Serving the Underserved: Are We Overlooking HoFH Patients?

A NATIONAL LIPID ASSOCIATION ASSESSMENT

Financial Disclosure

Supported in part by Aegerion, Inc. and REGENXBIO Inc.

Background Familial hypercholesterolemia (FH) is one of the most commonly occurring

genetic disorders in the world. It is estimated that 1 in 250 Americans have heterozygous FH and about 1 in

160,000 to 300,000 have homozygous FH (HoFH). Homozygotes are often unresponsive to dietary and pharmacologic

intervention and often develop clinically significant ASCVD before reaching the age of 30.

Most FH patients remain undiagnosed and untreated.

Background The National Lipid Association (NLA) conducted a survey to evaluate the knowledge and

practice of primary care and other clinicians for patients with HoFH. These clinicians are usually the first in the healthcare community to see these patients. The initiative was led by a steering committee comprised of several NLA thought leaders:

Dean C. Karalis, MD, FACC, FNLA

G. Kees Hovingh, MD, PhD, MBA Anne C. Goldberg, MD, FNLA, FACPLinda C. Hemphill, MD, FACC, FNLA

Jerome D. Cohen, MD, FNLA

Methods An independent research and

survey vendor was used to conduct the survey.

The survey was sent out via e-mail to 14,904 medical professionals across the United States (US) from a registry of practitioners who agree to take surveys and who matched the specialty requirement.

The survey was fielded from June 26, 2018 to July 16, 2018.

A total of 504 clinicians completed the survey.

Screening Criteria• US-based based clinicians

• Currently treating patients with elevated LDL-cholesterol

• Licensed to prescribe medication

• Eligible medical disciplines: Physician

Nurse Practitioner

Physician Assistant

• Eligible specialty groups: Family Medicine

General Practice

Internal Medicine

Cardiology

Screening Criteria• US-based based clinicians

• Currently treating patients with elevated LDL-cholesterol

• Licensed to prescribe medication

• Eligible medical disciplines: Physician

Nurse Practitioner

Physician Assistant

• Eligible specialty groups: Family Medicine

General Practice

Internal Medicine

Cardiology

Northeast South Midwest West

24% 35% 23% 18%

Survey Participants by Region

Number of Respondents

48%(241)

1%(4)

4%(23)

47%(236)

Family Medicine Cardiology

General Practitioner Internal Medicine

7%(34)

85%(430)

8%(40)

Nurse Practitioner Physician

Physician Assistant

Respondent Demographics

Respondents by Medical Discipline

Over four-fifths of respondents (85%) were physicians and almost all respondents (99%) reported a medical area of practice in primary care and general medicine.

Respondents by Medical Area of Practice

12%(62)

88%(442)

Yes No

8%(39)

92%(465)

Yes No

Respondent DemographicsThe overwhelming majority of respondents do not consider themselves lipid specialists (88%) nor are they certified by the American Board of Clinical Lipidology (ABCL) or Accreditation Council for Clinical Lipidology (ACCL) (92%).

Do You Consider Yourself a Lipid Specialist?

Are You Certified by the ABCL or ACCL?

67%(338)

22%(109) 9%

(44)

Private PracticeHealth SystemInstitution/AcademicVA/Government Health SystemNone of the Above

14%(70)

56%(281)

30%(153)

Rural Suburban Urban

The majority of respondents (56%) practice in a suburban setting and two-thirds are in private practice.

Respondent Practice Information

Respondents by Practice Location Respondents by Practice Setting

1%(6)

1%(7)

59%

76%

69%

41%

24%

31%

0% 20% 40% 60% 80% 100%

Family with parent who has LDL-C ≥ 400mg/dL and all offspring have LDL-C 160-400mg/dL?

Pt(s) with treated LDL-C levels >300 mg/dL?

Pt(s) with untreated LDL-C of ≥400 mg/dL?

Yes No

Very High LDL-C in Respondent Practices

In Your Practice Do You Have:

70%

27%

16%

39%

36%

14%

34%

57%

0

100

200

300

400

500

600

First Choice Second Choice Third Choice

Refer to a SpecalistLifestyle Changes and Repeat Lipids in 6 monthsTreat with Medication

What Steps Would You Take?

53% would diagnose this as HoFH. 70% say their first step would be to treat with medication.

Diagnosis and Management of Patients with an Untreated LDL-C ≥ 400 mg/dL

7%

Num

ber o

f Res

pond

ents

2%

5%

16%

24%

53%

0 100 200 300

FCS

High Cholesteroldue to lifestyle

MixedHyperlipidemia

HeFH

HoFH

What Would Your Diagnosis Be?

Number of Respondents

68%

29%

13%

39%

42%

19%

32%

55%

0

100

200

300

400

500

600

1 2 3

Refer to a Specialist

Lifestyle Changes and Repeat Lipids in 6 Months

Adjust Medication

3%

The majority no longer recognizes HoFH but does appropriately select adjust medication as next step.

