The results are finally in on an eagerly anticipated trial of a new cholesterol-lowering medicine. Many cardiologists are happy with the results, calling the drug a breakthrough. But others are disappointed that the results were not more dramatic.
Lowering Cholesterol with Repatha:
Back in 2015, the FDA approved evolocumab (Repatha) based on the drug’s ability to lower so-called bad LDL cholesterol dramatically. It is intended as a treatment for people with hereditary high cholesterol. One condition of approval was that the manufacturer, Amgen, would conduct a clinical trial to find out whether people would also be less likely to die of heart attacks or strokes.
What the Scientists Did:
The results of that trial, FOURIER, have recently been published in The New England Journal of Medicine (online March 17, 2017). (If you were wondering, FOURIER stands for Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk.)
This randomized trial included 27,564 people at high risk of heart disease. The majority had already suffered at least one heart attack.
Half received high-intensity cholesterol-lowering treatment with a statin and in some cases ezetimibe (Zetia). In addition, they got placebo injections.
The other half received the same aggressive cholesterol-lowering treatment but their injections contained Repatha. After 48 weeks their LDL cholesterol had dropped to unprecedented low levels (the average was 30 but some patients had LDL levels even lower). After two years, heart attacks, strokes and the need for stents were reduced between 21 and 27 percent.
How Cardiologists React to This News:
Some physicians describe these results as spectacular. Others, though, are more cautious. They note that 9.8 percent of the patients getting Repatha and 11.3 percent on placebo experienced heart attacks, strokes, death or hospitalization. That means that roughly 1.5 people out of 100 got benefit.
Relative Risk vs. Absolute Risk:
Many people, including some health professionals, have a hard time reconciling an apparent contradiction. On the one hand, the headlines about Repatha underscored the relative risk reduction of 21 to 27 percent. On the other hand, fewer than 2 percent of the patients actually benefited from taking the drug.
Drug companies like to use relative risk numbers in their marketing efforts. In one striking example, a Lipitor magazine ad proclaimed:
“In patients with multiple risk factors for heart disease, LIPITOR REDUCES RISK OF HEART ATTACK BY 36%*…”
On the surface, this sounds great. Who wouldn’t want to reduce the risk of a heart attack by more than a third? To a lot of people, this sounds like Lipitor would protect 36 patients out of 100 from having a heart attack. That would be terrific, no doubt.
But the asterisk is important. The fine print in the ad went on:
“That means in a large clinical study, 3 percent of patients taking a sugar pill or placebo had a heart attack compared to 2 percent of patients taking Lipitor.”
What this means is that if 100 people took the drug and 100 people took the placebo, there would be 2 heart attacks among Lipitor users and 3 among placebo takers–1 fewer heart attack over the course of the study (which actually had many more than 100 people and ran nearly five years). In other words, 99 people out of 100 who took the drug did not get any obvious heart attack protection. All of a sudden the odds don’t seem as appealing as a 36 percent relative reduction in risk.
This certainly puts the Repatha results in a different light. That is especially true when you consider that in a separate analysis in the FOURIER trial, there was no difference between the two groups with respect to deaths.
Depending upon your perspective, this is either a game changer or a modest benefit for a very pricey medicine. The list price is over $14,000 a year. And patients will need to learn how to self inject the drug either once or twice a month.
Will Your Insurance Cover Repatha?
Insurance companies may not be as enthusiastic about the new cholesterol-lowering drugs as cardiologists. Financial analysts estimate that it could cost as much as $1 million to keep one patient from having a heart attack or stroke. And it might not prevent any deaths. Compared to generic statins, which are inexpensive, this would be a big obstacle to widespread acceptance.
What About Side Effects?
On the other hand, the study did not show any significant increase in adverse effects of Repatha over placebo. The rate of side effects overall was high, however, reaching 77.4 percent in each group. Approximately one-fourth of the subjects suffered a serious reaction, although fewer than 2 percent of them needed to discontinue their injections.
Will Repatha Replace Statins?
Doctors have been eager to find a medicine that could replace statin-type cholesterol-lowering drugs for patients who can’t or won’t take statins. For people who cannot tolerate statins because of muscle pain or weakness, Repatha may indeed offer a way to control cholesterol and reduce the risk of a heart attack or stroke. And for patients who cannot reach their cholesterol-lowering goals with standard medications, the new treatment might offer additional protection. In such instances, insurance companies might get with the program.
The People’s Pharmacy Perspective:
It remains to be seen whether Repatha and similar medications will ever become mainstream treatments for healthy people with high cholesterol.