Treatment of Hypertriglyceridemia: A Review of Therapies in the Pipeline

2021 ◽  
pp. 089719002110534
Author(s):  
Jiashan Xu ◽  
Emily Ashjian
Keyword(s):  
Risk Reduction ◽  
Heart Association ◽  
Mesh Term ◽  
Secondary Outcome ◽  
Atherosclerotic Cardiovascular Disease ◽  
Omega 3 ◽  
Individual Agent ◽  
Icosapent Ethyl ◽  
Severe Hypertriglyceridemia ◽  
Ascvd Risk

Background The 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines and 2021 ACC Expert Consensus Decision Pathway recommend nonpharmacological interventions and initiation of statin therapy for patients with moderate hypertriglyceridemia and addition of fibrates or omega-3 fatty acids in severe hypertriglyceridemia. Although the association between triglyceride (TG) lowering and atherosclerotic cardiovascular disease (ASCVD) risk reduction remains controversial, patients with hypertriglyceridemia may represent a subgroup that require additional therapy to further reduce residual ASCVD risk. Moreover, medications that target novel pathways could provide alternative options for patients who are intolerant of existing therapies or doses needed to provide adequate triglyceride lowering. Objective: Assess recent evidence for TG-lowering agents including omega-3 fatty acid-based therapies, PPARα modulators, apoC-III mRNA antisense inhibitors, angiopoietin-like 3 (ANGPTL3) antibodies, and herbal supplements. Methods: A literature search was performed using PubMed with hypertriglyceridemia specified as a MeSH term or included in the title or abstract of the article along with each individual agent. For inclusion, trials needed to have a primary or secondary outcome of TG levels or TG lowering. Conclusion: Currently, the only US Food and Drug Administration approved medication for CV risk reduction in patients with hypertriglyceridemia is icosapent ethyl. Results from phase 3 trials for CaPre, pemafibrate, and volanesorsen as well as additional evidence for pipeline pharmacotherapies with novel mechanisms of action (e.g., ApoC-III mRNA antisense inhibitors and ANGPTL3 antibodies) will help to guide future pharmacotherapy considerations for patients with hypertriglyceridemia.

Patients Living With HIV Are Less Likely to Receive Appropriate Statin Therapy for Cardiovascular Disease Risk Reduction

2021 ◽  
pp. 089719002199979
Author(s):  
Roshni P. Emmons ◽  
Nicholas V. Hastain ◽  
Todd A. Miano ◽  
Jason J. Schafer
Keyword(s):  
Cardiovascular Disease ◽  
Logistic Regression ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Blood Cholesterol ◽  
Control Group ◽  
Atherosclerotic Cardiovascular Disease ◽  
Ascvd Risk ◽  
Living With Hiv ◽  
To Receive

Background: Recent studies suggest that statins are underprescribed in patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD), but none have assessed if eligible patients receive the correct statin and intensity compared to uninfected controls. Objectives: The primary objective was to determine whether statin-eligible PLWH are less likely to receive appropriate statin therapy compared to patients without HIV. Methods: This retrospective study evaluated statin eligibility and prescribing among patients in both an HIV and internal medicine clinic at an urban, academic medical center from June-September 2018 using the American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk. Patients were assessed for eligibility and actual treatment with appropriate statin therapy. Characteristics of patients appropriately and not appropriately treated were compared with chi-square testing and predictors for receiving appropriate statin therapy were determined with logistic regression. Results: A total of 221/300 study subjects were statin-eligible. Fewer statin-eligible PLWH were receiving the correct statin intensity for their risk benefit group versus the uninfected control group (30.2% vs 67.0%, p < 0.001). In the multivariable logistic regression analysis, PLWH were significantly less likely to receive appropriate statin therapy, while those with polypharmacy were more likely to receive appropriate statin therapy. Conclusion: Our study reveals that PLWH may be at a disadvantage in receiving appropriate statin therapy for ASCVD risk reduction. This is important given the heightened risk for ASCVD in this population, and strategies that address this gap in care should be explored.

