The FH FoundationCASCADE FH RegistryTM

CASCADE FH Registry

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Multicenter US registry to increase awareness, characterize treatment, monitor outcomes in FH

https://thefhfoundation.org/fh-research/registry/

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CASCADE FH Registry

O’Brien. Am Heart J 2014;167:342

Lipid Clinic Patient Portal

Eligibility • Clinical or genetic diagnosis of FH

Data collection • Prospective/retrospective• Entered by research staff• Abstracted from medical

records from routine care

• Prospective• Entered by patient, with

follow-up verification by research staff

Data captured • Demographics• Familial hypercholesterolemia diagnosis• Cardiovascular history• Family history• Medications• Physical examination• Laboratory studies

CASCADE-FH Registry Design

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Growth

Summit 2014 Summit 2015

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Patient Enrollment

CA(28)

GA(10)

NC(4)

NY(8)

U Penn

deGoma, 356

Thomas Jefferson

Duffy, Whellan, 44

Nemours

Gidding, 36

Stanford -Knowles,

108

Baylor

Ballantyne, 118

UT Southwestern

Ahmad, 312

The University of Kansas

Moriarty, 504 WVU

Neal, 68

Oregon Health & Science University –

Shapiro/Duell, 238

Vanderbilt

Linton, 239

Preventive Cardiology Inc.

Baum, 41

ULCA-Watson, 3

UC IrvineWong, 1

Duke

NYUUnderberg, 5

Rogosin

Hudgins, 66

MGH

Hemphill, 33

JHU

Ohio State

GeisingerBoston

Childrens

Atlantic

MayoKullo, 0

UCSF

Chicago

Maine

Lancaster

Anderson, 40

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Patient Demographic – Clinical Portal

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Patient Demographic – Clinical Portal

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*MEDPED denotes Make Early Diagnosis, Prevent Early Death; DLCN Dutch Lipid Clinic Network

Data are being refined

Diagnostic criteria

Clinica

l Diagn

osis

MEDPED

Simon-B

roome

DLCN

Other

Multiple

Mutation positi

ve0

102030405060

Series1

Patients enrolled in the CASCADE-FH Registry through one of 14 participating lipid centers (n=1565)

Excluded patients (n=270) due to:• Below 18 years of age (n=202) • Homozygous FH (n=43)• Missing statin dosage (n=25)

Adult patients with heFH eligible for analysis of cardiovascular status and treatment patterns treated at one of 11 lipid centers (n=1295)

Insights from initial characterization

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Exclusion criteria for initial characterization of of adult HeFH patients

Excluded patients not on lipid-lowering therapy or missing entry LDL-C data (n=211)

Treated adult patients with heFH eligible for analysis of goal attainment of ≥50% LDL-C reduction (n=652)

Treated adult patients with heFH eligible for analysis of goal attainment of treated LDL-C<100 mg/dl (n=1084)

Excluded patients missing untreated LDL-C data or with the same LDL-C value recorded at both time points (n=432)

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Demographics

Age at enrollment, years, median (IQR), n=1265

57 (43-66)

Female, % 59Ethnicity, %

White 80Black 7Hispanic 2Other 10

Late Diagnosis and Treatment

0 10 20 30 40 50AGE

DIAGNOSISCASCADE-FH

47Guidelines*

2-11

TREATMENT 39CASCADE-FH

21ACC/AHA

Adult Guidelines

8-10Statin

• American Association of Pediatrics 2008• US National Lipid Association 2011• International FH Foundation 2011• European Atherosclerosis Society 2013

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Lipids

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Untreated Total cholesterol mg/dl, n=949 329LDL-C, n=888 239

Treated Total cholesterol, n=1097 215LDL-C, n=1084 134Triglycerides, n=1092 113HDL-C, n=1096 52

‘Untreated’ LDL-C: highest documented values prior to initiation of drug therapy or occasionally when a patient was on a drug holiday

‘Treated’ LDL-C: most recent values available at the time of inclusion into the CASCADE-FH Registry among patients on LDL-lowering medication(s)

Additional CHD Risk Factors

Additional CHD risk factors  0 39%1 38%2 16%3+ 7%

Diabetes, n=1280 13%Current smoker, n=1272 7%Hypertension, n=1283 43%Low HDL-C, n=1285 31%Obesity, n=1223 32%BMI, kg/m2, median, n=1223 27

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Cardiovascular Disease

ASCVD, n=1273 38%Age at onset, years 52

CHD, overall cohort 36%Age at onset, years 51

CHD, men 47%Age at onset, years 47

CHD, women 29%Age at onset, years 55

Stroke or TIA, n=1282 5%Aortic valve disease, n=1284 3%

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Statin-treatedn=969

Not statin-treated n=326, 25% of overall

Statin intensity† High 544 (56%) -Low/Moderate 425 (44%) -No statin - 326 (100%)

Statin Rosuvastatin 475 (49%) -Atorvastatin 334 (35%) -

Non-statin Ezetimibe 438 (45%)* 82 (25%) Bile acid sequestrant 141 (15%) 48 (15%)Niacin 135 (14%)* 30 (9%)Fibrate 44 (5%) 20 (6%)

Statin and Non-Statin Medications

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Reasons for sub-maximal statin use

• Statin intolerance or allergy (60%)

• Patient preference (11%)

• Physician preference (11%)

• Pregnancy (3%)

• Cost (1%)

• Clinical trial participation (1%)

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Combination Therapy & Apheresis

