Pub Date : 2026-01-01DOI: 10.1016/j.jacl.2025.10.074
Yihang Fan MPH , Lingling Li MS , Wenjun Fan MD, PhD , Jing Gu PhD , Robert J. Sanchez PhD , Nathan D. Wong PhD, MPH, FNLA
BACKGROUND
Patients with elevated low-density lipoprotein-cholesterol (LDL-C) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) and are often undertreated with lipid-lowering therapies (LLT). The impact of electronic health record (EHR) messaging on improving diagnosis and management remains unclear.
OBJECTIVE
We implemented a best practice advisory (BPA) alert for physicians prompted by an LDL-C ≥190 mg/dL in their patients, recommending evaluation for familial hypercholesterolemia (FH) with appropriate guideline-directed treatment.
METHODS
Data on patients with BPAs triggered from August 2021 to June 2024, and with at least 3 months follow-up, were analyzed for changes in diagnoses, medication use, and lipid levels.
RESULTS
Among 665 patients (mean age 58 years, 55% female, 29% Hispanic, and 28% Asian), FH diagnoses (limited to ICD-10 and SNOMED codes) increased from 2.3% to 6%. Statin use rose from 39.4% to 61.7% (P < .0001), with high-intensity statins from 22.9% to 39.0% (P < .0001). LDL-C declined from before to after the BPA alert (adjusted mean change −84.1 mg/dL, P < .0001).
CONCLUSION
BPA alerts for patients with LDL-C ≥ 190 mg/dL improve diagnosis rates for hyperlipidemia and FH, increase LLT use, and reduce LDL-C levels.
{"title":"The impact of electronic health messaging on diagnosis of familial hypercholesterolemia and management of patients with LDL-C ≥190 mg/dL","authors":"Yihang Fan MPH , Lingling Li MS , Wenjun Fan MD, PhD , Jing Gu PhD , Robert J. Sanchez PhD , Nathan D. Wong PhD, MPH, FNLA","doi":"10.1016/j.jacl.2025.10.074","DOIUrl":"10.1016/j.jacl.2025.10.074","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Patients with elevated low-density lipoprotein-cholesterol (LDL-C) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) and are often undertreated with lipid-lowering therapies (LLT). The impact of electronic health record (EHR) messaging on improving diagnosis and management remains unclear.</div></div><div><h3>OBJECTIVE</h3><div>We implemented a best practice advisory (BPA) alert for physicians prompted by an LDL-C ≥190 mg/dL in their patients, recommending evaluation for familial hypercholesterolemia (FH) with appropriate guideline-directed treatment.</div></div><div><h3>METHODS</h3><div>Data on patients with BPAs triggered from August 2021 to June 2024, and with at least 3 months follow-up, were analyzed for changes in diagnoses, medication use, and lipid levels.</div></div><div><h3>RESULTS</h3><div>Among 665 patients (mean age 58 years, 55% female, 29% Hispanic, and 28% Asian), FH diagnoses (limited to ICD-10 and SNOMED codes) increased from 2.3% to 6%. Statin use rose from 39.4% to 61.7% (<em>P</em> < .0001), with high-intensity statins from 22.9% to 39.0% (<em>P</em> < .0001). LDL-C declined from before to after the BPA alert (adjusted mean change −84.1 mg/dL, <em>P</em> < .0001).</div></div><div><h3>CONCLUSION</h3><div>BPA alerts for patients with LDL-C ≥ 190 mg/dL improve diagnosis rates for hyperlipidemia and FH, increase LLT use, and reduce LDL-C levels.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 1","pages":"Pages 204-209"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634033","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 : 2026-01-01DOI: 10.1016/j.jacl.2025.09.028
Pablo González-Bustos MD , Francisco Fuentes-Jiménez MD, PhD , Javier Delgado-Lista MD, PhD , Raquel Ojeda-López MD, PhD , Juan Diego Mediavilla-García MD, PhD
BACKGROUND
Autosomal recessive homozygous familial hypercholesterolemia (AR-HoFH) is a severe lipid disorder leading to early-onset atherosclerotic cardiovascular disease (ASCVD) due to extreme low-density lipoprotein cholesterol (LDL-C) elevations. Despite high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, many patients require LDL-apheresis for LDL-C control.
