The FH Foundation CASCADE FH Registry TM. CASCADE FH Registry #FHSummit15.
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Transcript of The FH Foundation CASCADE FH Registry TM. CASCADE FH Registry #FHSummit15.
The FH FoundationCASCADE FH RegistryTM
CASCADE FH Registry
#FHSummit15
Multicenter US registry to increase awareness, characterize treatment, monitor outcomes in FH
https://thefhfoundation.org/fh-research/registry/
#FHSummit15
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
#FHSummit15
Growth
Summit 2014 Summit 2015
#FHSummit15
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
#FHSummit15
Patient Demographic – Clinical Portal
#FHSummit15
Patient Demographic – Clinical Portal
#FHSummit15
*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
#FHSummit15
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)
#FHSummit15
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
#FHSummit15
Lipids
#FHSummit15
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
#FHSummit15
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%
#FHSummit15
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
#FHSummit15
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%)
#FHSummit15
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%)
#FHSummit15
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%)
#FHSummit15
Treated LDL-C Values
#FHSummit15
<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
#FHSummit15
<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.
#FHSummit15
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*
#FHSummit15
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.
#FHSummit15
Growth
Summit 2014 Summit 2015
#FHSummit15
Self-reported Quality of Life
#FHSummit15
FH Understanding (Patient Reported)
0
20
40
60
80
100
5334
5533
69
Completely Understand (%)
Completely Understand
#FHSummit15
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
#FHSummit15
Conclusions
#FHSummit15
• 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
#FHSummit15
CASCADE FH Registry Sponsorship
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