Repatha (evolocumab) / Dr. Reddy’s, Amgen, Astellas - LARVOL DELTA

Impact of PCSK9 Inhibitors on Carotid Plaques in Patients with Diabetes without Diagnosed ASCVD—A Retrospective Cohort Study (ADA 2025) - "The groups were divided into two groups based on their lipid-lowering regimen: non-PCSK9i group (statins plus non-PCSK9i lipid-lowering medications) or PCSK9i group (statins plus evolocumab 140 mg administered biweekly)... Lipid-lowering regimens that include PCSK9i are more effective in reversing carotid plaque thickness in patients with T2DM without diagnosed ASCVD."

Late-breaking abstract • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Cardiovascular Efficacy of Evolocumab in Persons with Type 1 Diabetes Mellitus—Insights from FOURIER Trial (ADA 2025) - "Available on Friday, June 20, 2025 at 06:30pm CDT."

Clinical • Late-breaking abstract • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Lipid-Lowering Therapy Patterns of High-Risk Cardiovascular Patients without Prior Myocardial Infarction or Stroke—VESALIUS-REAL—Results from Patients with High-Risk Diabetes in the U.S. (ADA 2025) - P3 | "Introduction and Objective: An ongoing clinical trial is investigating the Effect of EVolocumab in PatiEntS at High CArdiovascuLar RIsk WithoUt Prior Myocardial Infarction or Stroke - CardioVascular (VESALIUS-CV; NCT03872401)... The results underscore a substantial gap in testing and treatment in this population, with only a small proportion of patients meeting the American Diabetes Association's recommendation on lipid management to reduce the risk of major ischemic events."

Clinical • Diabetes • Metabolic Disorders

Alirocumab versus Evolocumab on Cardiovascular Outcomes: A Systematic Review and Meta-analysis. (PubMed, Curr Cardiol Rev) - "The use of alirocumab is preferable if the focus is to avoid hospitalizations for unstable angina or stroke, while evolocumab may be an option if one wants to avoid coronary revascularization. Both drugs are effective in reducing cardiovascular outcomes, but alirocumab was superior to evolocumab."

Clinical • Journal • Retrospective data • Cardiovascular • Dyslipidemia • Metabolic Disorders • Myocardial Infarction

Indirect Comparison of the Efficacy and Safety of Alirocumab and Evolocumab on Major Cardiovascular Events: A Systematic Review and Network Meta-analysis (Frontiers) - "This network meta-analysis included 26 RCTs with 64921 patients. Among these, 13 RCTs included patients receiving alirocumab or placebo (n=13365) and 13 RCTs included patients receiving evolocumab or placebo (n=22048). Compared with the placebo, treatment with alirocumab and evolocumab significantly reduced the relative risk of major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction, stroke, and coronary revascularization."

Retrospective data • Cardiovascular

Statins Versus Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors for Primary Cardiovascular Prevention in High-Risk Patients: A Systematic Review. (PubMed, Cureus) - "Although direct evidence of cardiovascular event reduction is still emerging, early indications are favorable, particularly in genetically predisposed populations. Overall, PCSK9 inhibitors appear to be a viable adjunctive option for patients who do not achieve optimal lipid control with statins alone."

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders

NEWTON-CABG: Effect of Evolocumab on Saphenous Vein Graft Patency Following Coronary Artery Bypass Surgery (clinicaltrials.gov) - P4 | N=782 | Active, not recruiting | Sponsor: Unity Health Toronto | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Aug 2025 | Trial primary completion date: Dec 2023 ➔ Jan 2025

Enrollment closed • Trial completion date • Trial primary completion date • Atherosclerosis • Cardiovascular

Impact of GLP-1 Analogs vs. Lipid Lowering Agents on Risk for Acute Pancreatitis in Hypertriglyceridemia: A TriNetX Analysis (ENDO 2025) - "There were 21,106 patients receiving treatment with a GLP-1 analog (Cohort A) and 296,961 patients taking lipid lowering agents which we defined as atorvastatin, rosuvastatin, pravastatin, simvastatin, fenofibrate, ezetimibe, icosapent ethyl, evolocumab (Cohort B). Furthermore, it may reduce mortality for patients who have failed other modalities for weight loss, which is consistent with our findings. Ongoing research is essential to understand the long-term outcomes of GLP-1 analog therapy."