CASE REPORT
We present the case of a male in his late fifties diagnosed with AR-HoFH, confirmed by genetic testing revealing biallelic pathogenic LDLRAP1 variations (NM_015627.2: c.928_930del/p.Gln310del, homozygous). The patient showed extreme hypercholesterolemia with an LDL-C exceeding 500 mg/dL (12.9 mmol/L) at diagnosis, despite high-intensity statins. At 39 years of age, he suffered a myocardial infarction with multivessel coronary artery disease requiring percutaneous coronary intervention. Despite escalation to rosuvastatin 40 mg daily, ezetimibe 10 mg daily, and alirocumab 150 mg every 2 weeks, LDL-C levels remained persistently elevated. In 2023, recurrent angina prompted coronary angiography, revealing in-stent restenosis in the right coronary artery (RCA) and a new critical stenosis in the left anterior descending (LAD) artery, requiring further revascularization. Given persistently high LDL-C levels averaging 171 mg/dL prior to apheresis despite maximal lipid-lowering therapy, biweekly LDL-apheresis was initiated and continued for 1 year. In December 2024, evinacumab (15 mg/kg intravenous monthly) was introduced following regulatory approval. Over the first 3 months, average LDL-C was reduced to 79.6 mg/dL, representing a 53.5% reduction compared to the mean preapheresis baseline, and permitting discontinuation of apheresis after the final session on January 3, 2025. By March 2025, LDL-C remained stable at 62 mg/dL (1.6 mmol/L), approaching but not fully meeting the <55 mg/dL LDL-C target recommended for secondary prevention according to current European guidelines. The patient tolerated evinacumab well, with comprehensive biochemical monitoring showing no hepatic, renal, or hematologic abnormalities. Although reintroduction of LDL-apheresis remains a potential strategy, lomitapide could also be considered in combination with evinacumab to enhance LDL-C lowering. However, its use in our setting is currently limited by economic constraints.
CONCLUSION
The introduction of evinacumab, an LDL receptor-independent lipid-lowering therapy, achieved robust and sustained LDL-C reduction, while eliminating the need for LDL-apheresis and reducing the indirect logistical burden of frequent hospital-based treatments in this patient with AR-HoFH.
{"title":"Breakthrough LDL-C reduction in a patient with autosomal recessive homozygous familial hypercholesterolemia: Efficacy of evinacumab after LDL-apheresis discontinuation","authors":"Pablo González-Bustos MD , Francisco Fuentes-Jiménez MD, PhD , Javier Delgado-Lista MD, PhD , Raquel Ojeda-López MD, PhD , Juan Diego Mediavilla-García MD, PhD","doi":"10.1016/j.jacl.2025.09.028","DOIUrl":"10.1016/j.jacl.2025.09.028","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Autosomal recessive homozygous familial hypercholesterolemia (AR-HoFH) is a severe lipid disorder leading to early-onset atherosclerotic cardiovascular disease (ASCVD) due to extreme low-density lipoprotein cholesterol (LDL-C) elevations. Despite high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, many patients require LDL-apheresis for LDL-C control.</div></div><div><h3>CASE REPORT</h3><div>We present the case of a male in his late fifties diagnosed with AR-HoFH, confirmed by genetic testing revealing biallelic pathogenic <em>LDLRAP1</em> variations (<em>NM_015627.2: c.928_930del/p.Gln310del</em>, homozygous). The patient showed extreme hypercholesterolemia with an LDL-C exceeding 500 mg/dL (12.9 mmol/L) at diagnosis, despite high-intensity statins. At 39 years of age, he suffered a myocardial infarction with multivessel coronary artery disease requiring percutaneous coronary intervention. Despite escalation to rosuvastatin 40 mg daily, ezetimibe 10 mg daily, and alirocumab 150 mg every 2 weeks, LDL-C levels remained persistently elevated. In 2023, recurrent angina prompted coronary angiography, revealing in-stent restenosis in the right coronary