National Clinical Audit of the

Management of Familial

Hypercholesterolaemia 2010

Steve E Humphries, BHF Professor Steve E Humphries, BHF Professor Cardiovascular Genetics UCL

Kristina Pedersen, Joe Besford, Michael Roughton RCP

Structure of talk

� Introduction

� Organisational Audit - Results and Key Recommendations

� Clinical Audit of Adults - Results and Key Findings

� Clinical Audit of Children - Results and Key Findings

� Key Recommendations

Working Group

Professor Steve Humphries, Kristina Pedersen , Dr Jonathan Potter, Joseph Besford, Rhona Buckingham, Dr Chris Hendricks, Claire Neuwirth, Dr Mary Seed, Michael Roughton, Katharine Young, Jane Ingham, Professor Roger Boyle, Dr Cyril Chapman, Dr Philip Adams, Dawn Davies,Professor Andrew Neil, Dr Ian McDowell, Judy O’Sullivan, Dr Tim Wang, Dr

Devaki Nair, Dr David Wald

Steering Group

BackgroundBackground� National audit based on agreed standards and

evidence-based guidelines is expected to improve clinical practice, and thereby significantly reduce the mortality and morbidity associated with FH.

� Audit standards and indicators were developed from the NICE Clinical Guideline for the Identification and Management of FH (CG71, 2008).

� A 14 Site pilot was run in 2009 to test the methodology. This resulted in the notes of 226 adults and 22 children with FH being examined.

� On the basis of this experience the full national audit was developed.122 sites participated in the 2010 national audit. This resulted in the notes of 2324 adults and 147 children with FH being examined.

Issue date: August 2008

NICE clinical guideline 71Developed by the National Collaborating Centre for Primary Car e

