Accreditation/Credit Designation

Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669 for 1.0 Contact Hour.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from by Amgen.

Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk

Release Date: September 28, 2018
Expiration Date: September 28, 2019
Media: Internet - based

Activity Overview

Statins have been the mainstream of hypercholesterolemia treatment for over 30 years, but clinicians now have effective nonstatin options when lipid-lowering goals are not met or when patients become statin intolerant. Besides bile acid binding resins and a cholesterol absorption inhibitor, 2 proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been available since 2015, alirocumab and evolocumab to provide a more aggressive approach to lipid-lowering.

In this Community Practice Connections™, 2 leading family-practice physicians will provide insight on statin intolerance and discuss nonstatin treatment options as well as compare and contrast indications for the PCSK9 inhibitors. Key points to incorporate PCSK9 inhibitors into clinical practice and tips to facilitate patient access will be included to readily broaden clinicians’ armamentarium of lipid-lowering treatments.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from by Amgen.

Target Audience

This continuing medical education (CME) activity is primarily intended for family physicians who treat patients with cardiovascular risk factors including hypercholesterolemia.

Educational Objectives

At the conclusion of this activity, you should be better prepared to:

  • Summarize the latest guidelines and recommendations on cholesterol management from major clinical organizations
  • Review potential cholesterol-lowering therapies beyond statins, and explain when these non-statin therapies should be considered
  • State the indications in detail for proprotein convertase subtilisin kexin type 9 inhibitor (PCSK9i) therapy

Faculty, Staff, and Planners' Disclosures

Faculty

Stephen A. Brunton
Stephen A. Brunton, MD
Adjunct Clinical Professor
Department of Pharmacy Practice
Roseman University of Health Sciences
Salt Lake City, Utah

Disclosure: No relevant financial information to disclose

Michael Cobble
Michael Cobble, MD, FNLA
Director
Canyons Medical Center
Sandy, Utah
Adjunct Faculty
University of Utah
Salt Lake City, Utah

Disclosure: Consultant: Kowa Pharmaceuticals America, Inc; Speakers Bureau: Amarin Corporation, Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc, Sanofi

The staff of Physicians' Education Resource®, LLC, (PER®) have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.

PER Pulse™ Recaps

1 of 3
Insight from Stephen A. Brunton, MD—PER Pulse™ Recap:
Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk

The online continuing medical education activity Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk discusses various aspects of treating patients with hyperlipidemia with a focus on non-statin drugs. Clinical experts Stephen A. Brunton, MD, and Michael Cobble, MD, FNLA, discuss statin intolerance, familial hypercholesterolemia, cardiovascular outcomes with PCSK9 inhibitors, and issues with patient access to PCSK9 inhibitors, as well as other topics.

This first of 3 PER Pulse™ Recaps for Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk will focus on managing patients with statin intolerance.

Statin drugs are a mainstay of pharmacotherapy for hyperlipidemia. After lifestyle modifications, statins are the first option suggested by clinical guidelines for hyperlipidemia.1,2 For some patients, however, statins may not be a viable treatment option for various reasons. Statin intolerance is an often-used but often-misunderstood term associated with patient response to statins.3,4

Because statin intolerance is usually described as the inability to tolerate at least 2 statins,5 one common misconception is that statin intolerance equates to a patient who is unable to take any statin. On the contrary, per guideline recommendations, the approach should be to find the appropriate statin for each patient.6 Many patients who experience adverse events with one statin are likely to tolerate a different statin or a different dose of the original statin. Actual statin intolerance may occur in 10% to 15% of patients,3 and myalgia symptoms can occur in up to 29% of patients.7 Properly treating patients with statin intolerance as well as those experiencing statin-related adverse effects is critical for optimizing lipid-lowering goals. Clinicians should consider changing dosages (including via alternate-day dosing) and trying multiple courses of different statins before excluding the drug class entirely from treatment options.6 In addition, clinicians should rule out any drug–drug interactions that could increase statin exposure, thus leading to increased susceptibility to adverse events such as myalgia.

When statin intolerance is an issue or if low-density lipoprotein cholesterol (LDL-C) lowering is insufficient on the maximally tolerated dose of a statin, patients may benefit from any of the many non-statin lipid-lowering drugs available. These range from ezetimibe to bile acid sequestrants to PCSK9 inhibitors. When LCL-C lowering is not optimized on the maximally tolerated statin dose, combinations of these drugs can be used to achieve LDL-C lowering goals.