artery (RCA) and a new critical stenosis in the left anterior descending (LAD) artery, requiring further revascularization. Given persistently high LDL-C levels averaging 171 mg/dL prior to apheresis despite maximal lipid-lowering therapy, biweekly LDL-apheresis was initiated and continued for 1 year. In December 2024, evinacumab (15 mg/kg intravenous monthly) was introduced following regulatory approval. Over the first 3 months, average LDL-C was reduced to 79.6 mg/dL, representing a 53.5% reduction compared to the mean preapheresis baseline, and permitting discontinuation of apheresis after the final session on January 3, 2025. By March 2025, LDL-C remained stable at 62 mg/dL (1.6 mmol/L), approaching but not fully meeting the <55 mg/dL LDL-C target recommended for secondary prevention according to current European guidelines. The patient tolerated evinacumab well, with comprehensive biochemical monitoring showing no hepatic, renal, or hematologic abnormalities. Although reintroduction of LDL-apheresis remains a potential strategy, lomitapide could also be considered in combination with evinacumab to enhance LDL-C lowering. However, its use in our setting is currently limited by economic constraints.</div></div><div><h3>CONCLUSION</h3><div>The introduction of evinacumab, an LDL receptor-independent lipid-lowering therapy, achieved robust and sustained LDL-C reduction, while eliminating the need for LDL-apheresis and reducing the indirect logistical burden of frequent hospital-based treatments in this patient with AR-HoFH.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 1","pages":"Pages 210-214"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573809","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 : 2026-01-01DOI: 10.1016/j.jacl.2025.09.020
Junpil Yun MD , Seokhun Yang MD, PhD , Doyeon Hwang MD , Jeehoon Kang MD, PhD , Han-Mo Yang MD, PhD , Kyung Woo Park MD, PhD , Hyun-Jae Kang MD, PhD , Bon-Kwon Koo MD, PhD , Jung-Kyu Han MD, PhD
BACKGROUND
Evidence supports that more aggressive low-density lipoprotein cholesterol (LDL-C) lowering improves outcomes in patients at high cardiovascular risk, but whether one therapeutic strategy is superior to another remains unclear.
OBJECTIVE
This study compared the effectiveness of moderate-intensity statin therapy combined with ezetimibe vs high-intensity statin monotherapy.
METHODS
We conducted a retrospective observational cohort study at a large tertiary university hospital. The study included patients prescribed either moderate-intensity statin with ezetimibe or high-intensity statin between January 1, 2018, and December 31, 2020. Propensity score matching was performed to balance clinical characteristics between the groups. The primary endpoint was an ischemic outcome, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke. Secondary outcomes included cardiovascular death, myocardial infarction, ischemic stroke, revascularization, and all-cause mortality.
RESULTS
Before matching, 1380 patients were prescribed moderate-intensity statin–ezetimibe combination therapy, and 1105 patients were prescribed high-intensity statin therapy. After matching, 971 patients were included in each group. Over a median follow-up of 3.8 years, the primary endpoint occurred in 1.7% of patients in the moderate-intensity statin with ezetimibe group and in 2.1% of patients in the high-intensity statin group. The incidence of major adverse cardiovascular events did not differ significantly between the 2 groups (hazard ratio 0.82, 95% CI: 0.41-1.61, P = .558). No statistically significant differences were observed in secondary outcomes, including cardiovascular death, myocardial infarction, ischemic stroke, revascularization, and all-cause mortality.
CONCLUSION
In this retrospective cohort study, moderate-intensity statin combined with ezetimibe was as effective as high-intensity statin monotherapy in preventing cardiovascular events.
