Article Archive

PCSK9 and plaque: trials

Recent trials have shown that the PCSK9 monoclonal antibodies lower LDL cholesterol by more than 50% on top of statin therapy. There is also evidence that serum PCSK9 is associated with carotid intima-media thickness, a surrogate for atherosclerosis. Lee CJ, Lee YH, Park SW et…

Professor Gerald Watts discusses the 10 countries project in FH

The International Atherosclerosis Society has begun a study in Asia and the Pacific Rim to provide the first comprehensive investigation of the worlds commonest genetic disorder, familial hypercholesterolaemia (FH) in the region. FH results in very high levels of low density lipoprotein cholesterol (LDL-C) and…

Rising to the Challenge: Implementing Models of Care in FH

Winthrop Professor Gerald F. Watts DSc PhD MD FRACP FRCP, Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital School of Medicine and Pharmacology, University of Western Australia. GPO Box X2213, Perth, WA 6847, Australia; E-mail: [email protected] While several guidelines, mostly based on expert opinion, have…

PCSK9: Opportunities for personalised medicine?

Personalised medicine shifts the focus from a ‘one-size-fits-all’ to patient-centred alternatives. This undoubtedly benefits both patients and healthcare budgets. Such an approach has already been integrated into other disciplines, such as oncology. Is such a strategy also relevant in the management of familial hypercholesterolaemia (FH)?…

What are the current unmet needs?

Despite statins, there are significantly unmet clinical needs in cholesterol lowering treatment. Statin do not effectively treat more than 50% of people with Familial Hypercholesterolaemia (FH) and other patients have intolerable side effects, says Professor Erik Stroes.

Statins and plaque burden

The clinical benefit of LDL cholesterol lowering with statins has been conclusively demonstrated with a wealth of experience from primary and secondary prevention clinical trials.1,2 In addition, imaging studies have shown that statins have a favourable effect on atherosclerosis progression, either stabilising or even decreasing…

Unmet needs in children with FH

Identification and treatment to reduce low density lipoprotein cholesterol (LDL-C) of children with familial hypercholesterolaemia (FH) is vital to reduce the risk of cardiovascular death in early adulthood. FH is the most common genetic disorder in the world. Parents and healthcare professionals need to be…

Improving the management of the FH patient

Professor Raul Santos from Brazil says that the new therapies which inhibit PCSK9 to significantly reduce low density Lipoprotein Cholesterol (LDL-C) when given in addition to other cholesterol lowering drugs offer a very important advance in reducing cardiovascular risk in people with Familial Hypercholesterolemia (FH).

Do the PCSK9 monoclonal antibodies have neurocognitive adverse effects?

Evolocumab

ACC 2014 March 29th  MENDEL-2: http://www.pcsk9forum.org/mendel-2-2/ DESCARTES: http://www.pcsk9forum.org/descartes-durable-ldl-c-lowering-with-evolocumab/ RUTHERFORD-2: http://www.pcsk9forum.org/acc-2014-rutherford-2-evolocumab-in-heterozygous-fh/ LAPLACE-2: http://www.pcsk9forum.org/acc-2014-latebreaker-laplace-2-evolocumb-effective-in-patients-on-high-and-moderate-intensity-statins/ GAUSS-2: http://www.pcsk9forum.org/acc-2014-latebreaker-gauss-2-evolocumab-addresses-unmet-needs-in-statin-intolerance/  

Lipoprotein apheresis lowers plasma PCSK9

Lipoprotein apheresis is clearly important in the management of severe familial hyperchoelsterolaemia (FH). However, its use is not without practical and cost limitations. Evidence that lipoprotein apheresis has an additional benefit in lowering plasma PCSK9 levels, beyond effects on low-density lipoprotein cholesterol (LDL-C), suggests that…

PCSK9: From discovery to therapeutic applications

PUBMED abstract: http://www.ncbi.nlm.nih.gov/pubmed/24373748

TESLA in brief

TESLA was a randomised, double-blind, placebo-controlled trial of the PCSK9 inhibitor, evolocumab, in 50 patients (49 received treatment) with homozygous FH (mean LDL-C at baseline 9.0 mmol/L). All were on statins and 91% also received ezetimibe. LDL receptor mutations were identified in 45 (92%) patients;…

Mechanistic insights from PCSK9 LOF mutations

Mechanistic insights from PCSK9 LOF mutations with a particular focus on data from the Copenhagen studies, were discussed by Professor Anne Tybjaerg-Hansen, Rigshospitalet, Copenhagen University Hospital, and University of Copenhagen, Denmark. Seminal studies showed that carriage of LOF mutations was associated reduction in LDL cholesterol…

How low should LDL cholesterol be lowered – and for how long?

RUTHERFORD-2 in brief

RUTHERFORD-2 was a large, randomised, placebo-controlled trial of the PCSK9 inhibitor, evolocumab, in 331 patients with heterozygous familial hypercholesterolaemia (mean LDL-C at baseline 3.9-4.2 mmol/L). All were on statins and 62% were also on ezetimibe. FH-causing mutations were identified in 80% of patients, most were…

Missing FH: How can we improve FH referral and diagnosis?

Heterozygous familial hypercholesterolemia (FH) is neither a rare disease nor a sentence to a life full of complications and early death. Recent evidence shows that even when founder effects are taken into account, heterozygous FH affects around 1/200-300 people instead of the historical estimate of…

Will the PCSK9 monoclonal antibodies replace other lipid lowering treatments currently used with statins?

Where will the new PCSK9 inhibitors fit into the treatment of people whose raised low density lipoprotein cholesterol (LDL-C) puts them at high risk of cardiovascular disease? Leading researcher, Professor Frederick Raal discusses this important question.

In your opinion, what are the optimum patient populations for PCSK9 monoclonal antibody therapy?

PCSK9 monoclonal antibodies offer very important new treatments to lowed low density lipoprotein cholesterol (LDL-C) in patients who cannot tolerate statins or whose LDL-C is inadequately reduced as well as those people with high LDL-C caused by Familial Hypercholesterolemia.

PCSK9 inhibitors and FH: future for standard of care?

Two recent trials in FH patients – RUTHERFORD-2 and TESLA – have raised the focus of the PCSK9 inhibitors in FH.  In an accompanying Lancet editorial, Profs. Raul Santos (Sao Paulo, Brazil) and Gerald Watts (Perth, Australia) have intimidated that PCSK9 inhibitors might represent the…