Diagnosis and Management of PatientsWith a Treated LDL-C >300 mg/dL

What Would Your Next Steps Be?

Num

ber o

f Res

pond

ents

2%

5%

20%

32%

41%

0 100 200 300

FCS

High Cholesteroldue to lifestyle

MixedHyperlipidemia

HeFH

HoFH

What Would Your Diagnosis Be?

Number of Respondents First Choice Second Choice Third Choice

Family with parent who has LDL-C >400mg/dL and all offspring have LDL-C 160-400mg/dLDiagnosis of HoFH was not improved by knowledge of elevated cholesterol levels in all offspring.

Yes

3%

5%

15%

26%

51%

0 100 200 300

FCS

High Cholesteroldue to lifestyle

MixedHyperlipidemia

HeFH

HoFH

Do you have a family where one parent has a LDL-C ≥ 400 mg/dL and all

offspring have LDL-C 160-400 mg/dL?

What Would Your Diagnosis Be (of patient(s) with an

Untreated LDL-C ≥400 mg/dL)?

1%

4%

17%

21%

57%

0 100 200 300

FCS

High Cholesteroldue to lifestyle

MixedHyperlipidemia

HeFH

HoFH

Number of Respondents Number of Respondents

What Would Your Diagnosis Be (of patient(s) with an

Untreated LDL-C ≥400 mg/dL)?

59%(297)

41%(207)

No

No Yes

Yes

67%(338)

33%(166)

Yes No

64%(218)

36%(120)

Yes No

Three-quarters of respondents have a patient that was diagnosed with HoFH, of those, 64% have a patient on a PCSK9 inhibitor.

HoFH Patient Demographics

Do You Have Patients That Have Been Diagnosed with HoFH?

Do You Have an HoFH Patient on a PCSK9 Inhibitor?

Yes

24%(81)

76%(257)

Yes No

67%(338)

33%(166)

Yes No

HoFH Patient Demographics Of the three-quarters of respondents who report having a patient diagnosed with HoFH, one-quarter (24%) have an HoFH patient on LDL-apheresis.

Do You Have Patients That Have Been Diagnosed with HoFH?

Do You Have an HoFH Patient on LDL-Apheresis?

33%(168)

24%(119)

43%(217)

LDL-C decrease 50% LDL-C <70 mg/dL

LDL-C <100 mg/dL

HoFH Patient Demographics 43% of respondents have a treatment goal of LDL-C <100 mg/dL for those HoFH patients who are free of Clinical ASCVD.

What Treatment Goal Would You Use for an HoFH Patient Who is Free of Clinical ASCVD?

57%(285)

43%(219)

Yes No

37%(105)

63%(180)

Genetic testing Clinical criteria

Yes

The majority of respondents report diagnosing a patient with HoFH. Of those, almost two-thirds (63%) used clinical criteria to diagnose.

HoFH Diagnosis and Treatment Plan

Have You Diagnosed Patients with HoFH?

What Method Did You Use to Diagnose HoFH?

53%

55%

66%

87%

90%

0 200 400 600

Non-HDL

Lipoprotein(a)

CACScoring

LDL-C

FamilyHistory

HoFH Patient Risk AssessmentRespondents use family history and LDL-C most often as the risk factors to determine CVD risk.

What Risk Factors Would You Use to Determine CVD Risk?

Number of Respondents

82%(411)

18%(93)

Yes No

HoFH Patient Risk AssessmentOver four-fifths (82%) of respondents used risk calculators to determine if patients were at high risk of ASCVD.

Would You Use Risk Calculators for Determining High Risk of ASCVD?

80%63% 60%

39%29%

17% 15% 14% 13% 11% 8% 7%

1.5

2.8

2.3

3.1

4.1

3.7

4.2 4.2

3.9

2.8

4.5

3.6

1.0

2.0

3.0

4.0

5.00

50

100

150

200

250

300

350

400

450

Highdose statin

Diet andexercise

PCSK9inhibitor

Ezetimibe Fish oil Fibrate Bile acidsequestrant

Niacin LDL-Apheresis

Low/Moderatedose statin

Plantsterols

Lomitapide

Choi

ce R

ank

# of

Res

pond

ents

Sel

ectin

g

Treatment of HoFH PatientsFour-Fifths of respondents would use high dose statins to treat HoFH patients. High dose statins were also ranked the highest of all the therapies (1.5 average).

What Would You Use to Treat HoFH Patients?

63%(320)

37%(184)

Yes No

Access to Lipid SpecialistsTwo-thirds (63%) of respondents report their practice has access to a lipid specialist.

Does Your Practice Have Access to a Lipid Specialist?

Access to Lipid Specialists by Respondents Who Do Not Consider Themselves Lipid SpecialistsAlmost two-thirds of respondents (61%) who do not consider themselves lipid specialists report their practice does have access to a lipid specialist.

12%(62)

88%(442)

Yes No

61%(269)

39%(173)

Yes No

No

Do You Consider Yourself a Lipid Specialist?

