Sunday, October 17, 2021
HomeCardiologyCholesterol-cutting injections may cut risk of heart attacks

Cholesterol-cutting injections may cut risk of heart attacks

A new, currently-unlicensed drug treatment that works by "silencing" genes can help to halve levels of LDL cholesterol with just two injections per year, according to a study. The findings come from the largest clinical trial to date of the cholesterol-lowering drug inlcisiran, which helps patients to reduce their LDL-cholesterol, or so-called "bad cholesterol".

In a phase III study of more than 1,600 patients with increased risk of cardiovascular disease and taking statins, researchers found that giving regular but infrequent doses of the drug helped to reduce LDL-cholesterol by half on average. Researchers believe the drug could help more patients who are unable to take statins or who fail to take their current cholesterol-lowering medication properly.

Professor Kausik Ray, from Imperial College London School of Public Health and principle investigator of the Orion-11 trial, presented the findings this week at the during a late-breaking session at the European Society of Cardiology Congress 2019 in Paris.
“The cumulative effects of long-term uncontrolled LDL cholesterol continue to place millions of people at increased cardiovascular risk,” explained Ray. He added that the treatment provided assurance that cholesterol can be lowered “in a sustained fashion over the long-term with an infrequent dosing regimen”.

In the trial, 1,617 patients received infrequent injections of inclisiran (300 mg) over the course of a year – at the start, then three months later, and then every six months.

The new data show that patients taking the treatment had sustained reductions in their cholesterol levels (by an average of 50 per cent) over the course of 18 months, compared to patients on statins and taking a placebo injection. In addition, the treatment was shown to be safe over the period, with few adverse events. The findings will now be submitted to a peer-reviewed journal, where the full study findings, including limitations, will be published.

Currently, millions of patients in the UK are eligible to take cholesterol-lowering medications, such as statins, every day to reduce their LDL-cholesterol, and reduce their long-term risk of cardiovascular disease. But many patients may not take their medication as advised – taking it infrequently or failing to take it at all – meaning the treatment is not as effective due to poor adherence.

To tackle the problem of poor patient adherence, scientists are exploring new classes of longer-lasting treatments which could be delivered less-frequently, but maintain the therapeutic effect of daily medication.

One of these drugs is the PCSK9-inhibitors, part of a class of drugs called RNA interference therapies (siRNA). These treatments target key proteins, effectively silencing the genes which produce it.

The PCSK9 protein breaks down receptors on the surface of liver cells which help to remove LDL cholesterol from the blood. But short fragments of RNA – the molecule which carries information from the genes to the cell’s protein-making machinery – can be used to target and ‘silence’ the gene which encodes the protein, stopping PCSK9 from being made and so stopping the receptors on the cells from being broken down. The result is a sustained reduction in cholesterol levels.

Inclisiran is not currently available in the UK and needs to be approved by the UK regulator before it could be made available on the NHS. However, the latest findings add to growing evidence which show that the treatment is safe and effective in patients and move it further along the process.

Ray added: “This is a ground-breaking new approach for preventing atherosclerotic cardiovascular disease with exciting implications at a population health level.”

The study was sponsored by the drug-maker, The Medicines Company.

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[link url=""]Imperial College London material[/link]
[link url=""]ESC Congress 2019 abstract[/link]

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