References

  1. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [erratum in J Am Coll Cardiol. 2015;66(24):2812. doi: 10.1016/j.jacc.2015.11.019] [erratum in J Am Coll Cardiol. 2014;63(25 pt B):3024-3025]. J Am Coll Cardiol. 2014;63(25 pt B):2889-2934. doi: 10.1016/j.jacc.2013.11.002.
  2. Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol. 2015;9(2):129-169. doi: 10.1016/j.jacl.2015.02.003.
  3. Banach M, Rizzo M, Toth PP, et al. Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch Med Sci. 2015;1(1):1-23. doi: 10.5114/aoms.2015.49807.
  4. Algharably EA-H, Filler I, Rosenfeld S, Grabowski K, Kreutz R. Statin intolerance - a question of definition. Expert Opin Drug Saf. 2017;16(1):55-63. doi: 10.1080/14740338.2017.1238898.
  5. Alonso R, Cuevas A, Cafferata A. Diagnosis and management of statin intolerance. J Atheroscler Thromb. 2019;26(3):207-215. doi: 10.5551/jat.RV17030.
  6. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 focused update of the 2016 ACC Expert Consensus Decision Pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol. 2017;70(14):1785-1822. doi: 10.1016/j.jacc.2017.07.745.
  7. Rosenson RS, Baker SK, Jacobson TA, Kopecky SL, Parker BA, The National Lipid Association’s Muscle Safety Expert Panel. An assessment by the Statin Muscle Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(suppl 3):S58-S71. doi: 10.1016/j.jacl.2014.03.004.

“We know that statins are very effective in lowering LDL for many patients. However, we sometimes hear that patients may be statin intolerant, and there’s a lot of confusion about what that means. There’s probably about 10% of patients [who] have a problem with statins. The USAGE study [Understanding Statin Use in America and Gaps in Patient Education], published in 2012, looked at some of the issues and found that about 30% of the patients might have some myalgia, and that may be responsible for some discontinuation. Plus, there’s a lot of nonadherence in this particular therapeutic area. Or it may be that some patients don’t achieve their goal.”
—Stephen A. Brunton, MD


2 of 3
Insight from Michael Cobble, MD, FNLA—PER Pulse™ Recap:
Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk

This second of 3 PER Pulse™ Recaps for Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk focuses on making sense of lipid target goals described by current clinical practice guidelines.

Published guidelines for the treatment of hyperlipidemia have a few key commonalities, including lifestyle changes as the cornerstone of treatment and statins as the first line of pharmacotherapy. Slight differences in how lipid target goals are described and recent changes to guidelines may lead to confusion on lipid targets. The 2013 American College of Cardiology/American Heart Association guidelines shifted to a focus on reducing atherosclerotic cardiovascular disease (ASCVD) risk, whereas the 2014 National Lipid Association guidelines used target levels of low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol.1,2

As Dr Cobble, director at Canyons Medical Center in Sandy, Utah, and adjunct faculty at the University of Utah in Salt Lake City explained, although guideline changes were made, the lipid target goals can be viewed as essentially the same, just described differently. He suggests thinking about lipid-lowering goals in terms of percentages based on the level of ASCVD risk of patients. In practice, the approach could be as follows: moderate-risk patients, lower their LDL-C by 30% to 50%; high-risk and very high-risk patients, lower their LDL-C by over 50%.

Reconciling differences between established guidelines and previous iterations of guidelines is important for proper management of hyperlipidemia. Confusion about the changes among both clinicians and patients may lead to suboptimal treatment. Confirming the patient’s starting LDL-C level is important, as well, to understand how much their level has changed from baseline.

References

  1. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [erratum in J Am Coll Cardiol. 2015;66(24):2812. doi: 10.1016/j.jacc.2015.11.019] [erratum in J Am Coll Cardiol. 2014;63(25 pt B):3024-3025] J Am Coll Cardiol. 2014;63(25 pt B):2889-2934. doi: 10.1016/j.jacc.2013.11.002.
  2. Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol. 2015;9(2):129-169. doi: 10.1016/j.jacl.2015.02.003.

“I think the key point is [that] in your moderate-risk patients, you want to lower their LDL 30% to 50%. If their LDL is 150 and you lower it 30% to 50%, you’re going to get them down to around 80 or 90, under 100. If they’re very high-risk patients, that 150 needs to go over 50% down, close to 70%. If they’re diabetic, the LDL goal needs to be under 100. If you lower it 30%, it goes to 70. If you lower it 50%, it goes to 50. Some of the non-statin therapies in diabetic patients have shown benefit when you added them to a statin and got their LDL down to 50. Again, for most of your diabetic and high-risk patients, LDL reductions of 50% or more are extremely important. That’s one of the lipid goals.”
—Michael Cobble, MD, FNLA


3 of 3
Insight from Michael Cobble, MD, FNLA—PER Pulse™ Recap:
Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk

This third of 3 PER Pulse™ Recaps for the Community Practice Connections™: The Role of Non-Statin Therapies for LDL-C Lowering for Management of ASCVD Risk focuses on appropriate use of PCSK9 inhibitors.

