News

Overlap between HoFH and severe FH and implications for evolocumab

The implications of the overlap between homozygous hypercholesterolaemia and severe familial hypercholesterolaemia (FH) – two genetic disorders characterised by very high levels of low density lipoprotein cholesterol (LDL-C) – should be considered when selecting treatment. Professor Frederick Raal discusses the issue.

ACC 2014 Latebreaker: LAPLACE-2: Evolocumab effective in patients on high and moderate-intensity statins

The recent ACC/AHA guidelines have focused on the intensity of statin therapy for lowering LDL-C.  Consequently, the LAPLACE-2 (Low-density Lipoprotein Cholesterol Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy – 2) phase III trial assessed the efficacy of evolocumab in patients with hypercholesterolaemia…

Canadian perspective on the 2013 ACC-AHA guidelines on the treatment of blood cholesterol

Professor Robert A. Hegele Western University, London, ON Canada N6A 5B7 email: [email protected] Shortly after publication of the 2013 American College of Cardiology and American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol (1), the authors of the 2012 Canadian Cardiovascular Society (CCS)…

Implications from TESLA for FH management

ACC 2014 MENDEL-2: More evidence for evolocumab monotherapy in treatment-naive patients

Statins are indisputably the cornerstone of lipid-lowering therapy for prevention of cardiovascular disease. However, it is recognised that certain subgroups of patients may be unable to tolerate a statin, or will be unable to achieve LDL-C goal despite statin therapy. Although ezetimibe is a second…

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).

TAUSSIG – Evolocumab in PCSK9 gain of function mutations

EAS Madrid also offered interesting preliminary findings from the ongoing open-label Phase II TAUSSIG study presented at a latebreaking session.1 Data from five patients recruited in Japan were reported.  In these patients, four had both a PCSK9 gain of function mutation and a LDL-R mutation,…

“Lower is better” for LDL – a new meta-analysis

“Lower is better” for LDL – a new meta-analysis “How low should we go” has long been a key question in dyslipidaemia management. Will achieving levels of LDL-cholesterol well below 100 mg/dL (2.5 mmol/L) provide clinically significant clinical benefits? Will it be safe? A group…

ACC 2014 ODYSSEY MONO: First Phase III data for alirocumab suggests potential as an alternative to statins in hypercholesterolaemia

In this first report of Phase III data, the PCSK9 monoclonal antibody, alirocumab, demonstrated superior LDL-C lowering compared with ezetimibe over 24 weeks, suggesting potential as a treatment alternative to statin therapy in patients with hypercholesterolaemia. ODYSSEY MONO was a randomised, double-blind, double-dummy study in…

ESC Congress 2014: PCSK9 inhibition: continues to show promise for unmet clinical needs

Debate has raged following the launch of guidelines in the US and UK (NICE) which have done away with targets and instead focused on cardiovascular (CV) risk. Yet it should be emphasised that there are also consistencies across the European and US/UK guidelines.1-3  All recognise…

Commentary: Is it clinically relevant to measure circulating PCSK9 levels?

It is well established that PCSK9 acts primarily as a secreted inhibitor of the LDL receptor. The enzymatic activity of PCSK9 allows auto-processing of the PCSK9 precursor within cells [1]. After this initial maturation step, PCSK9 is routed towards the secretory pathway.  Following secretion, PCSK9…

ACC 2014 DESCARTES: Durable LDL-C lowering with evolocumab

DESCARTES (Durable Effect of PCSK9 Antibody Compared with Placebo Study) showed substantial and sustained LDL-C lowering in patients with varying levels of cardiovascular risk. DESCARTES  was a randomized, double-blind, placebo-controlled, phase 3 trial which compared evolocumab with placebo in patients with hyperlipidemia enrolled by 88…

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.

Is the ABCC6 gene important for cholesterol metabolism?

EAS Madrid: What made the clinical news about PCSK9?

TESLA: PCSK9 inhibition effective in homozygous FH Phase III TESLA study shows that treatment with the PCSK9 monoclonal antibody inhibitor evolocumab significantly lowered LDL-C by 31% at week 12 in patients with homozygous FH (HoFH) receiving intensive statin treatment and other lipid-modifying therapy. For the…

RUTHERFORD-2 slide deck now available

New slide set: PCSK9 for LDL cholesterol reduction: what have we learned?

Dr Evan Stein, University of Cincinnati, Cincinnati, Ohio overviews what we have learned so far from trials with the PCSK9 monoclonal antibody therapies. Rationale for PCSK9 inhibition First in man studies Phase II studies

LAPLACE-2 published in JAMA

The LAPLACE-2 (LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy – 2) previously reported at ACC 2014, is now published in JAMA. Robinson JG, Nedergaard BS, Rogers WJ et al; LAPLACE-2 Investigators. Effect of evolocumab or ezetimibe added to moderate or high-intensity…

PROFICIO: Evolocumab reduces Lp(a) in statin-treated patients

In a pooled analysis of 4 phase 2 trials including more than 1300 patients, treatment with the PCSK9 monoclonal antibody evolocumab led to dose-related reductions in Lp(a) which were sustained during longer-term therapy. The pooled population (n=1,359) had a mean age of 56.4 (11.7) years,…

Update on the status of PCSK9 monoclonal antibody therapies

The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) in cholesterol metabolism and the subsequent development of monoclonal antibody therapies is a key example of translational medicine. At least 5 companies now have an agent in clinical trials, with 3 in Phase II development. The…