Currently, statin therapy is the standard treatment for many patients with high cholesterol. But a new study led by Dr Marc Sabatine, a senior physician at Brigham and Women's Hospital in Boston, and colleagues, claims a drug called evolocumab could be much more effective; it reduced cholesterol levels so dramatically that patients' risk of cardiovascular events – such as heart attack and stroke – fell by more than half, compared with those receiving standard therapy alone.
The study was a 1-year extension of 12 phase 2 and 3 clinical trials that had assessed evolocumab's ability to reduce levels of low-density lipoprotein (LDL) cholesterol – commonly referred to as "bad" cholesterol because of the role it plays in blocking the arteries. The 4,465 patients involved in the study had been a part of at least one of the previous trials investigating evolocumab, which works by blocking a protein that stops the liver from removing LDL cholesterol from the blood – called proprotein convertase subtilisin-kexin 9 (PCSK9).
Of the participants, 2,976 were randomised to receive an injection of evolocumab under the skin every 2 or 4 weeks plus standard therapy, while 1,489 patients received standard therapy alone, which mostly involved moderate- or high-intensity statin therapy. The average follow-up duration was 11.1 months.
The study was open-label, meaning the participants were fully aware of the treatment they were receiving, as were the researchers. However, a central committee that reviewed the data – assessing the effects of evolocumab on LDL cholesterol levels and reporting any cardiovascular events during follow-up – was blinded to the treatment groups.
At study baseline, the average LDL cholesterol level among participants was 120 mg/dL, which the researchers say is similar to the average level found among the general population.
However, the team found that patients treated with evolocumab experienced an average 61% reduction in LDL cholesterol levels. Within 12 weeks, LDL cholesterol levels reduced to less than 100 mg/dL – defined as the optimal range – in 90.2% of evolocumab-treated patients, while levels reached 70 mg/dL or less for 73.6% of patients who received the drug. These reductions were sustained throughout the entire follow-up period, the researchers report.
In comparison, only 26% of patients who received standard therapy alone saw their LDL cholesterol levels fall below 100 mg/dL, while only 3.8% had such levels fall below 70 mg/dL.
What is more, compared with patients who received standard therapy alone, those treated with evolocumab experienced a 53% reduction in cardiovascular events, including heart attack, stroke, hospitalisation, angioplasty and death; evolocumab-treated patients had a 0.95% risk of a cardiovascular event during follow-up, while standard-therapy patients had a 2.18% risk.
The team says these results remained even after accounting for patients' age, baseline LDL levels, statin use, primary or secondary prevention and incidence of valve disease. Evolocumab was also found to be well tolerated by patients.
However, the researchers admit their study is subject to some limitations. They note, for example, that the number of cardiovascular events in the study was relatively small, with only 60 identified.
Still, the team believes the findings show that not only is evolocumab effective for dramatically reducing cholesterol levels, but it may be effective for rapid risk reduction of cardiovascular events.
The researchers note that because evolocumab works differently to statins – which block an enzyme in the liver that is responsible for making cholesterol – the drug also holds hope for patients who do not respond to statins or who are unable to tolerate them.
Evolocumab is currently undergoing further testing in a clinical trial involving more than 27,500 patients, the results of which are expected in 2017. Though Sabatine notes that no definitive conclusions about evolocumab's effectiveness can be made until then, this current study shows promise.
[link url="http://www.medicalnewstoday.com/articles/290936.php"]Full Medical News Today report[/link]
[link url="http://www.nejm.org/doi/full/10.1056/NEJMoa1500858#t=articleTop"]New England Journal of Medicine article[/link]