Hot off the presses, just published today in NEJM. The new drug class PCSK9 inhibitors reduce heart attacks by 15%. Should we all rush out and start on one? Not so fast.
Initial studies demonstrated that Repatha (a PCSK9 inhibitor) dramatically reduced LDL cholesterol levels, but now we have evidence that they reduce the risk of heart attacks. Get ready for the barrage of commercials and ads for Repatha, and get ready for the experts to start proclaiming the benefits of this drug.
But as always, the truth may not live up to the hype.
For starters, the FOURIER trial focused on high risk patients who have already had heart attacks or strokes, and who were already on statins. This is called a secondary prevention trial. It is crucial to point out that it was not a primary prevention trial. The results do not apply to the millions of people with cardiovascular risk factors who have never had a heart attack or stroke (or peripheral vascular disease).
Second, the study did not show any difference in cardiovascular deaths. This is another important point as people frequently equate heart attacks with death. That is not the case. There was absolutely no difference in the risk of dying between the Repatha group and the placebo group.
Third, the reduction in heart attacks, although statistically significant, was small. Over 2.2 years, the risk of heart attacks was reduced by 1.2%. That means we need to treat 66 people for over 2 years to prevent 1 heart attack. Another way to look at it is that 65 people will not get the end benefit, and one will.
Last, the study was only 2.2 years long. The risk of side effects was similar between the two groups, suggesting that PCSK9 inhibitors don’t cause any adverse effects beyond statins. However, this is likely a big question mark regarding these drugs. These drugs drive the LDL lower than any other medication we have ever had. In this study, the average LDL for the Repatha group was 30. Our goal used to be 100, then 70, and now apparently 30. That’s quite a drop.
Is there reason to believe an LDL this low could be dangerous? You bet. LDL, although commonly known is the “bad” cholesterol, is vital for our health. We need it for neurologic and cognitive function. We need it for hormone production. We need it for cell membranes and for absorbing fat soluble vitamins.
Are you satisfied that the drug is harmless after this 2.2-year study? Neither am I. Stay tuned for the discovery of significant adverse effects over the next few years.
So far, I haven't even mentioned cost. If the drug was free, it would still be questionable if it was worth taking. But the drug is most certainly not free. In fact, it costs $14,000 per year.
Since we need to treat 66 people for 2.2 years to prevent one heart attack, that makes it $2.03million per heart attack saved. <Cough> That's a tough pill to swallow.
So why are so many experts going to promote it and extol its benefits? Most physicians believe that medicines are the path to health. The more we can alter our natural environment with drugs the better. Even minimal reductions in our risk are worth the minimal side effects from drugs. That seems to be a common bias in our healthcare system.
My bias is the exact opposite. We can achieve incredible benefits from purposeful lifestyle changes, and all without adverse effects! Drugs are largely unnecessary beyond that. Therefore, in my mind, any drug should have a dramatic benefit and a minimal long-term risk at an acceptable cost. After all, are you interested in lowering your heart attack risk for two-years? Or are you interested in lowering your risk over your lifetime?
Don’t get me wrong. There may still be a very limited role for PCSK9 inhibitors.
For very high-risk patients in whom you have tried everything (especially intensive lifestyle modifications) yet they are still likely to have another heart attack in the near future, then PCSK9 inhibitors could be a good option to reduce their heart attack risk by 0.6% per year, even though it won’t affect their risk of dying.
Beyond that, however, they have no proven benefit and no clear role in medical therapy. They are very expensive, and they are likely going to show significant long-term adverse effects when used for more than 2-years. Tread lightly with PCSK9 inhibitors.
Action item:
When you read the headlines, and hear the news about the incredible benefits of PCSK9 inhibitors, please remember to put it all into context. Use this article as a guide to clarify where the trial has merits and where there are still unanswered questions. As always, if you have any questions, please do not hesitate to contact us at info@DrBretScher.com.
Thanks for reading.
Bret Scher, MD FACC
Cardiologist, author, founder of Boundless Health
www.DrBretScher.com