背景：证据支持更积极地降低低密度脂蛋白胆固醇（LDL-C）可改善高危心血管患者的预后，但是否一种治疗策略优于另一种治疗策略尚不清楚。目的：比较中等强度他汀类药物联合依折替米贝与高强度他汀类药物单药治疗的疗效。方法：在某大型三级大学附属医院进行回顾性观察队列研究。该研究纳入了2018年1月1日至2020年12月31日期间服用依折麦布的中等强度他汀类药物或高强度他汀类药物的患者。进行倾向评分匹配以平衡各组之间的临床特征。主要终点是缺血性结局，定义为心血管死亡、非致死性心肌梗死和缺血性卒中的综合结果。次要结局包括心血管死亡、心肌梗死、缺血性卒中、血运重建术和全因死亡率。结果：配对前，1380例患者采用中强度他汀-依泽替米联合治疗，1105例患者采用高强度他汀治疗。配对后，每组971例。在中位3.8年的随访中，依zetimibe中等强度他汀组中1.7%的患者出现了主要终点，而高强度他汀组中2.1%的患者出现了主要终点。两组间主要不良心血管事件的发生率无显著差异（风险比0.82,95% CI: 0.41-1.61, P = 0.558）。在次要结局方面，包括心血管死亡、心肌梗死、缺血性卒中、血运重建术和全因死亡率，未观察到统计学上的显著差异。结论：在这项回顾性队列研究中，在预防心血管事件方面，中等强度他汀类药物联合依折替米比与高强度他汀类药物单药治疗同样有效。
{"title":"Comparative outcomes of moderate-intensity statin with ezetimibe vs high-intensity statin therapy: A retrospective observational cohort study","authors":"Junpil Yun MD , Seokhun Yang MD, PhD , Doyeon Hwang MD , Jeehoon Kang MD, PhD , Han-Mo Yang MD, PhD , Kyung Woo Park MD, PhD , Hyun-Jae Kang MD, PhD , Bon-Kwon Koo MD, PhD , Jung-Kyu Han MD, PhD","doi":"10.1016/j.jacl.2025.09.020","DOIUrl":"10.1016/j.jacl.2025.09.020","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Evidence supports that more aggressive low-density lipoprotein cholesterol (LDL-C) lowering improves outcomes in patients at high cardiovascular risk, but whether one therapeutic strategy is superior to another remains unclear.</div></div><div><h3>OBJECTIVE</h3><div>This study compared the effectiveness of moderate-intensity statin therapy combined with ezetimibe vs high-intensity statin monotherapy.</div></div><div><h3>METHODS</h3><div>We conducted a retrospective observational cohort study at a large tertiary university hospital. The study included patients prescribed either moderate-intensity statin with ezetimibe or high-intensity statin between January 1, 2018, and December 31, 2020. Propensity score matching was performed to balance clinical characteristics between the groups. The primary endpoint was an ischemic outcome, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke. Secondary outcomes included cardiovascular death, myocardial infarction, ischemic stroke, revascularization, and all-cause mortality.</div></div><div><h3>RESULTS</h3><div>Before matching, 1380 patients were prescribed moderate-intensity statin–ezetimibe combination therapy, and 1105 patients were prescribed high-intensity statin therapy. After matching, 971 patients were included in each group. Over a median follow-up of 3.8 years, the primary endpoint occurred in 1.7% of patients in the moderate-intensity statin with ezetimibe group and in 2.1% of patients in the high-intensity statin group. The incidence of major adverse cardiovascular events did not differ significantly between the 2 groups (hazard ratio 0.82, 95% CI: 0.41-1.61, <em>P</em> = .558). No statistically significant differences were observed in secondary outcomes, including cardiovascular death, myocardial infarction, ischemic stroke, revascularization, and all-cause mortality.</div></div><div><h3>CONCLUSION</h3><div>In this retrospective cohort study, moderate-intensity statin combined with ezetimibe was as effective as high-intensity statin monotherapy in preventing cardiovascular events.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 1","pages":"Pages 87-95"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145504670","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 : 2026-01-01DOI: 10.1016/j.jacl.2025.10.072
Venu Menon MD , LeAnne Bloedon MS , Na Li PhD , A. Michael Lincoff MD , Stephen J. Nicholls MBBS, PhD , Heather A. Powell PharmD , Steven E. Nissen MD
BACKGROUND
Bempedoic acid is a prodrug that reduces circulating low-density lipoprotein (LDL) cholesterol levels by inhibiting the liver enzyme adenosine triphosphate-citrate lyase. Treatment of statin intolerant patients with bempedoic acid was associated with a significantly reduced risk of the primary composite endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) in the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes Trial.
OBJECTIVE
To evaluate impact of additional lipid modifying therapy (LMT) on the primary composite endpoint of the CLEAR Outcomes Trial.