Identification and management of familial hypercholesterolaemia

http://www.nice.org.uk/nicemedia/pdf/CG071

Sites Audit leadsDr Adam Cookson, Ms Cathy Havard, Dr Charles van Heyningen, Sally Hanton, Dr Michael Penney, Dr Paul Cook, Dr David Cartwright, Dr Tahseen Chowdhury, Naomi Cavanagh, Dr Sudha Iyer, Dr Michael Mulcahy, Linda Wright, Dr WS Wassif, Prof Paul Nicholls, Dr Colin Graham, Prof Ian Young, Dr Yee Ping Teoh, Dr John Harvey, Ms Petula Whittle, Dr Chris Hendriksz, Dr AnupamChakrapani, Dr Saikat Santra, Kelly Burt, Dr A Ahmed, Dr Etumi, Ms Jayne Porter, Dr Donald Whitelaw, Dr Paul Sainsbury, Dr Andrew Iversen, Prof Tim Reynolds, Mrs Alice Joy, Dr Huw Griffiths, Dr Paul Flynn, Dr Ian McDowell, Dr Alan Rees, Ms Kate Haralambos, Dr Handrean Soran, Ruth Eatough, Dr Tara Clancy, Dr Paul Masters, Ms Sarah Wright, Dr Peter Carey, Mrs Sue Russell, Dr KH Tang, Ms Katrina Estlea, Dr Shirley Bowles, Ms Mary Fisher-Morris, Dr David Cassidy, Kelly Parham, Aimee Protheroe, Dr Garry Tan, Ms Margaret Bailey, Frank Geoghegan, Dr Katherine Sloper, Sadia Siddique, Dr Adie Viljoen, Dr Peter Winocour, Ms Ann Ainsworth, Dr Manojchandra Mishra, Dr Jenny Prouten, Dr Sahnil Kadir, Mr Andrew Costello, Dr Nikhil Patel, Dr Jonathan Morrell, Ms Gemma Baldock-Apps, Dr Hervey Wilcox, Dr Niki Meston, Dr M Lapsley, Dr Tim Wang, Dr Hayley Bentley, Mrs Michelle Collins, Dr Vinod Patel, Mr David Watts, Mr Atul Kotecha, Dr Kok-Swee Gan, Dr Lara Abulhoul, Mel McSweeney, Dr Anthony Wierzbicki, Ms Zofia McMahon, Dr Martin Crook, Dr Deepak Chandrajay, Dr Mike Toop, Christina Jewkes, Dr Alan Jones, Dr Rachel Marrington, Dr Ian Walker, Razya Hussain, Dr Michelle Emery, Dr Nuha Haboubi, Ms Leah Williams, Victoria Edwards, Dr Shahenaz Walji, Yvonne Tan, Dr Martin Grimmer, Dr Patrick Twomey, Dr Taruna Likhari, Ms Tracy Hitching, Dr Ali Al-Bahrani, Charlise Cuthbert, Dr Rama Chandra, Dr Rosemary Clarke, Dr John Wong, Ms Anne Jones, Dr Martin Myers, Dr Simon Howell, Ms Alison Leather, Dr Yvette Lolin, Dr Anne Tarn, Ms Gloria Rest, Ms Jennifer Hughes, Dr Vasantha de Silva, Karen Williams, Ms Celia O'Connor, Dr Angela Gbegbaje, Dr David Oleesky, Dr Kevin Evans, Dr David Gwilt, Mrs Deborah Saberi, Dr Ceridwen Coulson, Ms O'Connor, Dr Angela Gbegbaje, Dr David Oleesky, Dr Kevin Evans, Dr David Gwilt, Mrs Deborah Saberi, Dr Ceridwen Coulson, Ms Christine Tinline-Purvis, Dr Chris Lord, Mrs Margaret Bowe, Dr John Frater, Mr Terry Holdcroft, Dr Fiona Gidden, Karen Tiwary, Dr Alastair Watt, Dr Michael Ryan, Dr Elinor Hannah, Dr Paul McKenna, Deborah Stone, Dr Peter Prinsloo, Mr Gareth Tomlinson, Dr Fredrik Karpe, Ms Katerina Vernicos, Dr Deepak Bhatnagar, Dr Steven Martin, Dr Hannah Delaney, Dr Aabha Sharma, Dr Jose Cabrera-Abreu, Dr N Pritchard, Ms Vivienne McGlashan, Dr Andrew Hutchesson, Dr Suzanne Palin, Ms Angela Chicamisse, Dr Mahmoud Barbir, Alison Pottle, Jane Breen, Dr Simon Fleming, Dr Maurice Salzman, Ms Jane Morgan, Ms Lesley Holman, Joanne Lowe, Dr Devaki Nair, Mr Darren Harvey, Dr A Jain, Malin Zettergren, Dr Lakshminaraya Rao Ranganath, Ms Helen Brady, Dr CallumLivingstone, Lesley Snell, Dr Andrew Taylor, Dr Felicity Stewart, Dr Aram Rudenski, Ms Helen Walsh, Dr Nuala O'Connell, Dr Elizabeth Hughes, Dr Inessa Tracey, Ms Rose Bedward, Dr Mark Sharrard, Lesley Edgar, Dr Trevor Gray, Dr Catherine Bywaters, Roger Marr, Dr Firial Al-Ubaidi, Ms Sonia Gill, Dr Nigel Capps, Mrs Sally Allen, Dr Ian Bailey, Dr Sath Nag, Ms Maria TaylorDr Atif MunirDr Emmanuel AbuDr Peter SharpeDr Charles van HeyningenMeryl AndersenDr Mourad LabibDr Angela Haddon, Ms Liz Higginson, Dr Michael Mansfield, Amalia Iliopoulou, Julian Barth, Dr Martin Crook, Sarah Goreham, Carol Houbert, Ms Clare Holtby, Dr Paul Brooksby, Dr Ryan D'Costa, Ms Maxine Andrews, Fiona Dudley, Dr Dermot Neely, Lesley Srembridge, Dr Yetunde Baoku, Dr Shanthi Thomas, Dr Adrian Jennings, Ms Paula Bennett, Dr Robert Lord, Dr Joe Begley, Prof Rousseau Gama, Dr Lance Sandle, Stuart Logan, Dr Koshy Jacob, Dr Catherine Lunken, Mr Chris North, Prof Gordon Ferns, Dr Basil Issa, Dr Ahmed Elsadig, Dr Robert Cramb, Dr Takek Hiwot, Dr Helen Ashby, Dr Graham Bayly, Ms Isabella To, Dr Mike Khan, Dr Sethsiri Wijeratne, Mrs Linda Belgrove, Dr Hala Alsafadi, Dr Webster Madira, Dr Maciej Tomaszewski, Ms Julie Bennett, Dr Paul Giles, Susan Smith, Dr Alison Davis, Mr R Cottier

ParticipationParticipation

�� 137/145 sites signed up for the audit (94%)137/145 sites signed up for the audit (94%)

�� 118 sites completed the organisational survey (81%) 118 sites completed the organisational survey (81%)

England (108), Wales (6), Scotland (4) and Northern England (108), Wales (6), Scotland (4) and Northern

Ireland (4)Ireland (4)

�� Data were supplied for 2471 patients Data were supplied for 2471 patients (3(3rdrd Clinic visit)Clinic visit)

�� Sites supplied data on one or both groups of patients Sites supplied data on one or both groups of patients

(adults and children). (adults and children).

�� 2324 adults (94%)2324 adults (94%)

�� 147 children (6%) 147 children (6%)

Since ~15,000 FH patients currently identified in UK this is

~15% of adults and 30% of children so likely to be

good representation of current practice

Where are FH patients being seen in the 118 sites?

Organisational Audit – Key Results - 1

Diab/Endoc

24%

General

Med

13%

Specialist

Med

2%

Other

3%

As with 2008 Heart UK survey, FH patients are managed in manydirectorates, mostly Chemical Pathology, Diabetes and Cardiology.