With the introduction of alirocumab and evolocumab in 2015, a new class of hyperlipidemia drugs was established: PCSK9 inhibitors. Both drugs are monoclonal antibodies that can have profound effects on low-density lipoprotein cholesterol (LDL-C) levels. Recent clinical studies also suggest that the drugs can reduce the risks of certain atherosclerotic cardiovascular disease (ASCVD) outcomes.1,2 Updates to hyperlipidemia guidelines provide advice on appropriate use of PCSK9 inhibitors.3

In this Community Practice Connections™ segment, Dr Cobble, director at Canyons Medical Center in Sandy, Utah, and adjunct faculty at the University of Utah in Salt Lake City highlight several clinical scenarios in which PCSK9 inhibitors should be considered. Two groups of patients are prime candidates for PCSK9 inhibitors: those with homozygous familial hypercholesterolemia (HoFH) and those with heterozygous familial hypercholesterolemia (HeFH). It must be noted that both alirocumab and evolocumab are approved for use in HeFH, but only evolocumab is approved for HoFH. Patients with HeFH or HoFH are prime candidates for the drugs because these patients have exorbitantly high LDL-C levels that may be refractory to other pharmacotherapy. Other patient groups who could benefit from PCSK9 inhibitors are patients with diabetes and those with a history of ASCVD whose LDL-C is not controlled (ie, >100 mg/dL).

As biologics, the drugs have a high price tag that may affect patient access even with insurance coverage. Clinicians should be aware of strategies to ensure patient access. Prior authorization is often required, and proper documentation is critical to success with either an initial approval or an appeal.4,5 Recent changes to pricing for the PCSK9 inhibitors may aid in increasing patient access.6,7

References

  1. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713-1722. doi: 10.1056/NEJMoa1615664.
  2. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097-2107. doi: 10.1056/NEJMoa1801174.
  3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol [published online November 10, 2018]. Circulation. doi: 10.1161/CIR.0000000000000625.
  4. Kaufman TM, Duell PB, Purnell JQ, Wójcik C, Fazio S, Shapiro MD. Application of PCSK9 inhibitors in practice: challenges and opportunities. Circ Res. 2017;121(5):499-501. doi: 10.1161/CIRCRESAHA.117.311532.
  5. Kaufman TM, Warden BA, Minnier J, et al. Application of PCSK9 inhibitors in practice. Circ Res. 2019;124(1):32-37. doi: 10.1161/CIRCRESAHA.118.314191.
  6. Caffrey M. Sanofi, Regeneron to cut Praluent prices under exclusive express scripts deal that ends prior approval delays. The American Journal of Managed Care® website. ajmc.com/newsroom/sanofi-regeneron-to-cut-praluent-prices-under-exclusive-express-scripts-deal-that-ends-prior-approval-delays. Published May 1, 2018. Accessed April 26, 2019.
  7. Dangi-Garimella S. Amgen announces 60% reduction in list price of PCSK9 inhibitor evolocumab. The American Journal of Managed Care® website. ajmc.com/newsroom/amgen-announces-60-reduction-in-list-price-of-pcsk9-inhibitor-evolocumab. Published October 24, 2018. Accessed April 26, 2019.

“I think the patients [who] are most appropriate for PCSK9 inhibitor therapy would really be your very highest-risk patients. Those are going to be people with homozygous familial hypercholesterolemia. Those people will have cholesterols in the 400 to 800 range. LDLs will be 300 to 500. I’ve seen them as high as 1200. Those patients are appropriate. The heterozygous familial hypercholesterolemia patients with genetic disease, as well—they usually have cholesterol in the 300 or 400 range, with LDLs above 200. Then I think any patient with diabetes or [who] has had a vascular event—peripheral artery disease, cerebrovascular disease, cardiovascular disease—and their LDL is still above 100 despite optimal therapy [will] need at least another 50% reduction in their LDL. Again, the PCSK9 drugs will additively or independently lower LDL at least 50%, oftentimes 60% to 70% in addition to current therapy they’re on.”
—Michael Cobble, MD, FNLA


Login or Register to Start Activity

Please use the form below to Register or Log In to begin Activity.

*Required Fields
Calendar of Events
SUNMONTUESWEDTHURSFRISAT
    123
45678910
11121314151617
18192021222324
25262728293031
Filter By