key: cord-0785765-c46b3dk4 authors: Watts, Gerald F.; Sullivan, David R.; Hare, David L.; Kostner, Karam M.; Horton, Ari E.; Bell, Damon A.; Brett, Tom; Trent, Ronald J.; Poplawski, Nicola K.; Martin, Andrew C.; Srinivasan, Shubha; Justo, Robert N.; Chow, Clara K.; Pang, Jing title: Synopsis of an integrated guidance for enhancing the care of familial hypercholesterolaemia: an Australian perspective date: 2021-02-04 journal: Am J Prev Cardiol DOI: 10.1016/j.ajpc.2021.100151 sha: 2b85dc412dd7aca065221d44bd6e02807f05cb88 doc_id: 785765 cord_uid: c46b3dk4 INTRODUCTION: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH. MAIN RECOMMENDATIONS: Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. There is a key role for general practitioners (GPs) working in collaboration with specialists with expertise in lipidology. Advice is given on genetic and cholesterol testing and risk notification of biological relatives undergoing cascade testing for FH; all healthcare professionals should develop skills in genomic medicine. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors, and appropriate use of low-density lipoprotein (LDL)-cholesterol lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recommendations on service design are provided in the full guidance. POTENTIAL IMPACT ON CARE OF FH: These recommendations need to be utilised using judicious clinical judgement and shared decision making with patients and families. Models of care need to be adapted to both local and regional needs and resources. In Australia new government funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of these recommendations. A broad implementation science strategy is, however, required to ensure that the guidance translates into benefit for all families with FH. Familial hypercholesterolaemia (FH) is a common and severe cause of premature coronary atherosclerosis due to variants in genes affecting the clearance of low-density lipoprotein (LDL)-cholesterol. FH is a preventable cause of premature disease and death, with significant potential for positive impact on public health and healthcare savings [ 1 , 2 ] . However, less than 10% of people with FH have been identified and, of those treated, over 80% do not attain LDL-cholesterol targets [2] . The FH Australasia Network Consensus Group has developed a new guidance to assist clinicians in the care of patients with FH, replacing earlier recommendations [3] . This synopsis provides the key recommendations as actionable statements with their strength of evidence. The full guidance, endorsed by several organisations (see appendix), is available in Heart, Lung and Circulation at https://doi.org/10.1016/ j.hlc.2020.09.943 [4] . A steering committee, selected from board members of the FH Australasia Registry Network [5] , appointed a writing group and invited contributions from diverse clinical specialties and health consumers [4] . The protocols followed are detailed elsewhere [4] . Evaluation of the published evidence on the care of FH was based on the GRADE system [ 4 , 6 ] . The totality of evidence, including expert opinion and patient preferences, informed the recommendations. Recommendations are presented with a class of recommendation (CoR) and level of evidence (LoE). Additional recommendations, including lipoprotein apheresis and organisation of care, are given in the full guidance [4] . Conversion factors in the recommendations are: for cholesterol, from mmol/L to mg/dL multiply mmol/L by 38.67; for triglycerides, from mmol/L to mg/dL multiply mmol/L by 88.57. ( Table 1 ) and genetic criteria, but when genetic testing is not available the diagnosis should be made phenotypically [ 3 , 7 ] Table 1 The Dutch Lipid Clinic Network criteria for making the phenotypic diagnosis of familial hypercholesterolaemia in adult index cases [1] [2] [3] . For online use, please access the FH Australasia Network calculator at https://www.athero.org.au/fh/calculator/ . These criteria should not be used to diagnose FH in children or adolescents [10] . Criteria * Score Section 1: Family history First degree relative with known premature coronary and/or vascular disease (men aged < 55 years, women aged < 60 years) OR First degree relative with known LDL-cholesterol above the 95th percentile for age and gender 1 First degree relative with tendinous xanthomata and/or arcus cornealis OR Children aged < 18 years with LDL-cholesterol above the 95th percentile for age and gender 2 Section 2: Personal history Patients with premature coronary artery disease (men aged < 55 years, women aged < 60 years) 2 Patients with premature cerebral or peripheral vascular disease (men aged < 55 years, women aged < 60 years) 1 Section 3: Physical examination Tendinous xanthomata 6 Arcus cornealis before 45 years of age 4 Section 3: Biochemical results: to convert cholesterol to mg/dL multiply mmol/L below by 38.67 [3] . ˆConsistent with relevant local legislation and institutional guidelines * According to age-and gender-specific plasma LDL-cholesterol concentrations published by Starr et al. [31] . Age-dependent LDL-cholesterol concentrations and thresholds (mmol/L; to convert to mg/dL multiply mmol/L by 38.67) to make a diagnosis of FH during cascade testing in (a) male and (b) female first-degree relatives of an index case. Adapted from Starr et al. [31] . 8. Genetic cascade testing should initially be prioritised for first-degree relatives of a variant carrier and sequentially extended as additional carriers are identified; if first-degree relatives decline testing, testing should be extended to second-degree followed by third-degree relatives (also applies to phenotypic testing alone) ( Fig. 1 ) [ 17 , 36 , 38 ] , which may include children and adolescents. LDL-cholesterol targets are based on primary or secondary prevention settings [ 1 , 4 ] ; patients should be on at least 3 months of therapy and above the targets before proceeding to next step. * For targets, see Management of Adults in text. Adapted from Pang et al. 2020 [2] . 