RESULTS
Utilization of adjunctive LMT was observed in 1749 (12.5%) enrolled patients. The most common adjunctive LMTs reported were statins (4.0% vs 6.5%), ezetimibe (2.7% vs 5.5%), and proprotein convertase subtilisin/kexin type 9 inhibitors (2.8% vs 4.4%) in the bempedoic acid and placebo groups, respectively. The majority of first MACE-4 events (92.9% of events in bempedoic acid and 90.9% of events in placebo) preceded the initiation of adjunctive LMT. When censored at the time of initiating adjunctive LMT, primary event reduction was observed in favor of bempedoic acid compared to placebo (hazard ratio [HR]: 0.86 [95% CI, 0.77-0.94]) which was similar to the reduction noted with bempedoic acid in the overall trial (HR of 0.87 [95% CI, 0.79-0.96], P = .004).
CONCLUSIONS
The utilization of additional LMT following randomization had no impact on the observed results of the CLEAR Outcomes trial.
{"title":"Lack of impact of adjunctive lipid-modifying therapy in the CLEAR Outcomes trial","authors":"Venu Menon MD , LeAnne Bloedon MS , Na Li PhD , A. Michael Lincoff MD , Stephen J. Nicholls MBBS, PhD , Heather A. Powell PharmD , Steven E. Nissen MD","doi":"10.1016/j.jacl.2025.10.072","DOIUrl":"10.1016/j.jacl.2025.10.072","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Bempedoic acid is a prodrug that reduces circulating low-density lipoprotein (LDL) cholesterol levels by inhibiting the liver enzyme adenosine triphosphate-citrate lyase. Treatment of statin intolerant patients with bempedoic acid was associated with a significantly reduced risk of the primary composite endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) in the CLEAR (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) Outcomes Trial.</div></div><div><h3>OBJECTIVE</h3><div>To evaluate impact of additional lipid modifying therapy (LMT) on the primary composite endpoint of the CLEAR Outcomes Trial.</div></div><div><h3>RESULTS</h3><div>Utilization of adjunctive LMT was observed in 1749 (12.5%) enrolled patients. The most common adjunctive LMTs reported were statins (4.0% vs 6.5%), ezetimibe (2.7% vs 5.5%), and proprotein convertase subtilisin/kexin type 9 inhibitors (2.8% vs 4.4%) in the bempedoic acid and placebo groups, respectively. The majority of first MACE-4 events (92.9% of events in bempedoic acid and 90.9% of events in placebo) preceded the initiation of adjunctive LMT. When censored at the time of initiating adjunctive LMT, primary event reduction was observed in favor of bempedoic acid compared to placebo (hazard ratio [HR]: 0.86 [95% CI, 0.77-0.94]) which was similar to the reduction noted with bempedoic acid in the overall trial (HR of 0.87 [95% CI, 0.79-0.96], <em>P</em> = .004).</div></div><div><h3>CONCLUSIONS</h3><div>The utilization of additional LMT following randomization had no impact on the observed results of the CLEAR Outcomes trial.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 1","pages":"Pages 196-199"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756793","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 : 2026-01-01DOI: 10.1016/j.jacl.2025.11.013
Bruce A. Warden PharmD , Paul Barton Duell MD , John D. Bucheit PharmD , Jonathan Q. Purnell MD
BACKGROUND
Obesity is a chronic disease, rooted in genetic predisposition and homoeostatic counter-regulatory adaptive and hormonal responses, with escalating prevalence rates and numerous associated health consequences.
SOURCES OF MATERIAL
Historically, interventions beyond lifestyle for the treatment of obesity have been underutilized, stigmatized, and held to different standards of validation compared to treatments for other chronic cardiovascular risk factors.
ABSTRACT OF FINDINGS
Contemporary management of obesity requires implementation of lifestyle modifications, employment of pharmacotherapy, and in more severe cases, surgical intervention. The purpose of this manuscript is to review obesity medication (OM) use in adults, with an emphasis on glucagon-like peptide-1 receptor agonists (GLP-1 RA) and GLP-1 RA/glucose- dependent insulinotropic polypeptide (GIP) dual receptor agonists, focusing on patient selection, strategies for initiation and titration of these medications in clinical practice, emerging evidence of benefit and potential risk, as well as medication access and cost considerations.
