1. Familial hypercholesterolaemia
Implementing NICE guidance
This slide set was updated in January 2012 and includes details of related guidance, NHS Evidence and NICE Pathways. The NICE Guideline has not changed.
ABOUT THIS PRESENTATION:
This presentation has been written to help you raise awareness of the NICE clinical guideline on familial hypercholesterolaemia (FH). This guideline has been written for GPs, nurses, consultants, dietitians and other staff who care for people with familial hypercholesterolaemia.
The guideline is available in a number of formats which you can download these from the NICE website.
You can add your own organisation’s logo alongside the NICE logo. We have included notes for presenters to help highlight key points to raise in your presentation and to provide supplementary information to the slides. Where necessary, the recommendation will be given in full. Please feel free to adapt, amend or remove these as you see necessary.
DISCLAIMER
This slide set is an implementation tool and should be used alongside the published guidance. This information does not supersede or replace the guidance itself.
PROMOTING EQUALITY
Implementation of this guidance is the responsibility of local commissioners and/or providers. Commissioners and providers are reminded that it is their responsibility to implement the guidance, in their local context, in light of their duties to avoid unlawful discrimination and to have regard to promoting equality of opportunity. Nothing in this guidance should be interpreted in a way which would be inconsistent with compliance with those duties.
2nd. edition – January 2012
NICE clinical guideline 71

2. Guideline review Guideline issue date: August 2008
First review: August 2011
Review recommendation:
The guideline should not be updated at this time.
NOTES FOR PRESENTERS:
The review concluded that no new evidence was identified which would invalidate or change the direction of current guideline recommendations. However, GDG members highlighted relevant ongoing research which is likely to inform future reviews of the guideline. In addition, technology appraisal guidance 132 ‘Ezetimibe for the treatment of primary (heterozygousfamilial and non-familial) hypercholesterolaemia’ is currently scheduled to undergo a review in October A decision to update this technology appraisal in the future may have an impact on the guideline recommendations and would need to be taken into consideration.
Information gathered as part of the review supported the development of the CG71 Implementation advice which was published in January This advice focuses on providing information and support for those responsible for implementing the DNA cascade testing for FH recommendations. The implementation advice can be accessed from the CG71 guideline webpage
The full guideline review report can be accessed from

3. What this presentation covers
Definitions
Background
Scope
Key priorities for implementation
Costs and savings
NHS Evidence and NICE Pathways
Discussion
Find out more
NOTES FOR PRESENTERS:
In this presentation we will start by providing a definition of the guideline scope and why it is important.
The NICE guideline contains five key priority areas and within these there are ten recommendations.
Costs and savings that are likely to be incurred in implementing the guideline are summarised, followed by a suggested list of questions to help prompt discussion.
Following this we will highlight the NICE Pathway and look at NHS Evidence.
Information on how to find out more about the support provided by NICE is given at the end of this presentation.

4. Definitions Cascade testing First-degree relative
Index individual (case)/proband
Lipid measurements/concentrations
Mutation
Second-degree relative
Tendon xanthomata
Third-degree relative
NOTES FOR PRESENTERS:
Cascade testing: A mechanism for identifying people at risk of a genetic condition by a process of family tracing. For FH the test employed is measurement (calculation) of low-density lipoprotein cholesterol (LDL-C) in the blood, and/or a DNA test if a disease-causing mutation has been identified in the index individual/proband (see below).
First-degree relative: A person’s biological parents, brothers and sisters, and children.
Index individual (case)/proband: The original patient who is the starting point for follow-up of other members of a family when investigating possible genetic factors of the presenting condition. In this document the index will be defined as such because they meet the diagnostic criteria for either definite or possible FH.
Lipid measurements/concentrations: Measurement of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). LDL-C is not usually measured directly but calculated from the total cholesterol, triglycerides and HDL-C, ideally using a fasting sample. Tests are usually done in a clinical biochemistry laboratory.
Mutation: An identified change in the DNA sequence of a gene that is predicted to damage the normal function of the gene and so cause disease.
Second-degree relative: A person’s biological grandparent, grandchild, uncle, aunt, niece, nephew, half sister or half brother.
Tendon xanthomata: A clinically detectable nodularity and/or thickening of the tendons caused by infiltration with lipid-laden histiocytes (macrophages in connective tissue). This is a distinctive feature of FH. It most frequently affects the Achilles tendons but can also the back of the hands, elbows and knees.
Third-degree relative: A person’s biological great grandparent, great grandchild, great aunt, great uncle, first cousin, grand nephew or grand niece.
Urgent referral: for the purpose of this guideline, urgent referral is as soon as possible within a maximum of 14 days
Please see appendix D of the NICE guideline for further definitions of: Adults with FH, Children/young people, Child-focuses setting, Family history, Heterozygous, High intensity statin, Homozygous, Pedigree, Premature Coronary heart disease, Proband, Simon Broome Criteria, Specialist and Specialist centre

