The PCSK9 LDL drugs do not cut heart risk in half
March 18, 2015- Op-Ed by Steven E. Greer, MD
The American College of Cardiology (ACC) meeting is underway, and the main Late Breaking data making the national news came from the PCSK9-antibody drugs (evolocumab and alirocumab) that dramatically lower LDL cholesterol. Presumably, LDL is a reliable surrogate marker for heart disease, according to the studies author. Therefore, this dramatic lowering in LDL means that the new class of drugs will be game changers, according to them.
The mainstream news ran with the weekend press releases from the ACC and regurgitated them without any critical analysis, as usual. CBS’ Dr. John Lapook, like many others, stated that the studies showed the drugs “cut the risk of heart attack and stroke in half”. Despite no drug in cardiology ever showing more than a few percentage points in risk reduction in high-risk patients, the mainstream news TV doctors did not question this outlandish claim of a 50% reduction in risk.
The studies presented at the ACC were not designed to show overall survival benefits or risk reductions. So, where is this “cut the risks in half” claim coming from?
We were scheduled to interview Dr. Evan Stein, the Principal Investigator for the Amgen drug trial in evolocumab, but he backed out at the last minute. Instead, we began an email debate. We asked him to explain the claims in the press about the large risk reductions.
Dr. Stein replied, “…why the early data from PCSK9 inhibition looks promising for reducing CVD events - although as we point out in our article the numbers of events are small but at least moving in the right direction. The percentage reduction of events is purely a mathematical relationship to mg/dL (not %) decrease in LDL cholesterol, time, and global risk for CVD, which is not rocket science but is outlined in the attached article I wrote with a colleague from my original lipid clinic I started in 1972 in Johannesburg.”.
So, the wild claim that PCSK9 drugs seemingly cure the world of heart disease is based on one black box unproven theoretical formula. This is classic “junk in, junk out” math. The authors were also using the old statistical ploy of relative risk. The “small number of events” could have been cut from two heart attacks to one, showing a “50% reduction” (we do not have the actual data from the ACC. This is just an example).
When we asked Dr. Stein to step back and explain why LDL is even a valid surrogate marker for heart risk, despite leading authorities, such as Harlan Krumholz from Yale, calling for the end to LDL markers, Dr. Stein replied, “If you promise to behave rationally and are prepared to listen to and read the science, I would be happy to spend as long as it takes to try to help you understand why LDL cholesterol has been repeatedly proven to be one of, if not the, most reliable (and modifiable) surrogates for CVD over the last 30 years (even prior to statins).” So, in other words, he dodged the question.
For decades, the hundreds of billions of dollars generated by Lipitor and other statin drugs thoroughly corrupted the field of cardiology. Millions of people have been placed on statins for primary prevention despite no studies showing any befit. Once Lipitor came to an end with patent expiration, cardiologists began to speak out against the futility of chasing high cholesterol numbers. In fact, both the AHA and ACC radically altered their guidelines on how to treat cholesterol, diminishing the role of LDL surrogate markers.
However, that brief renaissance of ethical scientific thought lasted just one year because the PCSK9 drugs began to develop in the clinics. Their trials were based solely on LDL surrogate markers and not actual heart even outcomes as the primary endpoint. Likely to be priced at $10,000 a year as large molecule injectable drugs, the lobbyists from Amgen, Regeneron, Sanofi, and others took control over the cardiology societies once again. The annual meetings, such as the ACC, are funded by the drug industry, and they ceased being “academic meetings” long ago, and are not just industry trade shows.
The FDA has the ability to shut down what threatens to be a new era of unnecessary cholesterol treatment that will cost hundreds of billions to the taxpayer. The agency should demand that the clinical trial used for approval show actual reductions in heart attack, or increased survival, and not allow surrogate LDL markers to be used instead.
Cardiology, Cardiology/interventional, FDA, Internal medicine, NEJM, Op-Ed, Policy | apples49 | 
April 14, 2015 7:58 pm
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