ASCVD

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Adding to Statins: Achieving Optimum Reduction of “Bad” Cholesterol

Khairunnisa Semesta, MA

Atherosclerotic cardiovascular disease (ASCVD) is the number one cause of death in the Western world.[1] Since 2016, cardiovascular diseases have caused 1 in 3 deaths in the United States, and this trend is expected to continue in the future. There is a well-established relationship between ASCVD and elevated levels of low-density lipoprotein C (LDL-C), often called “bad” cholesterol because of its potential to accumulate in the blood vessels and contribute to the formation of fat plaques.[2] People with familial hypercholesterolemia (an autosomal dominant genetic disease caused by mutations in the LDLR, LDLRAP, APOB, and PCSK9 genes)[3] are also at risk for ASCVD due to their genetic predisposition to high cholesterol levels.

Currently, the standard of care is statin, a group of drugs that inhibits the HMGR enzyme, a key player in the cholesterol synthesis pathway. Over 55% patients undergo statin management to lower their LDL-C levels and consequently reduce morbidity and mortality.[4] However, 7 out of 10 patients on statins do not achieve their LDL-C goal. In addition, patients on statins still have residual risk of experiencing cardiovascular events and premature mortality.[5] This is due to multiple factors: nonadherence to statin management, which typically is consumed daily; drug intolerance due to the development of statin-associated muscle symptoms[6]; heterogeneity in response[7]; and others. As such, patients who are unable to control their cholesterol levels on maximum statin dose typically require an additional therapy.

Exploring additional therapies for patients who are unable to control their cholesterol levels on statins alone is the goal of the Add on Efficacy: Oral, Nonstatin Therapies for Lowering LDL-C Program in Scientific Sessions 2021, presented by Harold Bays, MD (Medical Director and President of the Louisville Metabolic and Atherosclerosis Research Center) and sponsored by Esperion Therapeutics. Until 2020, there was only one FDA-approved oral nonstatin therapy for ASCVD management: a drug called ezetimibe, which inhibits intestinal cholesterol absorption.[8] In 2020, bempedoic acid (Nexletol™) and bempedoic acid plus ezetimibe (Nexlizet™) were approved as adjuncts to diet and maximally tolerated statin therapy for patients with ASCVD or familial hypercholesterolemia who require additional lowering of LDL-C. Bempedoic acid inhibits ACL, a key enzyme in the cholesterol synthesis pathway. By week 12 of treatment, bempedoic acid and the combination of bempedoic acid and ezetimibe led to 17-18% and 38% and mean reduction of LDL-C, respectively, compared to patients given placebo and maximally tolerated statin dose.

Although statins have typically been the first line therapy for the management of ASCVD, current trends point to the need of developing additional and orthogonal therapies to achieve optimal LDL-C levels. To this end, multiple therapies are used clinically, including oral medications like bempedoic acid, ezetimibe, and bile acid sequestrants as well as other forms of therapeutics like PCSK9-inhibiting antibodies.[9] Beyond this session on non-statin therapies, Scientific Sessions 2021 provides other updates on current clinical management and emerging breakthroughs in cardiovascular health – make sure you tune in to other sessions on November 14-15, 2021!

Reference

[1] Nichols M, et al. (2014) Eur Heart J 35:2950–9

[2] Mihaylova, B. et al. (2012) Lancet 380:581–90

[3] Bouhairie, V. E. and Goldberg, A. C. (2015) Cardiol Clin 33.2: 169-79

[4] Bittner, V. et al, (2015) Journal of the American College of Cardiology, 66.17: 1873-1875

[5] Go, A. S., et al. (2014) Circulation 129: e28-e292

[6] Ward, N. C., et al. (2019) Circ Res 124:328–350

[7] Akyea, R. K. et al. (2019) Heart 105:975–981

[8] Miura, S. and Saku, K. (2008) Intern Med 47.13: 1165-1170

[9] Gupta, M. et al. (2020) Expert Opin investing Drugs 29(6):611-622.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

 
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Highlights of AHA18 – Bridging Lifestyle Medicine with Contemporary Medicine through Science

Renee Bullock-Palmer, MD

This year’s annual scientific meeting of the American Heart Association (AHA) held in Chicago, Illinois November 10-12, 2018 was excellent. The abbreviated 3-day meeting received positive feedback as this allowed practicing physicians to attend the meeting over the weekend and be able to return to their practice early in the work week rather than having to spend an extended time away from the office. It was great being a part of the AHA Early Career Blogger group as this allowed access to many of the embargoed sessions. At these sessions I was able to listen to the AHA 2018 updated Lipid Management Guidelines1 as well as The Physical Activity Guidelines for Americans, Second Edition2 prior to their release at the meeting. This gave me a chance to ask the guideline committee several questions related to patient management.

