a secondary diagnosis were identified. The primary outcome was inpatient mortality with secondary outcomes being the restoration of cardiac rhythm, acute kidney injury (AKI), ablation, post procedure complications, cardiogenic shock, length of hospital stay and charges.
Results
352,160 patients were admitted for atrial fibrillation. Of those, 0.18% had a history of metabolic syndrome. Patient with metabolic syndrome were younger (65 years, 95% C1 63 – 68 VS 71, 95% CI 71 – 71). There was no difference in in-hospital mortality (p=0.1287), ablation (p=0.6724), post procedure complication (p=0.5062), cardiogenic shock (p=0.3777) and acute kidney injury (p=0.9427). We noticed that patient with metabolic syndrome had increased restoration of cardiac rhythm when compared to the general population (p=0.0027). Patient with metabolic syndrome also had increased length of hospital stay (4 days, 95% CI 3.3 – 4.8 VS 3.3, 95% CI 3.3 – 3.4) and hospital charges ($61,006.79, 95% CI 42,662.56 - $79351.02 VS $55394.37 95% CI $ 53470.79 - $57317.95).
Conclusions
The study shows there is no statistically significant difference in inpatient mortality among patients with metabolic syndrome when compared to the general population admitted for atrial fibrillation. Patient with metabolic syndrome had increased restoration of cardiac rhythm, length of hospital stays and charges.
背景/简介在美国，超重现象尤其在持续增加。在这方面，代谢综合征是心房颤动的一个强有力的危险因素。方法利用 2020 年全国住院病人抽样数据库，对主要诊断为心房颤动并伴有或不伴有代谢综合征作为次要诊断的住院病人进行鉴定。主要结果是住院患者死亡率，次要结果是心律恢复、急性肾损伤（AKI）、消融、术后并发症、心源性休克、住院时间和费用。其中，0.18%的患者有代谢综合征病史。患有代谢综合征的患者更年轻（65 岁，95% C1 63 - 68 VS 71 岁，95% CI 71 - 71）。在院内死亡率（P=0.1287）、消融术（P=0.6724）、术后并发症（P=0.5062）、心源性休克（P=0.3777）和急性肾损伤（P=0.9427）方面没有差异。我们注意到，与普通人群相比，代谢综合征患者的心律恢复率较高（p=0.0027）。代谢综合征患者的住院时间（4 天，95% CI 3.3 - 4.8 VS 3.3，95% CI 3.3 - 3.4）和住院费用（61,006.79 美元，95% CI 42,662.56 - 79351.02 VS 55394.37 美元，95% CI 53470.结论该研究显示，与因心房颤动入院的普通人群相比，代谢综合征患者的住院死亡率没有统计学意义上的显著差异。代谢综合征患者的心律恢复时间、住院时间和费用均有所增加。
{"title":"Atrial Fibrillation Outcome in Patients with Metabolic Syndrome.","authors":"Francisco Somoza-Cano MD, Brittany Smith BS, Michael Fatuyi MD, Henry Egbuchiem MD, Nkemputaife Onyechi MD, Joseph Amoah MD","doi":"10.1016/j.jacl.2024.04.092","DOIUrl":"10.1016/j.jacl.2024.04.092","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Overweight, in particular, is continuously increasing in the United States of America. In this respect, metabolic syndrome is a strong risk factor for atrial fibrillation.</p></div><div><h3>Objective/Purpose</h3><p>Our study sought to estimate the clinical outcome of patients admitted for atrial fibrillation with a history of metabolic syndrome.</p></div><div><h3>Methods</h3><p>Using the National Inpatients Sample Database of 2020, patients admitted with a principal diagnosis of atrial fibrillation with or without metabolic syndrome as a secondary diagnosis were identified. The primary outcome was inpatient mortality with secondary outcomes being the restoration of cardiac rhythm, acute kidney injury (AKI), ablation, post procedure complications, cardiogenic shock, length of hospital stay and charges.</p></div><div><h3>Results</h3><p>352,160 patients were admitted for atrial fibrillation. Of those, 0.18% had a history of metabolic syndrome. Patient with metabolic syndrome were younger (65 years, 95% C1 63 – 68 VS 71, 95% CI 71 – 71). There was no difference in in-hospital mortality (p=0.1287), ablation (p=0.6724), post procedure complication (p=0.5062), cardiogenic shock (p=0.3777) and acute kidney injury (p=0.9427). We noticed that patient with metabolic syndrome had increased restoration of cardiac rhythm when compared to the general population (p=0.0027). Patient with metabolic syndrome also had increased length of hospital stay (4 days, 95% CI 3.3 – 4.8 VS 3.3, 95% CI 3.3 – 3.4) and hospital charges ($61,006.79, 95% CI 42,662.56 - $79351.02 VS $55394.37 95% CI $ 53470.79 - $57317.95).</p></div><div><h3>Conclusions</h3><p>The study shows there is no statistically significant difference in inpatient mortality among patients with metabolic syndrome when compared to the general population admitted for atrial fibrillation. Patient with metabolic syndrome had increased restoration of cardiac rhythm, length of hospital stays and charges.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Page e556"},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141844965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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