"The cholesterol drug that outperforms statins: Patients on the medication are `27% less likely to suffer a heart attack`," the Daily Mail reports.
The drug, evolocumab, makes the liver more effective at removing "bad" cholesterol from the blood.
But the Mail`s headline is somewhat misleading, as evolocumab was given along with statins and not as a replacement for them.
The paper reports on a large trial of more than 27,000 participants at high risk of cardiovascular disease, some of whom had a previous history of events like a heart attack, who were already taking statins to reduce their cholesterol.
Participants across 49 countries were given either injections of evolocumab or an identical dummy injection (placebo) alongside their current statin.
They were followed up for two years. Researchers found evolocumab reduced the risk of cardiovascular death, heart attack or stroke by 20% compared with those taking placebo. There were no serious side effects.
There were signs of a greater benefit over time, so longer follow-up would be useful to provide stronger evidence of an effect, and to also check there are no harms associated with taking the drug over a long period of time.
Overall, however, this research gives hope that this new drug has the potential to reduce cardiovascular events in people who have had an inadequate response to statins.
Current UK guidelines say evolocumab treatment should only be funded by the NHS if a person is at high risk of cardiovascular disease and has persistently high blood cholesterol levels.
Other ways of reducing your cholesterol include eating a healthy, balanced diet low in saturated fats.
Where did the story come from?
The study was carried out by researchers from multiple institutions across the globe, including Harvard Medical School, Brigham and Women`s Hospital, and Amgen in the US, the University of Sydney in Australia, Imperial College London in the UK, and the University of Oslo in Norway.
It was funded by Amgen, a pharmaceutical company, who also had a role in the design of the trial. Many of the study`s authors are working for Amgen or have worked for them in the past.
The media reporting of this story was generally accurate, although the Mail`s comparison of evolocumab with statins is unhelpful.
What kind of research was this?
This randomised controlled trial (RCT) was conducted across 49 countries. Researchers aimed to look at the effectiveness of evolocumab on cardiovascular outcomes compared with placebo in people already taking statins.
Evolocumab is a drug given by injection that lowers low-density lipoprotein (LDL) "bad" cholesterol levels by inhibiting an enzyme called PCSK9.
This enzyme hinders the liver`s ability to remove LDL cholesterol from the body – stopping it working increases the liver`s effectiveness.
The drug has already been found to reduce LDL cholesterol levels by around 60%. It`s currently licensed for use in people with high cholesterol who are either intolerant of statins or haven`t achieved sufficient reduction in LDL cholesterol with statins alone.
As it`s a relatively new drug, its use and potential adverse effects are still being monitored. To date, it`s not yet been established whether the drug prevents cardiovascular outcomes.
An RCT is the best way of testing how effective a drug is, as it reduces the chance of other factors being responsible for any differences seen in the results.
This trial also had the benefit of being double-blinded, meaning that neither patient nor doctor knew whether the person was being given evolocumab or a placebo.
A double-blinded RCT is seen as the gold standard in evaluating a treatment or intervention.
What did the research involve?
The trial included 27,564 participants from 49 countries aged between 40 and 85. Half were randomised to evolocumab, and the other half to placebo.
Evolocumab injections were given either 140mg every two weeks or 420mg every month depending on which the participant preferred. Control participants received matching placebo injections.
All participants had evidence of cardiovascular disease with previous heart attack, a stroke caused by a blood clot, or symptomatic artery disease, along with other risk factors for cardiovascular events.
They were all on some form of lipid-lowering therapy. More than two-thirds were taking a high-dose statin, but those taking a lower dose (for example, at least a daily 20mg dose of atorvastatin) or alternative cholesterol treatment were also included.
Participants all had a fasting LDL cholesterol level of 70mg per decilitre or higher, or otherwise non-high-density lipoprotein (HDL) cholesterol level of 100mg per decilitre or higher, at the start of the study.
The researchers followed participants for an average of 26 months. The main outcome of interest was any major cardiovascular events, which included cardiovascular death, heart attack, stroke, hospitalisation for unstable angina, or coronary revascularisation procedures.
The other outcome of interest was the overall number of cardiovascular deaths, heart attacks or strokes, but not including unstable angina and revascularisation.
What were the basic results?
Evolocumab reduced the risk of the main combined outcomes of cardiovascular death, heart attack, stroke, hospitalisation for unstable angina or coronary revascularisation by 15% (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.79 to 0.92).
To put this in absolute terms, 9.8% of the evolocumab group experienced any of these outcomes compared with 11.3% of the placebo group.
Evolocumab was more effective over time. Compared with placebo, people receiving evolocumab had 16% (95% CI 4 to 26) reduced risk in the first year, increasing to 25% (95% CI 15 to 34) beyond 12 months.
Evolocumab also reduced the risk of the secondary end point (heart attacks) by 20% (HR 0.8, 95% CI 0.73 to 0.88) just looking at cardiovascular death, heart attack or stroke alone.
In actual numbers, 5.9% of the evolocumab group experienced any of these three outcomes, compared with 7.4% of the placebo group.
Similarly, the extent of risk reduction for this outcome increased over time from 12% (95% CI 3 to 20) in the first year to 19% (95%CI 11 to 27) beyond 12 months.
The only adverse events associated with evolocumab were injection site reactions, but these were rare (2.1% of the intervention group versus 1.6% receiving placebo).
How did the researchers interpret the results?
The researchers concluded that, "In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels … and reduced the risk of cardiovascular events.
"These findings show that patients with cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets."
This is a high-quality, well-conducted randomised controlled trial conducted in a very large number of people across multiple countries.
To date, it`s remained uncertain whether evolocumab reduces the risk of cardiovascular events.
This study provides good evidence that the drug reduces the risk of major cardiovascular events in people with high LDL cholesterol levels, and with a high risk of having a cardiovascular event, who are already taking statins.
The follow-up is limited to around two years, during which roughly 1 in 10 people experienced a cardiovascular event.
The reduction in risk was shown to increase over time. Longer follow-up time could allow for further events and so give stronger evidence of whether there`s a clear effect.
Other long-term effects of having evolocumab injections still need to be established – this means ongoing follow-up and monitoring is still needed.
The added burden of having regular injections as well as taking statins is another consideration.
Nevertheless, this study provides hope that evolocumab can further lower cholesterol, and reduce the risk of adverse cardiovascular events, in high-risk patients who have had an inadequate response to statins.
Current UK guidelines published by the National Institute for Health and Care Excellence (NICE) recommend that evolocumab treatment should only be funded by the NHS for people with a high risk of cardiovascular disease who also have persistently high cholesterol levels.