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE ALGORITHM – 2020 EXECUTIVE SUMMARY

2020 ◽  
Vol 26 (10) ◽  
pp. 1196-1224 ◽  
Author(s):  
Yehuda Handelsman ◽  
Paul S. Jellinger ◽  
Chris K. Guerin ◽  
Zachary T. Bloomgarden ◽  
Eliot A. Brinton ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Icosapent Ethyl ◽  
Lipid Disorders ◽  
Ascvd Risk

The treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids. Secondary causes of lipid disorders should be addressed, and pharmacologic therapy initiated based on a patient’s risk for atherosclerotic cardiovascular disease (ASCVD). Patients at extreme ASCVD risk should be treated with high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol (LDL-C) of <55 mg/dL, and those at very high ASCVD risk should be treated to achieve LDL-C <70 mg/dL. Treatment for moderate and high ASCVD risk patients may begin with a moderate-intensity statin to achieve an LDL-C <100 mg/dL, while the LDL-C goal is <130 mg/dL for those at low risk. In all cases, treatment should be intensified, including the addition of other LDL-C-lowering agents (i.e., proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, colesevelam, or bempedoic acid) as needed to achieve treatment goals. When targeting triglyceride levels, the desirable goal is <150 mg/dL. Statin therapy should be combined with a fibrate, prescription-grade omega-3 fatty acid, and/or niacin to reduce triglycerides in all patients with triglycerides ≥500 mg/dL, and icosapent ethyl should be added to a statin in any patient with established ASCVD or diabetes with ≥2 ASCVD risk factors and triglycerides between 135 and 499 mg/dL to prevent ASCVD events. Management of additional risk factors such as elevated lipoprotein(a) and statin intolerance is also described. Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; ACS = acute coronary syndrome; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BA = bempedoic acid; CAC = coronary artery calcium; CHD = coronary heart disease; CK = creatine kinase; CKD = chronic kidney disease; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FCS = familial chylomicronemia syndrome; FDA = United States Food and Drug Administration; FOURIER = Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; HDL-C = high-density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hyper-cholesterolemia; hsCRP = high-sensitivity C reactive protein; IDL = intermediate-density lipoproteins; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; IPE = icosapent ethyl; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein a; MACE = major adverse cardiovascular events; MI = myocardial infarction; OSA = obstructive sleep apnea; PCSK9 = proprotein convertase subtilisin/kexin type 9; REDUCE-IT = Reduction of Cardiovascular Events with EPA-Intervention Trial; UKPDS = United Kingdom Prospective Diabetes Study; U.S. = United States; VLDL = very-low-density lipoproteins

scholarly journals Potential Benefits of Icosapent Ethyl on the Lipid Profile: Case Studies

2014 ◽  
Vol 8 ◽  
pp. CMC.S13571 ◽  
Author(s):  
Daniel E. Hilleman ◽  
Mark A. Malesker
Keyword(s):  
Fatty Acids ◽  
Case Reports ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Heart Association ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Icosapent Ethyl ◽  
Epa And Dha ◽  
Potential Benefits

The cardiovascular benefits of marine-derived omega-3 fatty acids are supported by epidemiologic and clinical studies. Both healthy patients and those with confirmed coronary heart disease are advised by the American Heart Association to consume omega-3 fatty acids either through dietary fatty fish or fish oil products. We present two case reports of patients with dyslipidemia who were switched from an omega-3 dietary supplement or a prescription omega-3 drug containing eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) to a new prescription EPA-only drug, icosapent ethyl (IPE). Products containing a combination of EPA and DHA, including dietary supplements and prescription products, are more likely to increase low-density lipoprotein cholesterol (LDL-C) levels compared with pure EPA-only products. The lipid profiles of these two patients were improved with IPE treatment, illustrating the potentially favorable effects of IPE compared with other products containing both EPA and DHA.

scholarly journals 338. Patients Living with HIV Infection Are Less Likely to Receive the Correct Intensity of Statin Therapy for Cardiovascular Disease Risk Reduction