5. Background Familial Hypercholesteroaemia (FH)
High cholesterol in the blood is caused by an inherited genetic defect
Raised cholesterol is present from birth and may lead to early development of atheroscleriosis and coronary heart disease
Siblings and children of a person with FH have 50% risk of inheriting FH
Prevalence in UK population is estimate to be 1 in 500 people, meaning approximately 110,000 are affected
NOTES FOR PRESENTERS:
Key points to raise:
In some people, a high cholesterol concentration in the blood is caused by an inherited genetic defect known as familial hypercholesterolaemia (FH).
A raised cholesterol concentration in the blood is present from birth and may lead to early development of atherosclerosis and coronary heart disease.
The disease is transmitted from generation to generation in such a way that siblings and children of a person with FH have a 50% risk of inheriting FH.
Most people with FH have inherited a defective gene for FH from only one parent and are therefore heterozygous.
Rarely, a person will inherit a genetic defect from both parents and will have homozygous FH or compound heterozygous FH.
The prevalence of heterozygous FH in the UK population is estimated to be 1 in 500, which means that approximately 110,000 people are affected. The elevated serum cholesterol concentration that characterises heterozygous FH leads to a greater than 50% risk of coronary heart disease in men by the age of 50 years and at least 30% in women by the age of 60 years.
Homozygous FH is rare, with symptoms appearing in childhood, and is associated with early death from coronary heart disease. Homozygous FH has an incidence of approximately one case per one million.

6. Scope
This guideline offers best practice advice on the identification and care of people with FH
The guideline covers:
Heterozygous and homozygous familial hypercholesterolaemia in adults and children.
Identification, diagnostic testing and management.
Primary, secondary and tertiary care settings.
NOTES FOR PRESENTERS:
Key points to raise:
This guideline offers best practice advice on the identification and care of people with FH
Groups that have been covered
Adults and children with heterozygous FH.
Adults and children with homozygous FH.
Groups that have not been covered
People with secondary hyperlipidaemia.
People with polygenic and combined hyperlipidaemia.
People with hypertriglyceridaemia and type III hyperlipoproteinaemia.
Children with other abnormalities of lipid metabolism, such as sitosterolaemia or Phytosterolaemia.
The guidance is applicable to the following settings:
Primary, secondary or tertiary care settings dealing with case identification, diagnostic testing and the management of heterozygous FH in adults and children
Tertiary care for the rare condition of homozygous FH in all age groups.

7. Key priorities for implementation
Diagnosis
Identifying people with FH using cascade testing
Management
Information needs and support
Ongoing assessment and monitoring
NOTES FOR PRESENTERS:
The NICE guideline contains 109 of recommendations about how care can be improved, but the experts who wrote the guideline have chosen key recommendations that they think will have the greatest impact on care and are the most important priorities for implementation. They are divided into five areas of key priority and within these there are ten recommendations that we will consider in turn.