CONCLUSION
GLP-1 RAs have emerged as a highly effective, safe, and well tolerated pharmacotherapy option for the management of obesity, possessing a myriad disease-modifying outcomes and capable of curtailing the rapid rise in obesity and related complications.
{"title":"Pharmacotherapy for obesity management—Emphasizing the role of GLP-1 receptor agonist-based therapeutics","authors":"Bruce A. Warden PharmD , Paul Barton Duell MD , John D. Bucheit PharmD , Jonathan Q. Purnell MD","doi":"10.1016/j.jacl.2025.11.013","DOIUrl":"10.1016/j.jacl.2025.11.013","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Obesity is a chronic disease, rooted in genetic predisposition and homoeostatic counter-regulatory adaptive and hormonal responses, with escalating prevalence rates and numerous associated health consequences.</div></div><div><h3>SOURCES OF MATERIAL</h3><div>Historically, interventions beyond lifestyle for the treatment of obesity have been underutilized, stigmatized, and held to different standards of validation compared to treatments for other chronic cardiovascular risk factors.</div></div><div><h3>ABSTRACT OF FINDINGS</h3><div>Contemporary management of obesity requires implementation of lifestyle modifications, employment of pharmacotherapy, and in more severe cases, surgical intervention. The purpose of this manuscript is to review obesity medication (OM) use in adults, with an emphasis on glucagon-like peptide-1 receptor agonists (GLP-1 RA) and GLP-1 RA/glucose- dependent insulinotropic polypeptide (GIP) dual receptor agonists, focusing on patient selection, strategies for initiation and titration of these medications in clinical practice, emerging evidence of benefit and potential risk, as well as medication access and cost considerations.</div></div><div><h3>CONCLUSION</h3><div>GLP-1 RAs have emerged as a highly effective, safe, and well tolerated pharmacotherapy option for the management of obesity, possessing a myriad disease-modifying outcomes and capable of curtailing the rapid rise in obesity and related complications.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 1","pages":"Pages 65-96"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146196890","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 : 2026-01-01DOI: 10.1016/j.jacl.2025.10.065
Bruce A. Warden PharmD, BCPS, CLS, FNLA, FASPC , Paul Barton Duell MD, MNLA, FAHA
OBJECTIVE
Evaluate efficacy and tolerability of bempedoic acid in homozygous familial hyper cholesterolemia (HoFH).
METHODS
A single-center retrospective study of HoFH patients prescribed bempedoic acid between February 2020 and May 2025. Patients were managed according to our clinical standard of care, with routine assessments of lipids, medication tolerability, and adherence. The primary endpoint was percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to first follow-up. Secondary endpoints evaluated LDL-C changes at other timepoints, LDL-C goal attainment, medication access, and tolerability.
RESULTS
Of the 14 HoFH patients treated within our clinic, 5 (mean age 41.4 years, 60% female) were initiated on bempedoic acid, and 4 continued treatment. Pre-existing atherosclerotic cardiovascular disease (ASCVD) was present in 4 of 5 patients, and baseline mean ± SD LDL-C was 131 ± 62.4 mg/dL. Patients were managed on a mean of 3.8 lipid-lowering therapies at baseline, all with statins (60% high-intensity). Bempedoic acid reduced LDL-C by a mean ± SD of –33.2% ± 15.1% to an on-treatment LDL-C of 71 ± 30.9 mg/dL at first follow-up (median 2.9 months). LDL-C reduction of –29.4% ± 13.1% to an on-treatment LDL-C of 75 ± 29.6 mg/dL was seen at most recent follow-up (median 25.6 months). Two patients achieved recommended LDL-C goals on bempedoic acid. The medication was well tolerated, with 60% free from adverse events.
CONCLUSION
Bempedoic acid in patients with HoFH was both effective for LDL-C lowering and tolerable in this cohort of patients. This represents a novel treatment approach in a very high-risk patient population requiring multi-drug regimen for lipid optimization and cardiovascular protection.