Does Your Practice Have Access to a Lipid Specialist?

29%(148)

71%(356)

Yes No

Access to LDL-Apheresis CentersLess than one-third (29%) have access to an LDL-apheresis center.

Does Your Practice Have Access to an LDL-Apheresis Center?

Patients on LDL-Apheresis by Practice Access to an LDL-Apheresis Center Access to an LDL-Apheresis Center has a major impact on whether or not a respondent has an HoFH patient on LDL-Apheresis.

NoYes 24%(81)

76%(257)

Yes No

84%(68)

16%(13)

Yes No

23%(58)

77%(199)

Yes No

Do you have an HoFH patient on LDL-apheresis?

Does Your Practice Have Access to an LDL-Apheresis Center?

Does Your Practice Have Access to an LDL-Apheresis Center?

Access to an LDL-Apheresis Center is lacking across all regions, with approximately two-thirds of respondents not having access in each of the four US Census Regions.

27%(47)

73%(128)

Yes No

29%(34)

71%(83)

Yes No

33%(40)

67%(82)

Yes No

30%(27)

70%(63)

Yes No

Access to an LDL-Apheresis Center by Region

Does Your Practice Have Access to an LDL-Apheresis

Center?

Does Your Practice Have Access to an LDL-Apheresis

Center?

Does Your Practice Have Access to an LDL-Apheresis

Center?

Does Your Practice Have Access to an LDL-Apheresis

Center?

Northeast South Midwest West

Access to an LDL-Apheresis Center by Practice Location

Access to an LDL-Apheresis Center is lacking across all locations, with rural practices having the least access.

SuburbanSuburban UrbanUrbanRuralRural

30%(84)

70%(197)

Yes No

13%(9)

87%(61)

Yes No

36%(55)

64%(98)

Yes No

Does Your Practice Have Access to an LDL-Apheresis Center?

Does Your Practice Have Access to an LDL-Apheresis Center?

Does Your Practice Have Access to an LDL-Apheresis Center?

Rural Suburban Urban

24%

54%

17%

5%

0

50

100

150

200

250

300

<18 Yrs 19-29 Yrs 30-39 Yrs >40 Yrs

20%

51%

19%

10%

0

50

100

150

200

250

300

<18 Yrs 19-29 Yrs 30-39 Yrs >40 Yrs

Age at Which Respondents Would Start HoFH Patients on LCL-C Lowering Medications

The majority of respondents would start an HoFH patient on LDL-C lowering medications at 19 to 29 years of age, for both males and females (54% and 51%, respectively).

What Age Would You Start a malePatient on LDL-C Lowering Medication?

What Age Would You Start a femalePatient on LDL-C Lowering Medication?

Num

ber o

f Res

pond

ents

Num

ber o

f Res

pond

ents

Age at Which Respondents Would Start HoFH Patients on LCL-C Lowering Medications by SpecialtyThe age at which respondents would start a patient with HoFH on LDL-C lowering medications remains consistent regardless of the respondent’s medical specialty.

13%

28%

9%

2%

11%

26%

8%

3%

0

20

40

60

80

100

120

140

160

<18 Yrs 19-29 Yrs 30-39 Yrs >40 Yrs

Family Medicine/General Practitioner

Internal Medicine/Cardiology

11%

27%

9%

4%

9%

24%

10%

6%

0

20

40

60

80

100

120

140

160

<18 Yrs 19-29 Yrs 30-39 Yrs >40 Yrs

Family Medicine / General Practitioner

Internal Medicine/Cardiology

What Age Would You Start a malePatient on LDL-C Lowering Medication?

What Age Would You Start a femalePatient on LDL-C Lowering Medication?

Num

ber o

f Res

pond

ents

Num

ber o

f Res

pond

ents

Conclusion

Many clinicians:

Do not recognize HoFH. Do not adequately treat HoFH. Do not have access to a lipid

specialist. Do not have access to a LDL-

apheresis center.

There is a need for:

More education for clinicians in recognizing and treating HoFH

Greater access to lipid specialists.

Greater access to LDL-apheresis centers.

Quick EHR Search Terms Untreated LDL-C ≥ 400 mg/dL Treated LDL-C >300 mg/dL Family history of high cholesterol Family history of premature CV disease

ReferencesGidding SS, Champagne MA, de Ferranti SD, et al. The Agenda for Familial Hypercholesterolemia. A Scientific Statement From the American Heart Association. Circulation. 2015; 132: 2167-2192. doi:10.1161/cir.0000000000000297.

Raal, FJ, Sjouke B, Hovingh GK, Isaac BF. Phenotype diversity among patients with homozygous familial hypercholesterolemia: A cohort study. Atherosclerosis. 2016; 248: 238–244. doi:10.1016/j.atherosclerosis.2016.03.009.

Sjouke B, Kusters DM, Kindt I, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype–phenotype relationship, and clinical outcome. Eur Heart J. 2015; 36: 560–565. doi:10.1093/eurheartj/ehu058.