8. Diagnosis
Always take a family history of premature coronary heart disease.
In children, by the age of 10 years:
offer a DNA test if the family mutation is known
measure LDL-C concentration if the family mutation is not known.
Do not use coronary heart disease risk estimation tools such as those based on the Framingham algorithm.
NOTES FOR PRESENTERS:
Recommendations in full:
A family history of premature coronary heart disease should always be assessed in a person being considered for a diagnosis of FH (see Simon Broome criteria, appendix E NICE guideline). [1.1.8]
In children at risk of FH because of one affected parent, the following diagnostic tests should be carried out by the age of 10 years or at the earliest opportunity thereafter.
A DNA test if the family mutation is known.
LDL-C concentration measurement if the family mutation is not known. When excluding a diagnosis of FH a further LDL-C measurement should be repeated after puberty because LDL-C concentrations change during puberty. [1.1.15]
Coronary heart disease risk estimation tools such as those based on the Framingham algorithm should not be used because people with FH are already at a high risk of premature coronary heart disease. [1.1.11]
Related recommendations:
Healthcare professionals should consider the possibility of FH in adults with raised cholesterol (total cholesterol typically greater than 7.5 mmol/l), especially when there is a personal or a family history of premature coronary heart disease. [1.1.1]
Healthcare professionals should exclude secondary causes of hypercholesterolaemia before a diagnosis of FH is considered. [1.1.2]
A diagnosis of FH should be made using the Simon Broome criteria, which include a combination of family history, clinical signs (specifically tendon xanthomata), cholesterol concentration and DNA testing (see appendix E NICE guideline or page 7 quick reference guide). [1.1.3]
Healthcare professionals should be aware that the absence of clinical signs (for example, tendon xanthomata) in adults and children/young people does not exclude a diagnosis of FH. [1.1.7]
When considering a diagnosis of FH, healthcare professionals with expertise in FH should use standardised pedigree terminology to document, when possible, at least a three-generation pedigree. This should include relatives’ age of onset of coronary heart disease, lipid concentrations and smoking history. For deceased relatives, the age and cause of death, and smoking history should be documented. If possible, the index individual should verify this information with other family members. [1.1.9]

9. Identifying people with FH using cascade testing
Offer all people with FH a referral to a specialist for confirmation of diagnosis and initiation of cascade testing.
Conduct cascade testing:
using a combination of DNA testing and LDL- C concentration measurement
including at least first-, second- and, when possible, third-degree biological relatives of index individuals.
Nationwide family-based follow-up system is recommended (currently unavailable).
NOTES FOR PRESENTERS:
Recommendations in full:
Healthcare professionals should offer all people with FH a referral to a specialist with expertise in FH for confirmation of diagnosis and initiation of cascade testing (see definitions slide 4) . [1.2.2]
Cascade testing using a combination of DNA testing and LDL-C concentration measurement is recommended to identify affected relatives of those index individuals with a clinical diagnosis of FH. This should include at least the first- and second- and, when possible, third-degree biological relatives. [1.2.4]
The use of a nationwide, family-based, follow-up system is recommended to enable comprehensive identification of people affected by FH. [1.2.8]
Related recommendations:
In families in which a mutation has been identified, the mutation and not LDL-C concentration should be used to identify affected relatives. This should include at least the first- and second- and, when possible, third-degree biological relatives. [1.2.5]
In a family where a DNA mutation is identified, not all family members may have inherited the mutation. When DNA testing has excluded FH in a member of a family, healthcare professionals should manage the person’s coronary heart disease risk as in the general population. [1.1.14]
Key points to raise:
At the present time, no agency is responsible for setting up and running a nationwide family-based follow up system.
Additional information:
NICE have produced an implementation advice tool to support the implementation of the DNA cascade testing recommendations.
NICE have recently produced diagnostics guidance which makes recommendations on different types of genetic tests for the diagnosis of familial hypercholesterolaemia. The recommendations in this guidance support the use of comprehensive genetic analysis (which was the genetic test used in the economic modelling for this guideline) for the confirmation of diagnosis in the index. This diagnostics guidance can be accessed here:

10. Management
Adult:
Consider prescribing a high-intensity statin to achieve a reduction in LDL-C concentration of greater than 50% from baseline.
Children and young people:
Offer referral to a specialist with expertise in FH in children and young people, in an appropriate child/young person-focused setting.
NOTES FOR PRESENTERS:
Recommendations in full:
Adults
Healthcare professionals should consider prescribing a high-intensity statin to achieve a recommended reduction in LDL-C concentration of greater than 50% from baseline (that is, LDL-C concentration before treatment). [ ]
Children and young people
Healthcare professionals should offer all children and young people diagnosed with, or being investigated for, a diagnosis of FH a referral to a specialist with expertise in FH in children and young people. This should be in an appropriate child/young person-focused setting that meets the standards within the ‘National service framework for children, young people and maternity services’ (available from [ ]
Key points to raise:
This chapter in the guideline contains FH management recommendations in the following areas:
Concerning appropriate medical management, increasing dosing of statins, use of Ezetimibe, intolerance of stating and when to refer to a specialist with expertise in FH
Covering referral to a specialist for children and young people diagnosed with and being investigated for FH, the age to initiate lipid modifying therapy, use of statins and other lipid modifying drugs, management of homozygous FH, intolerance of statins and monitoring of growth and pubertal development.
Adults and children/young people
Concerning choice of treatments informed by discussion and consideration of concomitant medication, comorbidities safety and tolerability, offering fat soluble vitamins and folic acid supplements for those receiving resins, referral to specialist if side effects of medical management are experiences and measurement of baseline liver and muscle enzymes for those on statins.
Specialist treatments
Focusing on LDL-lowering apheresis, liver transplantation
Lifestyle interventions
Focusing on diet, physical activity, weight management, alcohol consumption and smoking advice. More details presented on slide 11.

11. Lifestyle advice Diet Physical activity Weight management
Alcohol consumption
Smoking
NOTES FOR PRESENTERS. Lifestyle recommendations (section in the NICE guideline) for people with FH have not been identified as key priorities but have been included here as they are an important component of medical management.
Diet: Offer people with FH individualised nutritional advice from a healthcare professional with specific expertise in nutrition and advise them:
to consume a diet in which; total fat intake is 30% or less of total energy intake, saturated fats are 10% or less of total energy intake, intake of dietary cholesterol is less than 300 mg/day and saturated fats are replaced by increasing the intake of monounsaturated and polyunsaturated fats.
to eat at least five portions of fruit and vegetables a day, in line with national guidance .
to consume at least two portions of fish a week (one of which should be oily fish).
that if they food products containing stanols and sterols these need to be taken consistently to be effective.
Physical activity: Recommended types of physical activity include those that can be incorporated into everyday life, such as brisk walking, using stairs and cycling. Healthcare professionals should advise/encourage people with FH :
to take at least 30 minutes of physical activity a day, of at least moderate intensity, at least 5 days a week, in line with national guidance for the general population.
who are unable to perform moderate-intensity physical activity at least 5 days a week, to exercise at their maximum safe capacity.
that bouts of physical activity of 10 minutes or more accumulated throughout the day are as effective as longer sessions
Weight management: Offer people with FH who are overweight or obese appropriate advice and support to achieve and maintain a healthy weight in line with NICE guidance on obesity
Alcohol consumption: As for the general population, alcohol consumption for adult men with FH should be limited to up to 3–4 units a day, and for adult women with FH up to 2–3 units of alcohol a day
Smoking advice: People with FH, who do not smoke should be strongly discouraged from starting because of their already greatly increased risk of coronary heart disease. Those who do smoke:
advise that, because of their already greatly increased risk of coronary heart disease, they should stop.
and want to stop, offer support, advice and referral, in line with the NICE guidance on smoking cessation
but are unwilling to accept a referral to an intensive support service, offer pharmacotherapy in line with NICE guidance on nicotine replacement therapy and bupropion, and varenicline

12. Information needs and support
For women and girls with FH:
Provide information and counselling on contraception.
Discuss risks for future pregnancy and the fetus while taking lipid-modifying drug therapy at least annually.
NOTES FOR PRESENTERS:
Recommendation in full:
When lipid-modifying drug therapy is first considered for women and girls, the risks for future pregnancy and the fetus while taking lipid-modifying drug therapy should be discussed. This discussion should be revisited at least annually. [ ]
Key points to raise:
The information needs and support chapter of the guideline contains recommendations in the following sections:
General information and support for people with FH. People with FH should:
Receive clear and appropriate educational information about FH, the process of family testing, DNA testing and the measurement of LDL-C concentration.
Receive information on their specific level is risk of coronary heart disease.
Be encouraged to contact their relatives to inform them of their potential risk and offer to facilitate sharing of information about FH with family members.
Information and counseling for women and girls with FH
Give specific information and offer a choice of effective contraceptive methods.
Combined oral contraceptives are not generally contraindicated in this group however, because there is a potential small increased risk of cardiovascular events with the use of combined oral contraceptives healthcare professionals should consider other forms of contraception.
Information for pregnant women with FH
In general, there is no reason to advise against pregnancy or breastfeeding. However, healthcare professionals should advise women:
that lipid modifying drug therapy should be stopped 3 months before conceiving
who conceive while taking lipid modifying drug treatment to stop treatment immediately and should offer urgent referral to an obstetrician
on the potential risks and benefits of re-starting lipid modifying drug therapy for the mother and breastfed infant (Resins should not be considered during lactation)
Shared care arrangements including cardiology and obstetrics should be made for women with FH who are considering or are pregnant.