{"title":"Real-world evaluation of bempedoic acid use in patients with homozygous familial hypercholesterolemia","authors":"Bruce A. Warden PharmD, BCPS, CLS, FNLA, FASPC , Paul Barton Duell MD, MNLA, FAHA","doi":"10.1016/j.jacl.2025.10.065","DOIUrl":"10.1016/j.jacl.2025.10.065","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Evaluate efficacy and tolerability of bempedoic acid in homozygous familial hyper cholesterolemia (HoFH).</div></div><div><h3>METHODS</h3><div>A single-center retrospective study of HoFH patients prescribed bempedoic acid between February 2020 and May 2025. Patients were managed according to our clinical standard of care, with routine assessments of lipids, medication tolerability, and adherence. The primary endpoint was percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to first follow-up. Secondary endpoints evaluated LDL-C changes at other timepoints, LDL-C goal attainment, medication access, and tolerability.</div></div><div><h3>RESULTS</h3><div>Of the 14 HoFH patients treated within our clinic, 5 (mean age 41.4 years, 60% female) were initiated on bempedoic acid, and 4 continued treatment. Pre-existing atherosclerotic cardiovascular disease (ASCVD) was present in 4 of 5 patients, and baseline mean ± SD LDL-C was 131 ± 62.4 mg/dL. Patients were managed on a mean of 3.8 lipid-lowering therapies at baseline, all with statins (60% high-intensity). Bempedoic acid reduced LDL-C by a mean ± SD of –33.2% ± 15.1% to an on-treatment LDL-C of 71 ± 30.9 mg/dL at first follow-up (median 2.9 months). LDL-C reduction of –29.4% ± 13.1% to an on-treatment LDL-C of 75 ± 29.6 mg/dL was seen at most recent follow-up (median 25.6 months). Two patients achieved recommended LDL-C goals on bempedoic acid. The medication was well tolerated, with 60% free from adverse events.</div></div><div><h3>CONCLUSION</h3><div>Bempedoic acid in patients with HoFH was both effective for LDL-C lowering and tolerable in this cohort of patients. This represents a novel treatment approach in a very high-risk patient population requiring multi-drug regimen for lipid optimization and cardiovascular protection.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 1","pages":"Pages 96-103"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582004","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}
Atherosclerotic cardiovascular disease remains a predominant cause of morbidity and mortality worldwide, driven by complex interactions between lipid metabolism and chronic inflammation. While evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, is established in lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, its long-term effects on inflammatory biomarkers—and potential sex-specific responses—are not fully understood.
OBJECTIVE
This study aimed to elucidate the impact of prolonged evolocumab therapy on inflammation markers in a routine clinical setting, focusing on sex-related differences.
METHODS
We analyzed data from 202 hypercholesterolemic patients (111 men, 91 women) treated with evolocumab for at least 36 months. Key inflammatory indices, including the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and platelet-to-monocyte ratio (PMR), were assessed longitudinally alongside traditional lipid parameters.
RESULTS
Significant sex-related differences emerged in inflammatory profiles: men exhibited consistently higher MHR levels at baseline (P = .010) and throughout follow-up (P < .001), whereas women showed persistently elevated PMR values (P < .001). Intriguingly, a strong inverse correlation was observed between lymphocyte count and lipoprotein(a) levels in women (rs = −0.885, P < .001), a pattern absent in men, suggesting distinct immunometabolic mechanisms.
CONCLUSION
Our findings reveal pronounced biological sex differences in inflammatory responses to long-term evolocumab therapy, highlighting the need to incorporate sex-specific considerations in cardiovascular risk management and treatment monitoring. These novel insights pave the way for personalized therapeutic strategies and call for further investigation into the clinical significance of inflammation in lipid-lowering treatment outcomes.