 

Opening Session:

The opening session by Dr. Ivor Benjamin, the President of the American Heart Association, delivered very powerful messages throughout his speech. He highlighted the track of his career and the important role of strong mentors throughout his career and the impact it had on his advancement throughout the field of cardiology. He also discussed both the importance of mentoring and diversity in the cardiology profession highlighting the fact that African American men account for only 3% of Cardiologists in the United States and the need to bridge this gap. I found this session very inspiring and encouraging especially with regards to mentoring and supporting junior colleagues and being grateful for the mentors I have had thus far in my career. I also welcomed the message of the importance of diversity and inclusion as this leads to a healthier work and training environment.

 

Bridging Lifestyle Medicine with Contemporary Medicine through Science:

This year’s meeting highlighted the value of integrating lifestyle medicine with contemporary medicine to achieve the best outcomes for patients with regards to the prevention of cardiovascular disease. This was supported by the release of the updated 2018 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines on Lipid Management on the first day of this meeting1. This updated guideline emphasized the importance of the cholesterol management at all stages of adulthood along with the importance of therapeutic lifestyle changes1. The utility of coronary artery calcium (CAC) scoring with cardiac CT was also emphasized as a useful tool to further refine patients’ risk to determine the best management for patients who are at intermediate risk for atherosclerotic cardiovascular disease (ASCVD)1. This guideline also had included ezetimibe and PCSK9 inhibitors as having a complementary role when used with statin therapy in selected patients at high risk for ASCVD1. The release of this updated guidelines will be a useful in my management of patients with regards to primary and secondary prevention of ASCVD. I appreciated the role of CAC scoring which will be very helpful for the management of the intermediate risk patients.

The release of the U.S. Department of Health and Human Services’ second edition of the Physical Activity Guidelines for Americans on the last day of the meeting was also well received2. This second edition emphasized the importance of increasing physical activity for all age ranges throughout the population including women in pregnancy and the postpartum period, as well as adults with chronic diseases or disabilities2. This guideline update will assist me with counseling patients with regards to increasing their physical activity to improve their overall cardiovascular health.

 

Networking Opportunities:

There were many networking opportunities during the meeting. These included the Council on Clinical Cardiology dinner on the first night of the meeting which honored Dr. Judith Hochman the recipient of the James B. Herrick Award for Outstanding Achievement in Clinical Cardiology. Dr. Stacy Rosen was also the recipient of the Women in Cardiology Mentoring Award. This dinner was attended by many leaders in the field of Cardiology and was a great opportunity for me to meet these leaders. The Women in Cardiology Committee also hosted a networking luncheon on the first day of the meeting during which Dr. Sharonne Hayes from the Mayo Clinic was the keynote speaker. Dr. Hayes gave a very riveting interactive talk on leadership for women in cardiology, she was also the recipient of last year’s Women in Cardiology Mentoring Award. Her talk was useful with very powerful messages on navigating your professional and personal life to achieve overall job satisfaction, career success and personal happiness. I learned several tips that I will apply to my own career as well. Dr. Annabelle Volgman and the faculty at Rush University was gracious to host a wonderful networking dinner for Women in Cardiology (WIC) on the second night of the meeting. This dinner provided a great opportunity for me to meet fellow WIC colleagues and to discuss several relevant issues related to our practice in the Cardiology field.

Social Media Coverage:

There was also a broad social media coverage of the meeting on Twitter and this was assisted by the AHA Early Bloggers writing group. I was able to share live tweets during several sessions and this generated a lot of discussion amongst members on Twitter. This also allowed many colleagues who were unable to attend the meeting to be able to follow and comment on several meeting highlights.

 

Looking Forward to AHA 2019:

This year’s AHA Scientific Sessions embrace of lifestyle medicine and the value of preventive cardiology was refreshing and empowering. This meeting highlighted the importance of not only treating ASCVD but also the importance of preventing disease and empowering our patients to take responsibility for their health as well. In the words of Goethe as mentioned in Dr. Ivor Benjamin’s opening session “Choose well….your choice is brief, and yet endless.” We look forward to next year’s AHA 2019 meeting in the beautiful city of Philadelphia.

 

References:

1. Grundy SM, Stone NJ, Bailey AL, Beam LT, Birtcher KK, et al. 2018AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. JACC Nov 2018, 25709; DOI: 10.1016/j.jacc.2018.11.003

2. The Physical Activity Guidelines for Americans: THe HHS Roadmap for an Active Healthy Nation. Second Edition. ADM Brett P. Giroir, MD.

