Results from new studies on cardiovascular prevention are were presented at the 2017 American College of Cardiology Congress in Washington DC – findings from very large studies to test the effects of powerful new drugs to lower cholesterol.
Patients with high blood levels of LDL cholesterol are at higher risk of heart attack, stroke and other serious vascular disorders.
Healthy lifestyle lowers LDL cholesterol. The benefit for cholesterol lowering and the associated reduction in serious cardiovascular diseases is greater the more approaches to a healthy are followed, including Mediterranean-type diet, avoiding tobacco products, regular exercise and moderation in alcohol.
Statins are the most effective current treatment available for patients for lowering LDL cholesterol. However not all patients respond to statins and some patients are unable tolerate statins because of troubling or serious adverse effects.
PCSK9 inhibitors (PSK9i) are a new class of powerful drugs that can cause a major fall in high LDL cholesterol levels: by up to 60% when combined with a statin.
The key questions to be addressed in these studies are whether this “surrogate” end-point of reduced LDL cholesterol translates into clinical benefits for patients – and if so whether the benefits outway risks both to health and in terms of cost-effectiveness, compared to existing treatments.
These biological drugs are given to patients as a treatment by injection because they are designed as monoclonal antibodies (MAbs), proteins which would be inactivated in the gut is swallowed. MAbs use the principle of the body’s own immune recognition proteins, which are able to recognise and limit damage from foreign proteins such as are found in viruses or cancers.
There are usually receptors on liver cells that transport LDL into the liver for it to be broken down, thus keeping the circulating level of LDL cholesterol on check. PCSK9 (proprotein convertase subtilisin kexin 9) is a protein in the liver that inactivates these LDL-scavenging liver cell receptors.
The fewer of these receptors that are present in the liver, the more LDL (“bad”) cholesterol persists in the blood to contribute to the development of disease of the arteries.
Thus PCSK9 inhibitors, by inactivating the PCSK9 protein, allow more receptors to be available to capture LDL for removal from the blood.