{"title":"Sex differences in inflammatory biomarkers during long-term evolocumab therapy","authors":"Federica Fogacci MDc , Serra İlayda Yerlitaş Taştan MStat, PhD , Marina Giovannini BD , Egidio Imbalzano MD, PhD , Dmitri Mitselman MD , Claudio Borghi MD , Gökmen Zararsız MStat, PhD , Arrigo F.G. Cicero MD, PhD","doi":"10.1016/j.jacl.2025.11.011","DOIUrl":"10.1016/j.jacl.2025.11.011","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Atherosclerotic cardiovascular disease remains a predominant cause of morbidity and mortality worldwide, driven by complex interactions between lipid metabolism and chronic inflammation. While evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, is established in lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, its long-term effects on inflammatory biomarkers—and potential sex-specific responses—are not fully understood.</div></div><div><h3>OBJECTIVE</h3><div>This study aimed to elucidate the impact of prolonged evolocumab therapy on inflammation markers in a routine clinical setting, focusing on sex-related differences.</div></div><div><h3>METHODS</h3><div>We analyzed data from 202 hypercholesterolemic patients (111 men, 91 women) treated with evolocumab for at least 36 months. Key inflammatory indices, including the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and platelet-to-monocyte ratio (PMR), were assessed longitudinally alongside traditional lipid parameters.</div></div><div><h3>RESULTS</h3><div>Significant sex-related differences emerged in inflammatory profiles: men exhibited consistently higher MHR levels at baseline (<em>P</em> = .010) and throughout follow-up (<em>P</em> < .001), whereas women showed persistently elevated PMR values (<em>P</em> < .001). Intriguingly, a strong inverse correlation was observed between lymphocyte count and lipoprotein(a) levels in women (<em>r<sub>s</sub></em> = −0.885, <em>P</em> < .001), a pattern absent in men, suggesting distinct immunometabolic mechanisms.</div></div><div><h3>CONCLUSION</h3><div>Our findings reveal pronounced biological sex differences in inflammatory responses to long-term evolocumab therapy, highlighting the need to incorporate sex-specific considerations in cardiovascular risk management and treatment monitoring. These novel insights pave the way for personalized therapeutic strategies and call for further investigation into the clinical significance of inflammation in lipid-lowering treatment outcomes.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"20 1","pages":"Pages 75-86"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723206","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}
Background: National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments.
Objective: We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events.
Results: Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS).
Conclusion: Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+.
背景：需要国家流行病学数据来为国家特定的预防保健政策和新开发的治疗方法提供信息。目的：我们旨在分析希腊临床相关特殊人群的流行病学数据，以进行靶向治疗，并评估脂蛋白(a) [Lp(a)]作为风险增强因子的效用。方法：本分析纳入两个独立队列：(1)连续招募三级门诊脂质诊所评估的患者（雅典血管代谢队列[AAC]， n = 1106），具有可用的外周血管标志物；(2)希腊普通人群样本（ATTICA研究[AS]， n = 2682），具有可用的20年动脉粥样硬化性心血管疾病（ASCVD）事件随访数据。结果：8.3%的AS（≥50 mg/dL）和18.9%的AAC（≥125 nmol/L）患者Lp(a)升高（无ASCVD为16.0%，ASCVD为22.1%,P = 0.006）。Lp(a)水平升高与颈动脉、冠状动脉和下肢动脉粥样硬化增加相关(P结论：在8.3%的普通人群队列中观察到Lp(a)水平升高，在脂质临床队列中观察到高达23.9%的ASCVD患者中观察到Lp(a)水平升高，突出了ASCVD类别之间的风险梯度。将Lp(a)作为风险增强因子，在已验证的HellenicSCOREII+基础上改进了ASCVD风险重新分类。
{"title":"Country-specific prevalence and clinical relevance of elevated Lp(a) as a risk enhancer in 2 Greek cohorts.","authors":"Dimitrios Delialis, Polyxeni Manifava, Sofia-Panagiota Giannakopoulou, Christina Konstantaki, Stavros Athanasopoulos, Georgios Zervas, Panagiotis Nastatos, Georgios Mavraganis, Kateryna Sopova, Maria-Angeliki Dimopoulou, Lydia Kokkinidou, Yannis Skoumas, Christos Pitsavos, Nikolaos Rachiotis, Lasthenis Angelidakis, Dimitrios Papoutsis, Peggy Kostakou, Elisabeth Samouilidou, Achilleas A Zacharoulis, Konstantinos Stellos, Evangellos Liberopoulos, Christina Chrysochoou, Georgios Georgiopoulos, Demosthenes Panagiotakos, Kimon Stamatelopoulos","doi":"10.1016/j.jacl.2025.12.016","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.12.016","url":null,"abstract":"<p><strong>Background: </strong>National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments.</p><p><strong>Objective: </strong>We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events.</p><p><strong>Results: </strong>Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS).</p><p><strong>Conclusion: </strong>Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018611","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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