Cardiology

11%Chem Path

47%

� Majority have a lead clinician responsible for FH care, <50%have someone with operational managerial responsibility forFH service

� Most sites do not run a dedicated FH clinic.

� 19% report not using the Simon Broome Diagnostic criteria

Organisational Audit – Key Results - 2

� Only 26% of sites have a specialist service for young peoplewith FH.

� Over 60% of sites have neither a paper or electronic databasefor FH patients.

As expected – Room for improvement!

Country Comparisons

120

DNA Test CT Commis

Organisational Audit – Key Results - 3

� Only 12% of sites have a designated cascade testing clinic, with another 14% in development of this service.

� While 57% of sites have DNA testing available this is funded onlyin 12% of sites

DNA and CT commissioning is

lagging behindin England

2131

100

66

5

25

8375

0

20

40

60

80

100

120

England Wales North I Scotland

Per

cen

tage

Shared Care Arrangements

8590

Formal Informal None

Organisational Audit – Key Results - 4

Formal shared care arrangements are important if FH patients are discharged to GPs, develop CHD, or are women of child bearing age that have been detected by cascade testing

Most sites do nothave adequate shared care

arrangements6 5

1

129

50

43

14

36

12

44

52

85

52

79

0

10

20

30

40

50

60

70

80

90

GPs Cardiology Obstetrics Pediatrics LDL-apher

Pe

rcen

tage

Organisational Audit – Key Results - 5

� On average sites reported 1 consultant PA/wk for lipid management, of

which 35% is spent on FH patients.

� 86% of sites had no lipid specialist Nurse

Number Consultant PAs Number Nurses

Many sites are a single Consultant and no Nurse

Organisational Audit – Key Results - 6

� Median number of New FH patients seen last year was 20 (IQR 7-50)

� Median number FH patients in follow up was 50 (IQR 20-140)

Number New Adult Patients Number Adult Patients in Follow-up

Total = 4276 Total = 11065

Many small and some large sitesOverall ~15,000 FH patients currently being seen

� Organisational aspects of the care pathway for FH are still being developed.

� Current resources are inadequate to cope with the identification of thepredicted FH relatives of affected cases UK wide. This includes accessto trained staff (86% of sites had no lipid specialist nurses), IT provision and pedigree drawing.

Organisational Audit - Key Findings

and pedigree drawing.

� There is a major lack of family “cascade” testing, whether carried out on the basis of lipid levels or, more effectively, by a DNA diagnosis.

� While there is good access to DNA diagnosis and funding for DNA testing in the Devolved Countries, access and funding in England is poor.

� Commissioning arrangements need urgently to be reviewed for key elements of the services for FH patients, both at national and local levels.

� Several aspects of the care pathways for FH patients need to be implemented, including shared care arrangements between hospital andprimary care and better links between with several other specialties, including paediatrics.

�

Organisational Audit Key Recommendations

� Additional resources will be needed to cope with the care of new FH patients identified by cascade testing. Training to address the shortage ofstaff with key skills will be required.

� Systems need to be developed and implemented to carry out comprehensive “cascade” testing. This will require trained health professionals with the appropriate skills to follow up the families of indexpatients, improved IT resources, including an FH patient database, and pedigree drawing.

Patient data – Characteristics

• 2324 adults mean age 52.3 (42-61) yrs, %age Male = 42%

• Ethnic mix W = 83%, IA = 5%, other = 3%

• DFH : PFH : HOZ, 36% vs 58% vs 2%

• History CHD 24%, ECG in 48% notes

• 15% current 23% ex smokers

Clinical Audit – Key Results

! ?

• 15% current 23% ex smokers

• Pedigree in 91% notes, Age onset relatives CHD in 79%

• DNA testing in 27%, CT initiated in 72%

• Secondary Causes excluded, all >90%

• Annual Review performed in 82%

Characteristics as expected, Room for improvement for DNA and Cascade Testing

Are SB diagnostic criteria being properly applied?

Pre Treatment Lipoprotein measurements (adultsPre Treatment Lipoprotein measurements (adults))

LDL-C - 6.1 (5.1-7.2) HDL-C - 1.3 (1.1-1.6) TG - 1.6 (1.1-2.1)

Median (IQR)mmol/l

Not all sites use SB criteria

9% have LDL-C below4.9mmol/l SB cut-off.

Already treated by GP?

Some have TG above SB cut-off.

May be FCH?

How Many HOZ FH patients audited?How Many HOZ FH patients audited?

Baseline T-Chol

Not all sites use SB criteria !!

49 HOZ??? Expect perhaps 4-6

5 have LDL-C above SB cut-off.

All between 20-30years, only 1 had CHD.