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S179-S180
Author(s):  
Jason J Schafer ◽  
Roshni Patel ◽  
Nicholas V Hastain ◽  
Todd Miano
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Univariate Analysis ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Panel ◽  
Ascvd Risk ◽  
Living With Hiv ◽  
To Receive

Abstract Background Patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD) should receive risk reduction interventions recommended in current guidelines. This includes routine ASCVD risk assessments and when eligible, statins selected and dosed to achieve appropriate low-density lipoprotein cholesterol (LDL-C) reduction. Recent studies suggest that statins are underprescribed in PLWH, but none have assessed if eligible patients receive the correct statin intensity compared with uninfected controls. Methods This retrospective study evaluated statin eligibility and prescribing among consecutive patients in an HIV clinic and an internal medicine clinic at an urban, academic medical center from June-September 2018. To determine statin eligibility, the 2013 American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk was used. Patients aged 40–75 that had a lipid panel obtained within the last year were included. All patients were assessed to determine eligibility for and actual treatment with appropriate statin therapy. Characteristics of patients correctly and incorrectly treated with statins were compared with chi-square testing and predictors for receiving correct statin therapy were determined with logistic multivariable regression. Results A total of 221/300 study subjects were statin eligible (Table 1). While many eligible PLWH were receiving a statin (54/106), considerably fewer were on the correct statin intensity for their benefit group (33/106). In the univariate analysis (Table 2), correctly treated patients were less likely to be PLWH or female, and were more likely to have polypharmacy and hypertension. In the multivariable logistic regression analysis (Table 3), PLWH (OR 0.26, CI95 0.12–0.57)) were significantly less likely to receive correct statin therapy, while those with concomitant polypharmacy were significantly more likely to receive correct statin therapy (OR 5.52, CI95 1.94, 15.69). Conclusion This study reveals that PLWH may be at a substantial disadvantage in terms of receiving correct statin therapy for ASCVD risk reduction. This finding may be particularly important given the heightened risk for ASCVD in this patient population. Disclosures All authors: No reported disclosures.

Current Controversies With Recent Cholesterol Treatment Guidelines

2015 ◽  
Vol 29 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Elizabeth Phillips ◽  
Joseph J. Saseen
Keyword(s):  
Treatment Guidelines ◽  
Traditional Approach ◽  
Heart Association ◽  
Patient Specific ◽  
Atherosclerotic Cardiovascular Disease ◽  
Paradigm Change ◽  
Cholesterol Treatment ◽  
Risk Patients ◽  
Ascvd Risk

Several guidelines and expert recommendations have been published recently regarding the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) risk. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a drastic paradigm change in the treatment of cholesterol where treatment, based on level of cardiovascular risk, is based around using a fixed statin intensity therapy. This approach is endorsed by the American Diabetes Association. However, recommendations by the National Lipid Association (NLA) consist of the traditional approach of titrating therapy to achieve patient-specific lipoprotein targets. Despite the differences in overall approaches, the use of statin therapy as the cornerstone of treatment to reduce risk of cardiovascular events in at risk patients is a strong common theme. Clinicians should be aware of these differences, as they represent controversies with the overall treatment of ASCVD risk. Additional controversies related to the treatment of patients with ASCVD risk pertain to the role of nonstatin drugs and approaches to managing side effects. These topics are reviewed within this article and discuss implications for patient care.

scholarly journals 941. Incarcerated patients living with HIV: Atherosclerotic cardiovascular disease risk and management

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S503-S504
Author(s):  
Sarah M Michienzi ◽  
Thomas D Chiampas ◽  
Amy Valkovec ◽  
Siria Arzuaga ◽  
Mahesh C Patel ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Heart Association ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Panel ◽  
Ascvd Risk ◽  
Living With Hiv

