New drugs used alongside statins can lower LDL cholesterol to really low levels, but do the risks outweigh the benefits?
When it comes to “bad” cholesterol, the mantra might be: “How low can you go?”
In a new paper, researchers looked at whether using a drug combo to lower LDL cholesterol to “very-low” or “ultra-low” levels would provide even greater benefits than more modest decreases in LDL.
The manufacturer-funded study, called FOURIER, enrolled more than 27,000 people who were already taking statin drugs to treat their high LDL cholesterol.
Roughly half of these people received injections of evolocumab, a drug made by Amgen and sold under the brand name Repatha. The other half received a placebo, or nonactive, injections.
Evolocumab is a PCSK9 inhibitor, which works by simulating a favorable genetic variation that leads to large reductions of LDL cholesterol.
In an earlier paper for the study, researchers reported that people taking both statins and evolocumab saw their LDL cholesterol level drop dramatically.
At the start of the study, their LDL level was on average 90 mg/dL. This fell to 30 mg/dL after 48 weeks of drug therapy.
Researchers also found that evolocumab reduced the risk of cardiovascular events — such as heart attacks and stroke — by about 15 percent.
So, for about every 67 people treated with the drug, one person avoided one of these events.
But there was no reduction in the risk of death — at least not over the two years that participants in the study were followed.
As the sponsor of the study, Amgen collected and interpreted the study data and helped edit the papers that were published in medical journals.
How low can LDL go?
Research done on cholesterol-lowering statins has shown that the risk of cardiovascular disease decreases at lower levels of LDL cholesterol.
But doctors haven’t known how low cholesterol can go and still reduce risk of heart problems and stroke.
One reason for this is that previous drug studies either didn’t look specifically at outcomes for people whose LDL cholesterol dropped to “very low” or “ultra-low” levels.
Or if they did, there were not enough of those patients to make the statistical analysis useful.
So researchers from the FOURIER study reanalyzed the data with an eye toward these lower cholesterol levels. The results were published Aug. 28 in The Lancet.
The new analysis suggests that the benefits of lowering your LDL cholesterol continue to increase the lower you go, even at ultra-low levels, at least in terms of reducing your risk of developing heart problems or stroke.
There was also no increase in safety concerns for this group, compared with people whose LDL didn’t drop as much.
However, there are some limitations.
Since researchers followed people for only two years, they don’t know if the ultra-low LDL levels translate to a lower risk of dying over the long run.
Some health problems also only show up after taking a drug for years.
And lower LDL cholesterol levels don’t always mean an overall health benefit.
In another unrelated study, the drug torcetrapib reduced LDL cholesterol by 25 percent. But the risk of cardiovascular events and death from any cause increased.
In spite of the dramatic drop in LDL levels, the earlier FOURIER paper and the new analysis leave a big question unanswered: Are the benefits of evolocumab big enough to justify its $14,000 per year price tag?
Health insurers may not be willing to fork out that kind of money — on top of the price of statin therapy — for a treatment that so far hasn’t been found to reduce the risk of death.
Reducing heart disease naturally
One thing that this study does show is that cardiovascular disease is complicated.
The study also brings to light another fact about cholesterol — drugs are not the only way to lower your LDL levels.
Most doctors who prescribe statins for high cholesterol will also recommend that patients exercise more and eat healthier foods.
But more hospitals and doctors’ offices are starting to promote lifestyle changes as a way for patients to reduce their risk of cardiovascular disease — and LDL levels — using diet and exercise alone.
Often this approach involves a whole food or plant-based diet rich in vegetables, fruits, whole grains, beans, legumes like chickpeas and lentils, healthy fats like those in olive oil and avocado, and dairy alternatives.
For many, this diet will be a challenge to switch to. But there is a growing body of research on its benefits.
In one study, people saw their LDL cholesterol level drop by up to 20 mg/dL after one year on a cholesterol-lowering diet.
The catch, though, is that if you go this route, you still have to make smart choices about what to eat.
A study earlier this year in the Journal of the American College of Cardiology found that people who ate a plant-based diet had a lower risk of coronary heart disease.
However, the opposite effect was seen in people who ate a greater amount of less healthy plant foods, such as sugar-sweetened beverages, juices, refined grains, potatoes, and sweets.
So if you’re looking to lower your LDL cholesterol and improve your heart health, talk to your doctor about how diet and exercise can play key roles.