13. Ongoing assessment and monitoring
Offer all people with FH a regular structured review that is carried out at least annually.
NOTES FOR PRESENTERS:
Recommendation in full:
All people with FH should be offered a regular structured review that is carried out at least annually.
Related recommendations
A baseline electrocardiogram (ECG) should be considered for adults with FH. [ ]
Healthcare professionals should record the progress of cascade testing among the relatives of a person with FH as part of the structured review. This should include at least the first- and second- and, when possible, third-degree biological relatives. If there are still relatives who have not been tested, further action should be discussed. [ ]
Healthcare professionals should update the family pedigree of a person with FH and note any changes in the coronary heart disease status of their relatives as part of the structured review. This should include at least the first- and second- and, when possible, third-degree biological relatives. [ ]
Structured review should include assessment of any symptoms of coronary heart disease and smoking status, a fasting lipid profile, and discussion about concordance with medication, possible side effects of treatment the patient may be experiencing, and any changes in lifestyle or lipid-modifying drug therapy that may be required to achieve the recommended LDL-C concentration (see slide 10). [ ]
Referral for evaluation of coronary heart disease
Healthcare professionals should offer people with FH an urgent referral (definitions slide 4) to a specialist with expertise in cardiology for evaluation if they have symptoms or signs of possible coronary heart disease which are not immediately life-threatening. A low threshold for referral is recommended. [ ]
A person with FH with symptoms or signs of possible coronary heart disease which are immediately life-threatening (for example, acute coronary syndrome) should be referred to hospital as an emergency in line with advice for the general population. [ ]
Healthcare professionals should consider offering people with FH a referral for evaluation of coronary heart disease if they have a family history of coronary heart disease in early adulthood, or two or more other cardiovascular risk factors (for example, they are male, they smoke, or they have hypertension or diabetes). [ ]
Upon diagnosis, healthcare professionals should offer all adults and children/young people with homozygous FH a referral for an evaluation of coronary heart disease. [ ]
In asymptomatic children and young people with heterozygous FH, evaluation of coronary heart disease is unlikely to detect clinically significant disease and referral should not be routinely offered. [ ]

14. Costs and savings for England
Recommendations with significant costs
Costs year 1 (£000)
Costs year 2 (£000)
Costs year 3
(£000)
Cascade testing
4,728
Drug therapy for people identified through cascade testing
2,553
5,106
7,659
Specialist referrals for people identified through cascade testing
693
Annual review meetings
596
1,194
Coronary events avoided
–452
–908
–1,361
Estimated cost of implementation
7,522
10,216
12,913
ADAPTING THIS SLIDE FOR LOCAL USE:
We are aware that local factors such as incidence and baseline can vary considerably when compared with the national average. NICE has provided a costing template for you to calculate the financial impact this guideline will have locally. We encourage you to calculate the local impact of this guideline by amending the local variations in the template such as incidence, baseline and uptake. You can then remove the national figures from the table and replace them with your local figures to present to your colleagues.
NOTES FOR PRESENTERS:
The information on this slide has been extracted from the NICE costing report, which has been provided by NICE to support implementation of this guidance on FH. It was developed after careful consideration of the available data and by working closely with the guideline developers and other people in the NHS. It is not NICE guidance. Assumptions used in this report are based on assessment of the national average and it is recognised that local practice or circumstances may differ from this. The costs published in this report are estimates only and are not to be taken as NICE's view of desirable, or maximum or minimum figures.
NICE has also provided a costing template to help calculate the local costs associated with implementing this guideline. The costs for England are summarised in the table. The expected cost of implementation for a local population of 100,000 in the first year is £15,000.
It is recognised that implementation of the recommendations may take place over a number of years. Cascade testing of existing index individuals is expected to take 5–10 years, and the costs and savings for the first 3 years of implementation are shown in the table.
Identifying people with FH through cascade testing and treating them appropriately will lead to a reduction in coronary events for these people. In England, the implementation of this guideline is expected to avoid 400 coronary events in people with currently undiagnosed FH in the first 3 years of implementation.
In addition, compliance with NICE guidance is one of the criteria indicating good risk reduction strategies, and in combination with meeting other criteria could lead to a discount on contributions to the NHS Litigation Authority schemes, including the clinical negligence scheme for trusts (CNST).
For further information please refer to the costing template and costing report for this guidance on the NICE website.
Costs correct at Aug
Costs not updated for 2nd edition

