Statins have proved extremely effective for the majority of patients with dyslipidemia and those at high risk of CVD.
However, these drugs are not the complete answer; some patients do not achieve their LDL target even on a high dose, some are statin intolerant, and some have a dyslipidemia for which statin therapy is not the best strategy. New agents have been developed that have the potential to add-in to statins to produce profound LDL lowering and the possibility to raise HDL significantly.
The latter action allows us to address the ‘HDL hypothesis’ that in patients with low HDL, increasing this lipoprotein will generate additional risk reduction.
Dr Barter presented a review of the rationale and testing of CETP (cholesteryl ester transfer protein) inhibitors. Early results have been disappointing – torcetrapib was found to increase CVD risk (possibility as an off-target action) while the outcome trial with dalcetrapib was stopped for futility. Hope remains that the two remaining agents will be successful – results are anticipated for the DEFINE and ACCELERATE trials in 2017.
Novel approaches to the use of omega-3 fatty acids were reviewed by Dr Marchioli. New formulations offer more convenient dosing and a better profile of lipid regulation. A conjugated niacin-EPA compound is an interesting agent for regulation of triglycerides.
Dr Laufs offered insight into PPAR dual agonists and the problems of unwanted side effects and lack of impact on CVD. Ongoing studies focus on the potential benefits of inhibiting lipoprotein-associated-phospholipase A2, and answers to direct effect of these drugs on arterial inflammation will be known in 2014.
Dr Kastelein in assessing new LDL lowering agents picked out Anti-Sense- Oligonucleotides to ApoB and PCSK9 inhibitors as the ones to watch.
These agents are capable of inducing profound LDL reductions but are injectable and their deployment will be a challenge for prescribing physicians used to tablet-based therapy. Achieving ‘neanderthal’ LDL levels is in our grasp if we want it!