 
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Women in the New Lipid Management Guidelines

Mirvat Alasnag, MD

The American Heart Association‘s annual meeting, Scientific Sessions, remains a Mecca for cardiologists worldwide. Those of us who were unable to attend in person followed the scientific discussions virtually through the Live Streaming option.  This year the much anticipated update to the Lipid Management Guidelines were presented at the meeting.  A focus on women as a special population was addressed separately by Dr. Lynne Braun. As cardiologists, we are not trained to search for atherosclerotic cardiovascular disease (ASCVD) enhancers specific to women, namely premature menopause (less than 40 years old), pregnancy associated disorders such as preeclampsia, gestational diabetes and preterm labor. Moreover, we often fail to discuss pregnancy and contraception with women of childbearing age who require statin therapy based on their ASCVD risk assessment. The majority of our key performance indicators in a cardiac unit or clinic require that patients are discharged on a statin if they are at risk. Yet, women should be advised to discontinue statin therapy 1-2 months prior to attempting pregnancy. It seems counter-intuitive to discuss discontinuation of statin therapy in a system that measures performance by the intensity of the prescribed dose. This in itself requires retraining of cardiologists and the AHA offered a unique opportunity to highlight its importance during Dr. Braun‘s presentation.

Another related topic addressed extensively at this year’s meeting was the role of calcium scoring (CACS) in risk stratification in the new lipid management guidelines. It is noteworthy that several large studies demonstrated that CACS improves risk assessment when combined with the conventional risk parameters.1-3 Women often have lower CACS compared to age-matched men. A meta-analysis by Kavousi et al in 2016 examined 5 large cohorts of women with an ASCVD risk <7.5% (low risk by current guidelines).4  CACS was identified in 36% of the women which led to a 2-fold increase risk of ASCVD. Ensuant to this discussion, is the topic of a coronary artery calcium score of 0 that denotes a very low risk, ie 1.1–1.5% 10-year risk of ASCVD events. This is commonly referred to as the power of zero calcium.5  The latest guidelines suggest CACS may assist in further stratifying women particularly those in the intermediate and borderline categories of risk given the older age of onset of ASCVD in women. It may also assist in the shared decision making with women of different ages and women with additional risk enhancers as discussed above.

As this year’s meeting drew to a conclusion, I’m grateful I could keep pace with the discussions on lipid management in women from the other end of the globe. More importantly, as a woman cardiologist, I was able to go to work the next morning and reevaluate the discussions I have with my female patients. For the first time, I tailored my discussion on statin therapy to the woman sitting across from me, my patient.

 

References:

  1. Paixao, A.R., Berry, J.D., Neeland, I.J. et al. Coronary artery calcification and family history of myocardial infarction in the Dallas heart study. JACC Cardiovasc Imaging. 2014; 7: 679–686
  2. Elias-Smale, S.E., Proenca, R.V., Koller, M.T. et al. Coronary calcium score improves classification of coronary heart disease risk in the elderly: the Rotterdam study. J Am Coll Cardiol. 2010; 56: 1407–1414
  3. Arad, Y., Goodman, K.J., Roth, M., Newstein, D., and Guerci, A.D. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol. 2005; 46: 158–165
  4. Kavousi, M., Desai, C.S., Ayers, C. et al. Prevalence and prognostic implications of coronary artery calcification in low-risk women: a meta-analysis. J Am Med Assoc. 2016; 316: 2126–2134
  5. Nasir, K., Bittencourt, M.S., Blaha, M.J. et al. Implications of coronary artery calcium testing among statin candidates according to american College of cardiology/american heart association cholesterol management guidelines: MESA (Multi-Ethnic study of atherosclerosis). J Am Coll Cardiol. 2015; 66: 1657–1668
  6. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol
    • Scott M. Grundy, Neil J. Stone, Alison L. Bailey, Craig Beam, Kim K. Birtcher, Roger S. Blumenthal, Lynne T. Braun, Sarah de Ferranti, Joseph Faiella-Tommasino, Daniel E. Forman, Ronald Goldberg, Paul A. Heidenreich, Mark A. Hlatky, Daniel W. Jones, Donald Lloyd-Jones, Nuria Lopez-Pajares, Chiadi E. Ndumele, Carl E. Orringer, Carmen A. Peralta, Joseph J. Saseen, Sidney C. Smith, Laurence Sperling, Salim S. Virani, Joseph Yeboah
      Journal of the American College of Cardiology Nov 2018, 25709