15. For discussion
What do we need to do to ensure efficient identification of people with FH?
What is our local care pathway for FH?
How will we involve commissioners to develop the cascade testing service?
How are children with FH managed locally?
What information and advice do we have to share with people with FH?
NOTES FOR PRESENTERS:
These questions are suggestions that have been developed to help provide a prompt for a discussion at the end of your presentation – please edit and adapt these to suit your local situation.
Additional information:
Resources for patients
The guideline recommends referring people with FH to for further practical advice about healthy diets and alcohol consumption

16. Click here to go to NICE Pathways website
Our new online tool provides quick and easy access, topic by topic, to the range of guidance from NICE
NOTES FOR PRESENTERS:
NICE Pathways: guidance at your fingertips
Our new online tool provides quick and easy access, topic by topic, to the range of guidance from NICE, including quality standards, technology appraisals, clinical and public health guidance and NICE implementation tools. Simple to navigate, NICE Pathways allows you to explore in increasing detail NICE recommendations and advice, giving you confidence that you are up to date with everything we have recommended.
Click here to go to NICE Pathways website

17. Click here to go to the NHS Evidence website
Visit NHS Evidence for the best available evidence on all aspects of Familial Hypercholesterolaemia.
Click here to go to the NHS Evidence website
NOTES FOR PRESENTERS:
If you are showing this presentation when connected to the internet, click on the blue button to go straight to the NHS Evidence website.
The home page is

18. Find out more Visit www.nice.org.uk/guidane/CG071 for:
Other guideline formats
Costing report and template
Audit support, including electronic audit tool
Implementation advice
NOTES FOR PRESENTERS:
The guideline is available in a number of formats.
The quick reference guide – which summarises the guidance.
The NICE guideline – which includes all of the recommendations in full.
The full guideline – which includes all of the evidence and rationale.
‘Understanding NICE guidance’ – a version for patients and carers.
You can download these from the NICE website.
NICE has developed tools to help organisations implement this guideline, which can be found on the NICE website.
Costing tools – a costing report gives the background to the national savings and costs associated with implementation, and a costing template allows you to estimate the local costs and savings involved.
Audit support, including an electronic audit tool – assists NHS trusts to determine how well they meet NICE recommendations.
Implementation advice – provides information and advice to help support those responsible for implementing the genetic testing for FH recommendations in practice.
Related NICE guidance:
Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease' (NICE clinical guideline 67).
Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolaemia (NICE diagnostics guidance 2)
Slide 11 refers specifically to the following pieces of NICE guidance:
Obesity: guidance on the prevention, identification, assessment and management of overweight and obesity in adults and children (NICE clinical guideline 43).
Brief interventions and referral for smoking cessation in primary care and other settings (NICE public health intervention guidance 1).
Guidance on the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation (NICE technology appraisal guidance 39).
Varenicline for smoking cessation (NICE technology appraisal guidance 123).
Visit for
the NICE diagnostic guidance on types of genetic tests for confirming a diagnosis of FH

19. What do you think?
Did the implementation tool you accessed today meet your requirements, and will it help you to put the NICE guidance into practice?
We value your opinion and are looking for ways to improve our tools. Please complete this short evaluation form.
If you are experiencing problems accessing or using this tool, please
NOTES FOR PRESENTERS:
Additional information:
The final slide is not intended to be part of the presentation, it asks for feedback on whether this implementation tool meets your requirements and whether it will help you to put this NICE guidance into practice - your opinion would be appreciated.
To open the links in this slide set right click over the link and choose ‘open link’
To open the links in this slide set right click over the link and choose ‘open link’