13. In women with homozygous FH and clinical ASCVD, use of statins and ezetimibe may be considered after the first trimester [ 1 , 5 , 36 ] This guidance is aligned with a recent international call to action on FH [50] . The recommendations need incorporation into healthcare pathways that meet the needs of the population [ 1 , 2 ] . In Australia, government funded schemes that support appropriate genetic testing and use of PCSK9 monoclonal antibodies will contribute significantly to enhancing the care of patients with FH [ 2 ] . The critical barrier that needs to be overcome is translating our guidance into health policy and high-quality care. Implementation research and practice [ 51 , 52 ] must be embraced as a national health priority to increase the impact of the guidance on improving the care of all people with or at risk of FH. This challenge and recommendation applies globally to all countries aiming to close major gaps in the care of FH [51] . The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Disclosures GFW has received honoraria for advisory boards and research grants from Amgen, Arrowhead, Gemphire, Kowa, Novartis, Pfizer, Sanofi and Regeneron. DRS has received grants from Regeneron, Amgen, As-traZeneca, Amarin, Espirion, and Novartis, as well as personal fees from Amgen and Sanofi. DLH has received consulting fees, educational grants, research grants or advisory board honoraria from Amgen, Astra-Zeneca, Boehringer-Ingelheim, Menarini, MSD, Novartis, Pfizer, Sanofi-Regeneron, Servier and Vifor. DAB has received honoraria from Amgen, Nestle and Sanofi. TB has received grants and honoraria from Amgen and Sanofi. CKC has participated either as a participant or speaker in educational meetings sponsored by pharmaceutical companies that make lipid-lowering therapies. KMK, RJT, ACM, SS, RNJ, NKP, AEH and JP have no disclosures. No funding from the pharmaceutical industry or other industry groups was obtained to support the development of this guidance on FH. JP was supported by a WAHTN Early Career Fellowship and the Australian Government's Medical Research Future Fund. ) Gemma A Figtree (Kolling Institute, Royal North Shore Hospital, Sydney School of Medicine, Faculty of Health and Medical Sciences Jodie Ingles (Agnes Ginges Centre for Molecular Cardiology at Centenary Institute Western Health Chronic Disease Alliance, Western Health Public Health Genomics, School of Public Health and Preventive Medicine Western Australia, Australia; Department of Cardiovascular Medicine Wesley Hospital and Greenslopes Private Hospital Australia Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care Familial hypercholesterolaemia in 2020: a leading tier 1 genomic application Familial hypercholesterolaemia: a model of care for Australasia Integrated guidance for enhancing the care of familial hypercholesterolaemia in Australia Gaps in the care of familial hypercholesterolaemia in Australia: first report from the national registry GRADE: an emerging consensus on rating quality of evidence and strength of recommendations The agenda for familial hypercholesterolemia -a scientific statement from the American heart association Screening for familial hypercholesterolaemia in primary care: time for general practice to play its part Child-parent familial hypercholesterolemia screening in primary care Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the task force for the management of dyslipidaemias of the European society of cardiology (ESC) and European atherosclerosis society (EAS) Clinical genetic testing for familial hypercholesterolemia: JACC scientific expert panel Predicting cardiovascular events in familial hypercholesterolemia: the SAFE-HEART registry Use of Lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the national lipid association Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study Coronary artery calcium and cardiovascular events in patients with familial hypercholesterolemia receiving standard lipid-lowering therapy HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom Current management of children and young people with heterozygous familial hypercholesterolaemia -HEART UK statement of care Parent-child genetic testing for familial hypercholesterolaemia in an Australian context Universal screening for familial hypercholesterolemia in children Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American heart association 20-year follow-up of statins in children with familial hypercholesterolaemia Practice of lipoprotein apheresis and short-term efficacy in children with homozygous familial hypercholesterolemia: data from an international registry The present and the future of genetic testing in familial hypercholesterolemia: opportunities and caveats Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology HGVS recommendations for the description of sequence variants: 2016 update 1534 -heritable mutations associated with familial hypercholesterolaemia -clinical utility card application Commonwealth of Australia as represented by the department of health. National health genomics policy framework and implementation The Royal Australian College of General Practitioners Genomics in general practice Cascade screening based on genetic testing is cost-effective: evidence for the implementation of models of care for familial hypercholesterolaemia Development of sensitive and specific age-and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing PCNA guideline on the management of blood cholesterol. A report of the American college of cardiology ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines Enablers and barriers to treatment adherence in heterozygous familial hypercholesterolaemia: a qualitative evidence synthesis Survival in homozygous familial hypercholesterolaemia is determined by the on-treatment level of serum cholesterol Familial hypercholesterolemia treatments: guidelines and new therapies Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis Toward an international consensus -integrating lipoprotein apheresis and new lipid-lowering drugs Practical guidelines for food consumption to prevent cardiovascular disease Evolocumab and clinical outcomes in patients with cardiovascular disease Alirocumab and cardiovascular outcomes after acute coronary syndrome Optimizing cholesterol treatment in patients with muscle complaints National lipid association scientific statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland Impact of statins on serial coronary calcification during atheroma progression and regression Efficacy of rosuvastatin in children with homozygous familial hypercholesterolemia and association with underlying genetic mutations Known and unknowns in the care of paediatric familial hypercholesterolaemia Carotid intima-media thickness in children with familial hypercholesterolemia Representatives of the global familial hypercholesterolemia community. Reducing the clinical and public health burden of familial hypercholesterolemia -a global call to action The time has come: embedded implementation research for health care improvement Developing implementation strategies to improve uptake of guideline-recommended treatments for individuals with familial hypercholesterolemia: a protocol