Long-awaited clinical trial results have shown that a new cholesterol lowering drug could further reduce the risk of a heart attack or stroke for those already taking statins.
The result of the FOURIER study of evolocumab means the use of this type of drug (human monoclonal antibody) have taken a step closer to being used in routine treatment to treat heart disease.
The study of 27,564 patients living with heart disease and taking statins found the drug lowered cholesterol by an average of 59% and reduced the risk of a heart attack or stroke in two years of follow-up.
A second study, the EBBINGHAUS cognitive function trial, which was simultaneously conducted in FOURIER patients, also achieved its primary endpoint, demonstrating that evolocumab was non-inferior to placebo for the effect on cognitive function.
Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.
Evolocumab is approved in more than 40 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union. Applications in other countries are pending.
Speaking on the results Professor John JP Kastelein said: "Because LDL-c levels were very low in the FOURIER trial, this shows how safe that is. The observation that both primary and secondary endpoints showed positive results, means that CV mortality and stroke were also positive. That implies that lowering LDL-c levels also lowers the risk of stroke and mortality."
The British Heart Foundation’s Medical Director, Professor Sir Nilesh Samani, said: “This trial is a significant advance as it found that giving patients evolocumab, a PCSK9 inhibitor, on top of statins not only helped to further reduce LDL-cholesterol but also reduced the risk of cardiovascular events in people already affected by heart disease, without causing major side effects.
“However, the trial was stopped early, after only 2.2 years of average follow-up, and therefore it is difficult to be certain about the extent of the longer term benefit, including the impact on dying from heart disease, as well as longer term safety. These are important considerations when these drugs are approved for clinical use.”
The results of the FOURIER study of evolocumab were published in the New England Journal of Medicine.