Lipid research
Those of us who have been treating patients with high cholesterol levels, in some of whom this was genetic (Familial Hypercholesterolaemia or FH), were frustrated “in the old days” by absence of a powerful cholesterol lowering drug.
When statins became available in the 1990s, and some of us had taken part in the initial evaluation of the early statins, the game changed for the patients and for and their medical carers. Statins were found to reduce cardiovascular events dramatically.
However even large dose statins failed to reduce the LDL cholesterol levels adequately in some patients with very high levels especially in those with FH, and some patients were found to be intolerant to statins.
We were therefore excited and delighted when a new class of drug became available for testing in the last decade. We participated in the evaluation of 3 monoclonal antibodies which targeted a molecule called PCSK9. Whereas statins inhibit the synthesis of cholesterol and hence activate the LDL receptors that remove circulating LDL, the inhibition of PCSK9 preserves the lifetime of LDL receptors. Patients with FH have a deficiency of LDL receptors but the increased recycling of those receptors made possible by inhibiting PCSK9 which normally degrades the receptors, results in LDL cholesterol levels being reduced to very low levels. Two large trials reported within the last 12 months have shown that this can reduce heart attacks and other cardiovascular events significantly.
The drug is expensive and currently available only for those patients with severe FH. We have been able to help about 30 such patients.
In the last decade, Cardiology staff have been involved in a number of other clinical trials, usually as part of an international program of cholesterol or triglyceride lowering drugs. This has included so-called CETP inhibitors that raise HDL as well as lowering LDL, high dose fish oil that reduces triglycerides, both of which may be expected to lead to fewer heart attacks. However the CETP inhibitors although successfully raising HDL substantially have resulted in inconsistent trial outcomes and my not be marketed. We are currently about to test a new class of LDL lowering drug.
