A new class of powerful cholesterol-lowering drugs really can do what they ultimately were designed for: Reduce death, heart attacks, strokes and similar bad outcomes in patients who have had a heart attack or stroke, a new study says.
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The research is expected to increase use of the injectable drugs for high-risk patients with hardening of the arteries — or atherosclerosis — who can’t get their bad LDL cholesterol low enough by statin drugs alone.
“This study shows that adding an injectable cholesterol-lowering drug to the standard treatment of statins substantially reduced the risk of a second heart attack or stroke,” says cardiologist Steven Nissen, MD.
Dr. Nissen, Chairman of Cardiovascular Medicine at Cleveland Clinic, has been involved with studies of the drugs, called PCSK9 inhibitors. The study was published late last week in the New England Journal of Medicine.
Approved but not widely adopted
The new study could be a milestone for the PCSK9 inhibitors. Two of these drugs — evolocumab, which is sold under the brand name Repatha®, and alirocumab, which is sold under the brand name Praluent® — received approval from the Food and Drug Administration (FDA) in 2015. The approval was based on their ability to lower LDL cholesterol by as much as 50 percent to 70 percent when used in combination with statins. That’s considerably more cholesterol-lowering punch than had been shown by any drugs before.
A study published last fall found that when evolocumab was added to a statin, it reduced the amount of plaque clogging patients’ arteries — essentially reversing their heart disease. The evolocumab-statin combo also lowered patients’ average LDL cholesterol level to 36.6 mg/dL.
“No one had ever reached levels that low in a clinical trial,” Dr. Nissen says.
Yet physicians and insurance companies have been slow to promote use of the PCSK9 inhibitors, in part because these drugs are expensive. But they also hadn’t achieved the holy grail of cholesterol therapies — evidence in a clinical trial that their cholesterol-lowering effects translate to a reduced risk of cardiac outcomes like death, heart attack and stroke in patients who take the drugs.
“It takes a while to gather this type of evidence,” Dr. Nissen says, “because patients need to be followed for at least a couple of years while taking the drug to see whether these events are happening.”
What the study found
The new study involved more than 27,500 patients who had had a heart attack, stroke or other serious disease of the arteries. All had an LDL cholesterol level of 70 mg/dL or higher. In addition to conventional statin therapy, patients were randomly assigned to receive either evolocumab or a placebo.
After two years of therapy, the patients taking evolocumab were 15 percent less likely than patients taking placebo to experience death, heart attack, stroke, hospitalization for angina or the need for a heart bypass or angioplasty.
Patients who took evolocumab saw their median LDL cholesterol levels drop from 92 mg/dL to 30 mg/dL over the two-year study while levels in the placebo group basically held steady.
The two groups had no notable differences in side effects.
Things to know about the PCSK9 drugs
“Despite the study’s first-time evidence that a PCSK9 drug can be added to a statin to significantly lower patients’ risk following a heart attack or stroke, these new drugs are not for everybody,” Dr. Nissen says. “But for people who are at very high risk, it’s worth having a discussion with your physician about whether or not you might benefit from additional lowering of your LDL cholesterol.”
He adds four more key points about PCSK9 drugs:
- They’re currently approved for use only in combination with statin therapy and diet to lower LDL cholesterol.
- They are well tolerated and show no evidence of producing the muscle side effects reported by some people who take statins.
- They are taken by a simple method of self-injection every two weeks or once a month.
- The drugs’ price tag of about $14,000 a year without rebates or discounts.
“This study now gives us the data we need to better work with insurers to make sure that the patients who need these medications to reduce the risk of a second heart attack or stroke can access them,” Dr. Nissen says.