Dyslipidemia • Genetic Disorders • Hypertriglyceridemia • Obesity • Pancreatitis • Severe Hypertriglyceridemia

Breaking the Triglyceride Barrier: A Case of Severe Hypertriglyceridemia Management (ENDO 2025) - "Pharmacologic therapy included continuation of rosuvastatin 40 mg, fenofibrate 160 mg, and ezetimibe 10 mg. Patient was also started on Icosapent ethyl 2 g twice daily and Levothyroxine (LTX) was increased from 125 mcg to 150 mcg due to an elevated TSH level of 10.4 µIU/mL with a free T4 of 1.0 ng/dL...The patient was also prescribed evolocumab, but insurance restrictions required specialist approval...For symptomatic severe HTG cases, particularly with acute pancreatitis, IV insulin and therapeutic plasma exchange are key treatment options. Further research is needed to assess long-term outcomes and the role of emerging therapies in severe HTG management."

Clinical • Cardiovascular • Dyslipidemia • Endocrine Disorders • Hypertension • Hypertriglyceridemia • Obesity • Pancreatitis • Severe Hypertriglyceridemia

Evinacumab as an Effective Treatment Option for Refractory Hypertriglyceridemia (ENDO 2025) - "Despite using atorvastatin 80 mg daily, fenofibrate 162 mg daily, icosapent ethyl 2 g twice daily, and evolocumab 140 mg every 2 weeks, she continued to have hypertriglyceridemia. Evinacumab may be an effective alternative agent for the management of chronic hypertriglyceridemia based on the robust effects seen in our patient. Future research is needed to explore evinacumab's therapeutic targets beyond LDL-C to better modify risk factors for atherosclerosis, as well as CAV progression in heart transplant recipients."

Atherosclerosis • Cardiomyopathy • Cardiovascular • Diabetes • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus • ANGPTL3 • APOB

A Case Series of Heterozygous Familial Hypercholesteremia With PCSK9 Inhibitor Failure (ENDO 2025) - "Evolocumab was switched to alirocumab which initially reduced her LDL-C to 2.65 mmol/L (102.5 mg/dL), but it later rose again. Ezetimibe 10mg daily was added and patient is awaiting approval for inclisiran.CASE 2: An 18-year-old woman with type 1 diabetes and celiac disease was seen in September 2012 for dyslipidemia...Pravastatin 40 mg was started but discontinued due to myalgias...Further research is needed to understand the underlying mechanisms and the likelihood of this occurring in other patients. These cases also highlight the need for ongoing vigilance in patients with high cholesterol and HeFH to ensure optimal cardiovascular protection."

Clinical • Cardiovascular • Celiac Disease • Diabetes • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Immunology • Metabolic Disorders • Musculoskeletal Pain • Pain • Type 1 Diabetes Mellitus

Hypercholesterolemia management in a patient with mitochondrial encephalomyopathy lactic acidosis, and stroke-like episodes (NLA 2025) - "However, one case study in a patient with mitochondrial myopathy due to heteroplasmic mitochondrial DNA missence mutation in MTCO1 gene (m.7671T>A) demonstrated stable CK levels without recurrence of myalgia while taking alirocumab 75 mg every 2 weeks, ezetimibe 10 mg daily, marine omega 3 fatty acids daily, and 145 mg of micronized fenofibrate every 2 days (Cicero et al., 2020)...He had a history of hypercholesterolemia with debilitating myalgias on simvastatin, atorvastatin and rosuvastatin prior to MELAS diagnosis...Ezetimibe 10 mg daily and icosapent ethyl 4 g daily was initiated and well tolerated...Evolocumab 140 mg subcutaneous every 14 days was prescribed and tolerated without side effects...Conclusions This case highlights consideration for MELAS in young adults with stroke-like episodes and demonstrates successful use of non-statin lipid lowering medications to manage hypercholesterolemia. Further research is necessary in this patient population."

Clinical • Cardiovascular • CNS Disorders • Dyslipidemia • Metabolic Disorders • Musculoskeletal Pain • Myositis • Pain

Beyond homozygous familial hypercholesterolemia – emerging therapy for severe familial hypercholesterolemia phenotypes (NLA 2025) - "Methods Case 1: A patient with LDL-C > 400 mg/dL and APOB/PCSK9 VUS showed inadequate response to rosuvastatin, ezetimibe and evolocumab but achieved significant LDL-C reduction after starting evinacumab. As seen in our four cases, double heterozygotes and HoFH phenocopies may present with HoFH-like features and with resistance to standard lipid-lowering therapy. As Rosenson suggests, LDLR receptor independent therapies like evinacumab, may offer hope for improved LDL-C reduction and prevention of atherosclerotic cardiovascular events in refractory hyperlipidemia regardless of genetic profile."

Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB • APOE • LDLR • PCSK9

The PCSK9 paradox: Evolocumab-induced rise in low-density lipoprotein cholesterol in an adult with metastatic uterine cancer on pembrolizumab (NLA 2025) - "Results A 50 year old female with stage IV endometrial adenocarcinoma of the uterus is referred to lipid clinic for management of hyperlipidemia, which has been difficult to control since age 30 and with statin intolerance due to myalgias (trial of atorvastatin and rosuvastatin). We report the second case of a paradoxical response to PCSK9 inhibitor initiation and the first in a cancer patient. Further pathophysiologic explanation for this paradoxical reaction, including the potential for novel immunotherapy agents in mediating such a response, is warranted."

Clinical • IO biomarker • Metastases • Dyslipidemia • Endometrial Adenocarcinoma • Endometrial Cancer • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • Musculoskeletal Pain • Oncology • Pain • Solid Tumor • Uterine Cancer • PCSK9

Effective treatment of statin- and ezetimibe-resistant hyperlipidemia in a patient with active membranous nephrotic syndrome using a PCSK9 inhibitor (NLA 2025) - "Given persistent hyperlipidemia, he was started on the PCSK9 inhibitor Evolocumab. Another case series showed a 36.8% reduction in LDL with PCSK9 inhibitors in 12 patients with refractory MN-, MCD-, or focal segmental glomerulosclerosis (FSGS)-type NS not at LDL goal with statin ± ezetimibe. Our case adds to the existing literature by demonstrating that PCSK9 inhibitors can effectively treat NS-associated hyperlipidemia even before immunotherapy initiation, supporting the need for future studies on PCSK9 inhibitors as a potent therapeutic for NS-associated hyperlipidemia."

Clinical • Addiction (Opioid and Alcohol) • Cardiovascular • Chronic Kidney Disease • Diabetes • Dyslipidemia • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Metabolic Disorders • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Type 1 Diabetes Mellitus

Lipoprotein apheresis to address residual risk in recurrent atherosclerotic events (NLA 2025) - "At this time, icosapent ethyl was added and his lipid profile was controlled with apolipoprotein B of 60 mg/dL...PCSK9 inhibitor was denied again so bempedoic acid was added...Two days after surgery, evolocumab was approved and initiated...For our patient, delays in PCSK9 inhibitor and apheresis initiation likely influenced disease progression. Lipoprotein apheresis has demonstrated a reduction in cardiovascular events."

Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • Peripheral Arterial Disease • Type 2 Diabetes Mellitus • APOB

Comparative cardiovascular outcomes of triple lipid-lowering therapy versus double therapy in patients with atherosclerotic cardiovascular disease: A (NLA 2025) - "While statins and ezetimibe are established therapies, the additional benefit of evolocumab in real-world settings needs further investigation. Conclusions In this large real-world study of ASCVD patients, triple lipid-lowering therapy was associated with significantly lower risks of mortality and major cardiovascular outcomes compared to double therapy. These findings support the consideration of triple therapy in high-risk patients with ASCVD who require additional lipid lowering."

Clinical • Alzheimer's Disease • Atherosclerosis • Atrial Fibrillation • Cardiovascular • CNS Disorders • Congestive Heart Failure • Dementia • Diabetes • Heart Failure • Hypertension • Metabolic Disorders • Myocardial Infarction • Ventricular Tachycardia

Rapid progression of carotid artery stenosis in a postmenopausal patient with untreated familial hypercholesterolemia (NLA 2025) - "The patient was referred to vascular surgery for evaluation and was advised towards medical management with aspirin and lipid-lowering therapy with evolocumab or inclisiran. In particular, ASCVD risk increases following menopause for all women, but is particularly significant in women with FH. Physicians should be aggressive in screening and recommending lipid-lowering therapies for postmenopausal women with FH."

Clinical • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Developmental Disorders • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • Peripheral Arterial Disease

One size doesn't fit all: A dose-dependent twist in PCSK9 monoclonal antibody therapy (NLA 2025) - "The patient experienced myalgias and gastrointestinal side effects to multiple statins, ezetimibe, and bile acid sequestrants. The patient declined bempedoic acid due to concerns about potential side effects...Given the suboptimal response, she was transitioned to alirocumab 150 mg biweekly...It is notable that even with the evolocumab 420 mg monthly formulation, LDL-C lowering was less than what would be expected based on clinical trial data...This case illustrates that some PCSK9 monoclonal antibody “non-responders” may have more robust LDL-C lowering with an alternative dosing formulation. Further research is warranted to better understand the mechanisms and clinical implications of such formulation-dependent responses."

Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Metabolic Disorders • Musculoskeletal Pain • Pain • APOB

The challenges of lipoprotein(a) (NLA 2025) - "The use of Ezetimibe and Niacin were added but despite these interventions, he was unable to achieve an LDL threshold of 70 mg/dL consistently...His LDL level decreased from 80 mg/dL to 17 mg/dL two months after beginning Evolocumab...Conclusions Early detection of Lp(a) allows for early aggressive cardiovascular risk factor modification and for cascade screening of family members given the autosomal dominant inheritance of elevated Lp(a). New therapies that lower Lp(a) up to 90% hold promise for reducing events in these patients."

Atherosclerosis • Cardiovascular • Coronary Artery Disease • Hypertension • Myocardial Infarction • Obstructive Sleep Apnea • Pulmonary Disease • Respiratory Diseases • Sleep Disorder

Evaluating the underutilization of lipid-lowering therapy in Asian patients – A high-risk population (NLA 2025) - "Lipid lowering medications reviewed included rosuvastatin, atorvastatin, lovastatin, pravastatin, ezetimibe, and evolocumab...This is especially notable given the higher risk of ASCVD and its clinical impact in Asian population. We aim to further research into determining the cause of this discrepancy and addressing the gap to improve patient outcomes in this community."

Clinical • Atherosclerosis • Cardiovascular • Heart Failure • Myocardial Infarction

Evaluation of PCSK9 inhibitors in patients with hyperlipidemia (NLA 2025) - "Methods We reviewed all the patients who attended lipid clinic at our tertiary centre between 1st of January 2024 to 30th of June 2024 and who were taking alirocumab or evolocumab alone or with any other lipid-lowering medications. There was no significant difference in age, gender, diagnoses, BMI or statin use between the two groups. Conclusions Our data suggest that a significant proportion of patients on PCSK9 inhibitors failed to achieve target LDL cholesterol and highlights the need for an additional or novel lipid lowering agents in those with significantly elevated baseline LDL cholesterol levels."

Clinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia

Impact of PCSK9 monoclonal antibody inhibitors on Lp(a) reduction in African Americans with elevated Lp(a) (NLA 2025) - "The FOURIER Trial demonstrated that evolocumab reduced Lp(a) by 6.2% to 46.7% with a median reduction of 26.9%...The results of this evaluation showed a greater reduction in median and mean Lp(a) levels compared to prior studies. They also suggest futher evaluation is warranted to determine if there is a real-world racial difference in Lp(a) reduction."

Atherosclerosis • Cardiovascular • Coronary Artery Disease • Ischemic stroke • Myocardial Infarction

Switching to success: Managing hyperlipidemia by switching between PCSK9 inhibitors (NLA 2025) - "Background/Synopsis The first case represents a 54-year-old female with a history of hyperlipidemia, coronary artery disease (coronary calcium score of 4), anxiety, and depression, had previously experienced intolerances to multiple statins, including atorvastatin, simvastatin, and lovastatin, due to muscle aches. She also tried ezetimibe and bempedoic acid, both of which caused significant side effects...In the second patient, after switching from Evolocumab to Alirocumab, the patient tolerated the new therapy without side effects, and her lipid profile is being monitored with a pending lipid panel to confirm efficacy...These findings suggest that PCSK9 inhibitors may offer a viable option for patients with statin intolerance who are not at goal with other therapies, particularly when one PCSK9 inhibitor causes adverse effects but another can be tolerated. This approach underscores the importance of personalized care and close monitoring in managing hyperlipidemia in..."

Cardiovascular • CNS Disorders • Coronary Artery Disease • Depression • Dyslipidemia • Fatigue • Gastroesophageal Reflux Disease • Hypertension • Mood Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Obstructive Sleep Apnea • Orthopedics • Pain • Psychiatry • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Loss of lipid-lowering effect of evolocumab over time: A case report (NLA 2025) - "Objective/Purpose To describe a case of a robust initial response to evolocumab with subsequent loss of lipid-lowering efficacy and evaluate the response to an alternative PCSK9i, alirocumab. Given her initial robust response, a genetic loss-of-function mutation in LDLR or PCSK9 is less likely, raising the possibility of antibody-mediated drug inactivation. Further research is needed to elucidate mechanisms of variable PCSK9i efficacy and determine whether switching to an alternative PCSK9i is an effective strategy."

Case report • Clinical • Coronary Artery Disease • Diabetes • Dyslipidemia • Endocrine Cancer • Endocrine Disorders • Familial Hypercholesterolemia • Genetic Disorders • Glomerulonephritis • Hepatology • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • Type 2 Diabetes Mellitus • APOB • LDLR • PCSK9