Abstract Background The 2018 American Heart Association and American College of Cardiology (AHA/ACC) 2018 Guideline on the Management of Blood Cholesterol included human immunodeficiency virus (HIV) as an atherosclerotic cardiovascular disease (ASCVD) risk enhancer for the first time. Our study investigates if patients living with HIV in the Illinois Department of Corrections (IDOC) were prescribed appropriate HMG-CoA reductase inhibitor (statin) therapy following release of these guidelines based on risk. Methods This was a retrospective study of patients with &gt; 1 visit in our multidisciplinary HIV IDOC Telemedicine Clinic from 1/1/19-6/1/19. Our prescriptive authority is limited to HIV and directly related conditions, and we provide recommendations to on-site providers for other comorbidities. Included patients were &gt; 18 years of age, HIV positive, and incarcerated within IDOC. Excluded patients had existing ASCVD. Data from the first visit in the study period were extracted from the electronic medical record and analyzed utilizing descriptive statistics. Primary objectives were to quantify ASCVD risk and appropriate statin use in our population. Results Of the 158 patients included, average age was 42 years. The majority were male (89%), Black (73%), overweight/obese (117/148, 79%), on an integrase single-tablet regimen (78%), with CD4 &gt;200 cells/µL (97%), and HIV RNA &lt; 20 copies/mL (85%). Of the 18 females, 8 were transgender. Within the prior year, 65% had a lipid panel. For the 50 patients meeting criteria for 10-year ASCVD estimation, median (range) risk was 6.6% (0.8% - 31.9%). Only 12 patients were on statins. Of these, all were indicated per AHA/ACC guidelines with 10 prescribed appropriate intensity. An additional 45 patients had indications for statins but were untreated. In total, 47 patients (30%) were not receiving appropriate statin therapy. Conclusion Results of our study suggest ASCVD risk management is an area of improvement for inmates living with HIV, especially as we look towards caring for an aging HIV population. Future directions include comparing these data to data from a later time point to evaluate time for guideline uptake. Disclosures Thomas D. Chiampas, PharmD, BCPS, AAHIVP, Gilead (Employee)

scholarly journals Omega-3 Fatty Acids and Cardiovascular Disease: A Narrative Review for Pharmacists

2021 ◽  
pp. 107424842110237
Author(s):  
Dhiren Patel ◽  
Robert Busch
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Eicosapentaenoic Acid ◽  
Disease Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Icosapent Ethyl ◽  
Atherosclerotic Cardiovascular Disease Risk

Background: Atherosclerotic cardiovascular disease is a significant cause of morbidity and mortality worldwide. While use of statin therapy has improved management of lipids, an unmet need in reducing residual atherosclerotic cardiovascular disease risk and ischemic events persists. We provide an overview of the pharmacology of omega-3 fatty acids, omega-3 fatty acid cardiovascular outcomes trials, landmark clinical data and pharmacology of icosapent ethyl (a stable and highly purified ethyl ester of eicosapentaenoic acid), and the critical differences between fish oil supplements and prescription omega-3 fatty acids. Method: A PubMed literature review was conducted in April 2020 to identify articles discussing omega-3 fatty acid cardiovascular outcomes trials, pharmacology of icosapent ethyl, and the evaluation of fish oil dietary supplements and prescription omega-3 fatty acids. Results: Both eicosapentaenoic acid and docosahexaenoic acid have been widely associated with positive health benefits; however, data are inconsistent regarding the benefit of combination eicosapentaenoic acid and docosahexaenoic acid in patients with cardiovascular disease. Eicosapentaenoic acid, and specifically icosapent ethyl, has demonstrated atherosclerotic cardiovascular disease risk reduction among statin-treated patients. Important clinical differences exist between dietary supplement and prescription omega-3 fatty acid products. Conclusions: As research regarding the optimal management of dyslipidemia continues, additional therapy beyond statins is necessary to reduce atherosclerotic cardiovascular disease risk. In large cardiovascular outcomes trials, eicosapentaenoic acid has demonstrated cardiovascular benefit. Icosapent ethyl possesses a favorable efficacy and safety profile and should be considered as an adjunct to statin therapy to reduce ischemic event risk.

scholarly journals Evaluating algorithmic fairness in the presence of clinical guidelines: the case of atherosclerotic cardiovascular disease risk estimation