 Statin-treated

n=969Not statin-treated

n=326Statin + ezetimibe 438 (45%) -LDL-lowering meds*

0 0 196 (60%)1 428 (44%) 87 (27%)2 353 (36%) 36 (11%)3+ 188 (19%) 7 (2%)

Apheresis* 37 (4%) 40 (12%)

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Treated LDL-C Values & Reduction

Statin-treated Not statin-treatedTreated LDL-C* n=959 n=125

<70 mg/dl 58 (6%) 5 (4%)70-99 mg/dl 194 (20%) 11 (9%)100-129 mg/dl 238 (25%) 7 (6%)130-159 mg/dl 153 (16%) 35 (28%)160-189 mg/dl 113 (12%) 22 (18%)≥190 mg/dl 203 (21%) 45 (36%)

LDL-C reduction* n=576 n=76≥50% 257 (45%) 9 (12%)

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Treated LDL-C Values

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<70 70-99

100-

129

130-

159

160-

189

190-

219

220-

249

250-

279

280-

309

310-

339

340-

369

370-

399

400+

0%

5%

10%

15%

20%

25%

30%On non-statin therapy

On statin therapy ± non-statin therapy

Treated LDL-C (mg/dl)

Magnitude of LDL-C Reduction

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<30% 30-50% >50%0%

10%

20%

30%

40%

50%

60% 55%

33%

12%

23%33%

44%

On non-statin therapy

On statin therapy ± non-statin therapy

LDL-C reduction, treated vs untreated

High Prevalence of CHD

Men Women Men Women0%

25%

50%

75%

100%

6% 6%

47%

29%

5-7-Fold Higher

US NHANES

US CASCADE-FH

AHA Heart Disease and Stroke Statistics 2014 Update: NHANES 2007-2010 prevalence of CHD age 40-59.

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Importance of CHD Risk Factors

≥2

≥1

0% 25% 50% 75% 100%

24%

61%RiskFactors

Prevalence Unadjusted OR Adjusted OR

Hypertension 43% 5.4 (4.2-6.9) 2.7 (1.9-3.8)

Diabetes 13% 4.0 (2.8-5.6) 1.7 (1.0-2.7)

Low HDL-C 31% 1.6 (1.3-2.1) 1.5 (1.1-2.1)

Smoking 7% 1.6 (1.1-2.5) 1.4 (0.7-2.5)#FHSummit15

High Prevalence of CHD (Global)

0%

25%

50%36% 33%

27%18% 17% 14% 12%

* Prevalence of ASCVD. Allard Lipids in Health and Disease 2014;13:65. Benn JCEM 2012;97:3956. Beliard Atherosclerosis 2014;234:136. Pijlman Atherosclerosis 2010;209:189. Mata Lipids in Health and Disease 2011;10:94. Hadfield Annals Clin Biochem 2008;45:199.

Age 57 59 61 51 50 46 46LDL-C 239 251 262 259 258 192 TC 389

LDL-C 134 182 - 128 124 - 194

CASCADE-FH Denmark2012

Canada2014*

UK2008

Netherlands2010*

Spain2011*

France2011*

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Goal attainment

0%

50%

100%

30%

25%

21%

0%

50%

100% 64% 41

%

60%

CASCADE-FHUK 2008 Netherlands 2010

Treated LDL-C<100 mg/dl

Reduction in LDL-C≥50%

Pijlman Atherosclerosis 2010;209:189. Hadfield Annals Clin Biochem 2008;45:199.

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Growth

Summit 2014 Summit 2015

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Self-reported Quality of Life

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FH Understanding (Patient Reported)

0

20

40

60

80

100

5334

5533

69

Completely Understand (%)

Completely Understand

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More patient-centric data needed

Limited data on non-White populations, more generalizablity

More longitudinal data needed

Track effects as PCSK9 are introduced

Integrate more historical data

Launch patient portal V2.0

More sites, more patients from diverse backgrounds and areas of the country, leverage EHR data

Convert retrospective to prospective enrollment

Get updated snapshot so we can see what happens within 1 year of FDA approval

MEDPED integration

Gaps and future plans

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Conclusions

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• High CHD prevalence among adult FH patients• Poor LDL goal attainment (<100 mg/dl, >50%) • Opportunities to improve care of FH patients:

- Early diagnosis of FH- Early initiation of LDL-lowering therapy- Use of high-intensity statin therapy- Use of combination therapy- Management of other risk factors- Careful elicitation of family history

• Please contribute to the CASCADE-FH Registry!

Publications Committee and site PIs for CASCADE FH• Zahid S. Ahmad, MD*• Emily O’Brien, PhD• Iris Kindt, MD, MPH• Peter Shrader, PhD• Joshua W. Knowles, MD, PhD• Patrick M. Moriarty, MD• Connie B. Newman, MD• Yashashwi Pokharel, MD, MSCR• Seth J. Baum, MD• Linda C. Hemphill, MD• Lisa C. Hudgins, MD• Catherine D. Ahmed, MBA• Samuel S. Gidding, MD• Danielle Duffy, MD• William Neal, MD• Katherine Wilemon, BS• Matthew T. Roe, MD, MHS

• Daniel J. Rader, MD• Christie M. Ballantyne, MD• MacRae F. Linton, MD• P. Barton Duell, MD• Michael D. Shapiro, MD

University of Pennsylvania• Tracey Sikora, Kristen Dilzell• Anna Raper, Joyce Ross

UT Southwestern• Chandna Vasandani

Stanford University• Aleks Pavlovic

Vanderbilt University• Misty Hale, Beth Medor

Oregon Health & Science University• Jill Rose

Our FH patients, family, and friends

Acknowledgments

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CASCADE FH Registry Sponsorship

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