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Page M.M.,Lipid Disorders Clinic | Watts G.F.,Lipid Disorders Clinic | Watts G.F.,University of Western Australia
Expert Opinion on Emerging Drugs | Year: 2015

Introduction: Atherosclerotic cardiovascular disease (ACVD) is the leading cause of mortality worldwide. An abnormally high plasma level of low-density lipoprotein-cholesterol is a major contributor to ACVD, an effect that can be attenuated by cholesterol-lowering therapies, particularly statins. A new class of drugs, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, will add another option for further reducing cardiovascular events in patients at high risk of ACVD, including those with familial hypercholesterolaemia (FH) and intolerance to statins. Patients with elevated levels of lipoprotein(a) (Lp(a)) are difficult to treat with conventional therapies, and may also benefit from PCSK9 inhibitors.Areas covered: This paper discusses the medical need for additional cholesterol-lowering therapies and the scientific rationale and current therapeutic status of PCSK9 inhibitors.Expert opinion: The use of anti-PCSK9 mAbs is the leading form of therapy for inhibiting PCSK9 and is likely to provide genuine hope for patients with FH, statin intolerance and elevated Lp(a) their ability to reduce cardiovascular events in patients maximally treated with statins and other existing therapies remains to be proven, and is the subject of major ongoing clinical trials. © 2015 Informa UK, Ltd.

Watts G.F.,Lipid Disorders Clinic | Juniper A.,Lipid Disorders Clinic | van Bockxmeer F.,Cardiovascular Genetics Laboratory | Ademi Z.,Royal Melbourne Hospital | And 3 more authors.
International Journal of Evidence-Based Healthcare | Year: 2012

Familial hypercholesterolaemia (FH) is a condition that should be familiar to all health professionals involved in preventive medicine. FH is the most common and serious monogenic disorder of lipid metabolism that leads to premature coronary heart disease. However, most cases remain undetected or inadequately treated in our community. We provide an overview of FH, with emphasis on evidence for treatment, new models of care (MoCs) and health economic evaluations. Evidence for treatment is based on cohort studies; while this is a low level class of evidence, MoCs concur in recommending early intervention and lowering of plasma low-density lipoprotein-cholesterol levels by at least 40% with statins. Preliminary health economic evaluations suggest that detecting and treating FH is cost-effective, but further studies based on high-quality international data and standardised costing methods are needed. If the recommendations in the published MoCs are followed, there is likely to be significant improvement in the health and quality of life of patients with FH and their families, as well as major cost savings in healthcare for end-organ damage, including myocardial infarction, acute coronary syndromes and possibly stroke, but this requires to be verified. © 2012 The Authors International Journal of Evidence-Based Healthcare. © 2012 The Joanna Briggs Institute.

Page M.M.,Lipid Disorders Clinic | Stefanutti C.,University of Rome La Sapienza | Sniderman A.,McGill University | Watts G.F.,Lipid Disorders Clinic | Watts G.F.,University of Western Australia
Clinical Science | Year: 2015

Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder that markedly raises plasma low-density lipoprotein-cholesterol (LDL-C) concentration, causing premature atherosclerotic coronary artery disease (CAD). FH has recently come under intense focus and, although there is general consensus in recent international guidelines regarding diagnosis and treatment, there is debate about the value of genetic studies. Genetic testing can be cost-effective as part of cascade screening in dedicated centres, but the full mutation spectrum responsible for FH has not been established in many populations, and its use in primary care is not at present logistically feasible. Whether using genetic testing or not, cholesterol screening of family members of index patients with an abnormally raised LDL-C must be used to determine the need for early treatment to prevent the development of CAD. The metabolic defects in FH extend beyond LDL, and may affect triacylglycerol-rich and high-density lipoproteins, lipoprotein(a) and oxidative stress. Achievement of the recommended targets for LDL-C with current treatments is difficult, but this may be resolved by new drug therapies. Lipoprotein apheresis remains an effective treatment for severe FH and, although expensive, it costs less than the two recently introduced orphan drugs (lomitapide and mipomersen) for homozygous FH. Recent advances in understanding of the biology of proprotein convertase subtilisin/kexin type 9 (PCSK9) have further elucidated the regulation of lipoprotein metabolism and led to new drugs for effectively treating hypercholesterolaemia in FH and related conditions, as well as for treating many patients with statin intolerance. The mechanisms of action of PCSK9 inhibitors on lipoprotein metabolism and atherosclerosis, as well as their impact on cardiovascular outcomes and cost-effectiveness, remain to be established. © The Authors Journal compilation © 2015 Biochemical Society.

Foley D.L.,University of Melbourne | MacKinnon A.,University of Melbourne | Morgan V.A.,University of Western Australia | Watts G.F.,Lipid Disorders Clinic | And 6 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2015

Objective: Antipsychotic drug treatment alters status on key risk factors for cardiovascular disease. The aim of this study was to test whether cardiovascular risk factor associations differ in adults with psychosis and adults from the general community. Method: Data were analysed for those aged 25-64 years from a nationally representative psychosis sample (n = 1,457) and a national comparator sample (n = 8,866). The Pearson correlation coefficient was used to estimate the association among tobacco use, body mass index, waist circumference, diastolic and systolic blood pressure and fasting total-, LDL-and HDL-cholesterol, triglycerides and plasma glucose. The robust Levene test was used to test for sample differences in variance. Results: Correlations among cardiovascular risk indicators and between cardiovascular risk indicators and age were often significantly weaker in those with psychosis than in those from the national comparator sample. This was not due to a reduction in variance within the psychosis sample. Conclusions: Risk prediction that synthesizes multivariate risk indicator data needs to be connected to verified cardiovascular morbidity and mortality in those with psychosis to determine if standard risk calculators adequately discriminate those at high, medium and low future risk of cardiovascular morbidity and mortality. Until then the clinical implications of low or absent correlations among cardiovascular risk indicators and their low or absent association with increasing age is unclear but may indicate that risk equations commonly used in the general population may not be applicable for those with treated psychosis. © 2015 The Royal Australian and New Zealand College of Psychiatrists.

Bell D.A.,Lipid Disorders Clinic | Bell D.A.,University of Western Australia | Garton-Smith J.,A+ Network | Vickery A.,University of Western Australia | And 6 more authors.
Heart Lung and Circulation | Year: 2014

Aim: To determine general practitioners' (GPs') knowledge and practice regarding familial hypercholesterolaemia (FH) in Western Australia. Method: A structured questionnaire was anonymously completed by GPs. Information was sought on awareness and knowledge of FH including, diagnosis, inheritance, prevalence, cardiovascular risk, management practices and opinions on FH screening. Results: 191 GPs completed the survey, 62% were familiar with FH, 80% correctly defined FH and 68% identified the typical lipid profile, but only 33% were aware of national guidelines. There were knowledge deficits in prevalence, inheritance, and clinical features of FH, with correct responses in 27%, 45% and 38%, respectively. Most (84%) GPs considered themselves the most effective health professionals to detect FH, with 90% preferring laboratory interpretative commenting to highlight individuals at risk of FH. GPs identified appropriate cholesterol lowering drugs as mono (95%) or combination therapies (74%). Conclusion: The majority of GPs considered they were the most effective health practitioners for managing FH and preferred laboratory reports to alert them of possible FH. Although GPs knowledge of cholesterol lowering therapies was good, their awareness of national guidelines, hereditability, prevalence and diagnostic features of FH was suboptimal. Implementing a community model of care for FH requires more extensive GP education. © 2013.

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