2021 ◽  
Author(s):  
Agata Foryciarz ◽  
Stephen R. Pfohl ◽  
Nigam Shah ◽  
Birju Patel
Keyword(s):  
Cardiovascular Disease ◽  
Disease Risk ◽  
Risk Estimation ◽  
Cardiovascular Disease Risk ◽  
False Negative ◽  
Decision Rules ◽  
Heart Association ◽  
Error Rates ◽  
Atherosclerotic Cardiovascular Disease ◽  
Ascvd Risk

The American College of Cardiology and the American Heart Association guidelines on primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend using 10-year ASCVD risk estimation models to initiate statin treatment. For guideline-concordant decision making, risk estimates need to be calibrated. However, existing models are often miscalibrated for race, ethnicity, and sex based subgroups. This study evaluates two algorithmic fairness approaches to adjust the risk estimators (group recalibration and equalized odds) for their compatibility with the assumptions underpinning the guidelines' decision rules. Using an updated Pooled Cohorts dataset, we derive unconstrained, group-recalibrated, and equalized odds-constrained versions of the 10-year ASCVD risk estimators, and compare their calibration at guideline-concordant decision thresholds. We find that, compared to the unconstrained model, group-recalibration improves calibration at one of the relevant thresholds for each group, but exacerbates differences in false positive and false negative rates between groups. An equalized odds constraint, meant to equalize error rates across groups, does so by miscalibrating the model overall and at relevant decision thresholds. Hence, because of induced miscalibration, decisions guided by risk estimators learned with an equalized odds fairness constraint are not concordant with existing guidelines. Conversely, recalibrating the model separately for each group can increase guideline compatibility, while increasing inter-group differences in error rates. As such, comparisons of error rates across groups can be misleading when guidelines recommend treating at fixed decision thresholds. The illustrated tradeoffs between satisfying a fairness criterion and retaining guideline compatibility underscore the need to evaluate models in the context of downstream interventions.

The Importance of Following ACC/AHA Cholesterol Guidelines 2013 by Residents’ Physicians to Reduce Atherosclerotic Cardiovascular Disease in Different Populations Gheith Yousif, MD/MBChB, Kevin Phelps, DO., Robert Gotfried, DO. University of Toledo/Family Medicine Department

2018 ◽  
Vol 5 ◽  
pp. 17-20
Author(s):  
Gheith Yousif ◽  
Kevin Phelps ◽  
Robert Gotfried
Keyword(s):  
Family Medicine ◽  
Success Rate ◽  
Heart Association ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Prescribing Pattern ◽  
Resident Physicians ◽  
Correct Dose ◽  
Ascvd Risk ◽  
Cholesterol Guidelines

BACKGROUND: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol protocols recommend the use of Pooled Cohort Equations to estimate 10-year and life time Atherosclerotic cardio-vascular disease (ASCVD) risk as a guide for primary prevention treatment options. Many providers underutilize this important tool.OBJECTIVES: To observe resident physicians’ HMG COA inhibitor (statins) prescribing pattern, with particular attention to appropriate dosing as per 2013 ACC/AHA Cholesterol Guidelines, at the University of Toledo Family Medicine Residency Program and to increase Resident Physicians’ awareness of the ASCVD risk calculator as a tool to improve appropriate statin dosing.METHODS: A retrospective, observational, cross-sectioned chart review was performed to analyze pre-existing data collected from a patient population within a defined time period. The study included 237 patient charts, who received care from among 12 Family Medicine Residents.RESULTS: The success rate for correct statins prescriptions for first year residents was 63%, including 24 correct dose prescriptions out of 38 patients total. Second year residents’ success rate increased to 73%, representing 58 correct dose prescriptions out of 80 patients total. Third year residents success rate was 63% with 75 correct dose prescriptions out of 119 patients total.CONCLUSION: Out of 237 chart reviewed, 157 patients received appropriately dosed statin prescriptions, representing a success rate of 66%. This suggests that across all levels of resident training, there is room of improvement in the utilization of the 2013 ACC/AHA lipid lowering guidelines.

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