It may seem obvious that lowering LDL cholesterol would inevitably reduce the risk of heart disease. But drugs can be unpredictable. They tend to have many effects. A drug that ameliorates one risk factor might have other effects that offset the benefit.
On Friday, investigators reported the results of a highly anticipated trial of a PCSK9 inhibitor called evolocumab (brand name Repatha). This medication reduced LDL levels to an almost unfathomable 30 mg/dl from about 90 mg/dl on average, which is typically considered low.
Over about two years of study, the researchers found that the new drug, when added to statin therapy, further reduced the risk of heart attack or stroke by about 15 percent. For about every 70 people treated with the drug, one person benefited in this way. This is not far off the size of the benefit that statins provide.
So the drug works, which is good news for patients. And no safety concerns emerged. But the applause from heart experts has been muted, because expectations were so much higher. Their hope had been that drastically low LDL cholesterol levels would make it difficult — or even impossible — to have a heart attack.
Where does that leave someone contemplating whether they should add this drug to an existing regimen?
For people with a high risk of heart attack or stroke, there is now evidence that evolocumab may help you dodge the bullet. It is not a panacea, and you need to decide whether the odds sound good: You may be the lucky one among about 70 people who take the drug. The benefit is likely to be greatest among those with the most risk, including people with very high LDL levels despite treatment.
Still, the cost is sky-high. Not all insurance companies will consider this drug a reasonable value, and some experts already think that the price should come down, given the size of the benefit. On the positive side, there was some indication that the benefit was increasing over time, but that is highly speculative at this point.
Another reason to hesitate: The study’s short time frame means that there wasn’t much time in which to detect safety problems. If you are cautious about the safety of medications, you may want to wait and see what happens as more people start using it.
Besides, there is a much less expensive alternative to evolocumab. Ezetimibe (Zetia) is another medication that can be added to statins to further reduce cholesterol. One study has indicated that it can reduce risk when added to statin therapy, though not quite as much as evolocumab did.
For people with a low risk of heart disease, there is probably little to gain from taking a PCSK9 inhibitor. Many, many of these kinds of patients would have to be treated for someone to benefit. And there are no trials yet in this population.
What about people who have trouble with statins? First, it turns out that some of the perceived problems with statins are not related to statins at all; you may need help from your doctor to determine what’s really causing your symptoms. And some people tolerate one statin better than another.
If statins are really not for you, ezetimibe is an option. If you still want to further lower risk, then you might add evolocumab, despite its expense, to ezetimibe. This can be a particularly important option for people at high risk because of very high LDL levels.
There are not yet studies of outcomes in patients who use these medications because they cannot take statins. But it is a reasonable guess that the benefit will be similar to that reported in the newly released study — about a 15 percent reduction in heart attacks or strokes.
If there is a silver lining, it’s that the tried-and-true remedies are highly effective at reducing the threat for those at great risk of heart attack and stroke. Despite the newest drugs, a combination of heart-healthy behavior, blood pressure control and statin therapy remains the gold standard.
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