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Dyslipidaemia - management in LEAP follow up

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Because metabolic syndrome is known to have increased incidence in survivors of treatment for childhood cancer and because it is recognized to occur at an earlier age than in the general population, screening for physical and biochemical evidence of its early signs has become common practice in follow-up clinics.

There is good evidence for the practices of discouraging smoking and for screening for hypertension and treating it in this population in order to prevent later cardiovascular disease. However, advice on universal screening and drug treatment for dyslipidaemia in children and adolescents is controversial and this guideline is developed in order to provide consistency of approach for LEAP follow-up.

The following points are relevant:

  • A high level of low density lipoprotein is a cause of atherosclerosis and related clinical events

  • Health benefits of statins in adults are well established (30% reduction in coronary events and 12% reduction in total mortality) so that recent guidelines have expanded recommendations for more aggressive statin prescription and extension to intermediate risk groups

  • Large long term trials have failed to show similar benefits for other therapies for dyslipidaemia (Clofibrate, Ezetimibe, Fenofibrate) so the indication for these agents is less certain. The recent IMPROVE-IT study showed a modest benefit of adding ezetimibe to statin therapy in patients with established cardiovascular disease but there are no data for its use in prevention (That is, the population this guidance is designed for

  • Statins are associated with significant side effects, particularly serious myopathy and rhabdomyolysis, but more often, aches and pains in the large joints

  • There are concerns around the use of drug induced lowering of lipid levels to infer health benefits (reduced risk of atherosclerosis, clinical cardiovascular disease and reduced mortality)

  • There is little evidence that long term drug treatment to lower lipids in young children is effective and safe

  • Apart from the additional risk factor of previous treatment for childhood cancer, there may be familial risk factors which should be explored

  • In NZ BPAC guidance is based on 5 year CVD risk and it is unclear whether the younger age group which is being managed in LEAP clinics was included in assembling this data

  • Hypertriglyceridemia is usually secondary to a condition such as abdominal obesity, excessive alcohol intake or poorly controlled diabetes, perhaps interacting with underlying genetic Familial Combined Hyperlipidaemia. It responds best to treatment of the underlying cause

  • Treatment of hypertriglyceridemia is appropriate when there is a risk of acute pancreatitis- the usual conservative threshold for treatment being a fasting triglyceride of 5-6 mmol/L

  • A prolonged fast may be necessary to truly establish a significantly raised triglyceride level before considering a fibrate or a statin alone if there is combined dyslipidaemia

  • Currently, pharmacological treatment of hyperlipidaemia in Australasian children and young people appears to be largely confined to those with Familial Hypercholesterolaemia when there is a strong family history of premature cardiovascular disease

  • Patients who have had irradiation to the chest with or without anthracycline chemotherapy are at a particularly elevated risk for premature cardiovascular disease if they also have hyperlipidaemia

  • Intensive lifestyle management does not have the potential side effects of pharmacological agents

The following actions are therefore recommended:

  • Strong advice to refrain from beginning smoking or assistance in quitting

  • Strong advice to control unhealthy weight gain

  • Advice to have BP checked and managed if persistently high (including screening for underlying cause, lifestyle and weight control measures and anti-hypertensive medication where appropriate)

  • Strong advice on healthy lifestyle including regular exercise and sensible eating practices

  • Advice to attend regular medical review (annual family doctor check)

  • Prescription of statins such as simvastatin or atorvastatin only when fasting testing has confirmed significant elevation of cholesterol, low HDL-C, elevation of cholesterol/HDL ratio and dietary modification, increased exercise and weight loss has proved ineffective in older AYA patients and an informed choice is made taking into account the lack of long term safety data and risk of muscle and joint pain and rhabdomyolysis. Patients who will have most benefit from this strategy are those with additional risk factors such as chest irradiation or family history of hyperlipidaemia and early cardiovascular disease as their risk reduction may justify the burden of treatment

  • Prescription of triglyceride lowering agents such as benzafibrate only when fasting testing has confirmed very significant elevation of triglyceride to 5-6 mmol/L with associated risk for pancreatitis, and dietary control and alcohol reduction has been ineffective

  • The considered view of this panel is that cardiovascular risk is likely to be low in the majority of these young people and lifestyle management of elevated lipids should be the mainstay of management. Pharmacological management may be indicated in selected patients with very high risk and should be undertaken in association with a physician with an interest in this patient group. These patients will include those with persistently significantly elevated lipids despite intensive lifestyle management who also have a strong family history of early familial cardiac morbidity/ mortality, a family history of dyslipidaemia or a history of thoracic radiation therapy


References

  1. Metabolic Syndrome in adult survivors of childhood cancer: the intersection of oncology, endocrinology and cardiology. Matthew J. Ehrhardt, Daniel A.Mulrooney. Lancet Vol3,no 7, p494-496, July 2015.

  2. Long-term survivors of childhood cancer have an increased risk of manifesting the metabolic syndrome. KK Tavensaari, M Lanning, P Tapanainen and M Knip. The Journal of Clinical Endocrinology and Metabolism Vol 81, issue 8 April 2011

  3. Metabolic Syndrome and Growth Hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. James Gurney etal. Cancer Sept 15, 2006. Vol 107, No 6, 1303-12

  4. Chronic health conditions in adult survivors of childhood cancer. Kevin Oeffinger etal. NEJM 2006;355:1572-82

  5. Universal Screening and drug treatment of Dyslipidemia in children and adolescents. Bruce M. Psaty, Frederick P. Rivara. JAMA;2012;307(3):257-258

  6. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary report. Pediatrics.2011;128:(suppl 5)

  7. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors; meta-analysis of randomized controlled trials. Brugts JJ,Yetgin T, Hoeks SE, et al. BMJ.2009;338:b2376

  8. An Update on Statins; BPAC NZ Best practice Journal 2010, BPJ30

  9. Paediatric Dyslipidemia: Recommendations for Clinical Management. Don P. Wilson, Catherine McNeal, Piers Blackett South Med J 2015;108(1):7-14US Preventive Services Task Force. Screening for lipid disorders in children and adolescents. JAMA 2016; 316:625-633.

  10. US Preventive Services Task Force. Screening for lipid disorders in children and adolescents. JAMA 2016; 316:625-633. Article

  11. Lozano P, Henrikson NB, Morrison CC, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia. JAMA 2016; 316:634-644. Article

  12. Lozano P, Henrikson NB, Dunn J, et al. Lipid screening in childhood and adolescence for detection of familial hypercholesterolemia. JAMA 2016; 316:645-655. Article

  13. Samuel S. Gidding. Why cholesterol testing in children and adolescents matters. JAMA Cardiol 2016; Article

  14. Newman TB, Schroeder AR, Pletcher MJ. Lipid screening in children. JAMA Intern Med 2016; DOI:10.1001/jamainternmed.2016.5114. Article

  15. Daniels SR. On the US Preventive Services Task Force Statement on Screening for lipid disorders in children and adolescents. JAMA Pediatrics 2016; Article

  16. Urbina EM, de Ferranti SD. Lipid screening in children and adolescents. JAMA 2016; 316:589-591. Article

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Document Control

  • Date last published: 15 August 2016
  • Document type: Clinical Guideline
  • Services responsible: National Child Cancer Network
  • Author(s): Scott Macfarlane, Ruellyn Cockcroft, Jane Skeen, Kathy Yallop, Rob Corbett, Rick Cutfield, Jocelyne Benatar, Ross Boswell, Leah Ha
  • Owner: Scott Macfarlane
  • Review frequency: 3 years

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