On On -- Treatment LDLTreatment LDL--C levelsC levels

LDL-C - 3.5 (2.8-4.7) mmol/l Some patients have gone up!!

35% Atorva, 35% Rosuva, 8% Simva, 3% Prava, 14% on None* 48% also on Ezetemibe, 6% also on fibrates

44% achieved 50% lowering44% achieved 50% lowering44% achieved 50% lowering44% achieved 50% lowering20% had LDL > 4mmol/l,20% had LDL > 4mmol/l,20% had LDL > 4mmol/l,20% had LDL > 4mmol/l,8% had LDL > 5mmol/l. 8% had LDL > 5mmol/l. 8% had LDL > 5mmol/l. 8% had LDL > 5mmol/l. Mean reduction for individual patients = 39% (16%-56%)

LDL-C lowering not reaching NICE targetSince only 3rd visit some further falls may occur

8% had LDL > 5mmol/l. 8% had LDL > 5mmol/l. 8% had LDL > 5mmol/l. 8% had LDL > 5mmol/l.

Intolerant = 48%,

Declined = 13%,

Pregnant = 12%

*

Is management similar in large and small sites?

Compared 62 sites with 1 or less consultant PA/wk and 60 sites with >1

84

62

79

64

93

75

84

80

100

Small Large

*

**

p < 0.05*

Many elements not different but

On average, small sites currently lagging behindlarge sites for some NICE recomendations

2219

62

18

44

64

33

14

44

0

20

40

60

Genetic

input

Dietician Pedigree CT started Annual

review

No statin 50% Red'n

Pe

rce

nta

ge

*

*

FH Clinic

3%

Pediatric

Clinic

5%

Other

22%

Audit data for Children (<16yrs)

Where were Children seen?• 59% of sites see children

• 26% sites have a special service

for young people with FH

Many seen in adult clinics

Lipid Clinic

70%

5%

• 320 new child patients seen/yr

• 772 child patients in follow-up

Many seen in adult clinics

Over 1000 children being seen is encouraging

But number <16yrs with FH estimated to be >20,000

Audit data for Children (<16yrs)

Patient data – Characteristics

• 147 children, mean age 12.6 years, %age Male = 57%

• DFH : PFH : HOZ = 54% vs 46% vs 0.7%

• History CHD 4%

• Pedigree in 83% notes, 78% blood relatives with CHD

Children data collection good

Lipid levels?

• Pedigree in 83% notes, 78% blood relatives with CHD

• DNA testing in 52%

• Secondary Causes, excluded all >50%

• Height and Weight recorded in >90% cases

• Annual Review 96% (82%)

√

Children PreChildren Pre--Treatment Lipid levels Treatment Lipid levels Median (IQR)mmol/l

LDL-C - 5.4 (4.5-6.1) HDL-C - 1.3 (1.1-1.6) TG - 0.9 (0.7-1.2)

Levels as expected. Treatment?

13% have LDL-Cbelow SB

4.0mmol/l cut-off.

Treatments

Post Treatment LDLPost Treatment LDL--C C

Atorva

29%

Prava

None

44%

No Statin (n = 64)

Intolerant

3%

Low risk

16%

Declined

17%Other

There are no NICE Guidelines for lipid lowering in children

Prava

12%

Simva

15%

Resin 5%, Ezetimibe 2%

Fibrate 0.5%, NA 0.5%

Other

64%

Post Treatment LDLPost Treatment LDL--C C Median (IQR)mmol/l

LDL-C - 3.9 (3.4-4.8) mmol/l Statin treated children only

Median (IQR) reduction for individual patients was 31% (16-46%)

Since only 3rd visit some further falls may occur

� While good management of FH patients is occurring in both small andlarge sites, there is some evidence that small sites adhere less fully

Key Findings

� The clinical management in lipid clinics is of a good standard for individual patients who have been diagnosed with FH.

� Lipid lowering therapy is not yet optimal (8% still LDL-C > 5.0mmol/l)

Adults

large sites, there is some evidence that small sites adhere less fully to key aspects of the guideline. (annual review, pedigree data and initiation of cascade testing).

� There is a shortfall in child-focused services throughout the country,with only 26% of sites offering paediatric FH services.

� Where such services were audited they are of a good standard.

Children

� The establishment of multidisciplinary teams should be encouraged sincethey appear to achieve better implementation of the guidelines and management of FH patients.

� Resources are needed for DNA diagnosis and Clinical Genetics input.

� Based on published data, cascade testing alone will find less than 50% ofthe predicted 100,000 unidentified FH patients in the UK, and other methods for finding FH probands will need to be explored.

Key Recommendations

methods for finding FH probands will need to be explored.

National Organisations:

� Given that FH families are geographically dispersed, cascade testing maybe facilitated by a specifically funded UK FH Register to which all FH cases would be notified

� It is recommended that a second UK wide audit of services should be commissioned to start in 2012.