Fourier Study Outcomes: Are PCSK9 Inhibitors Worth the Cost?

Since the PCSK9 inhibitors were released last year, health plans have tried every trick in their toolbox to prevent the use, or in their opinion, the overuse, of these remarkable drugs. At the time of approval by the FDA, the data demonstrated dramatic reductions in low-density lipoprotein cholesterol (LDLC) but no long-term benefit in terms of reduction in cardiovascular events. Since the LDL reduction was an interim measure, many plans were waiting for longer term, outcome-based proof. Well, now they have it in the form of the FOURIER study, which was published recently in New England Journal of Medicine and also released at the American College of Cardiology. 

This study enrolled over 27,000 patients (median age 62) with known cardiovascular disease who were also on a moderate-to high-intensity statin regimen at over 1200 sites in 49 countries. More than four-fifths of the patients had a history of a heart attack , one in five had suffered an ischemic stroke, and 13% had symptomatic peripheral artery disease. The median LDLC was 92 mg/dL. The patients were randomized in a one to one manner to receive either evolocumab or matching placebo… basically about 13,780 in each group. 

The results on the LDLC were remarkable—a median of 30 mg/dL was achieved and remained steady for the entire trial. The primary endpoint was a composite score that included: heart attack, stroke, and hospitalization for angina, revascularization or cardiovascular death (Table). Of the patients, 11.3% of the placebo group and 9.8% of the active arms had one of these endpoints; a reduction of 15% overall. There was also a 25% reduction in cardiovascular death, heart attack, or stroke (the secondary endpoint) after the first year. Further analysis demonstrated no effect on cardiovascular death by itself, but the reduction in the other two components of the composite endpoint was 27% reduction in AMI and 21% reduction in stroke.  

Sample of Actual Data

The placebo and active arm had similar adverse event data. The list price of evolocumab is roughly $15,000 per year.  Obviously the actual cost will be less due to special deals, negotiated rebates, etc.

If you look at the composite score, for every 1000 patients treated, a total of 15 will avoid a heart attack, stroke, or hospitalization for angina or revascularization—with mortality rates that are basically identical.  

But, the yearly cost is approximately $15,000 times 1000 patients, at a cost of $15 million—all to save 15 events.

So the cost for each event avoided was $1 million and these were not deaths, but events. If you read the fine print, only about 70% of the patients were on an intense lipid regimen. Additionally, 80% had hypertension and 37% had diabetes. 

Now we know that at least in those with prior cardiovascular disease, for $1 million you can prevent a heart attack, stroke, admission, or revascularization.

Not much of a bargain considering our country is already $19 trillion in debt. The patients were a pretty sick group who were also not achieving their LDLC goal. Did anyone ever rate their adherence to the meds and other treatment they were receiving for their LDL and their diabetes? And why should anyone enroll a smoker?  I know I am showing my bias but, lets get real here, are there lifestyle changes that could be made to prevent even a few of the events?  

My Take on The FOURIER STudy

I’m a grandparent of 12 children and if I was given $1 million to prevent a heart attack, I would put it into my grandkid’s college fund, not into a drug that may or may not allow me to live 1 more day. I personally feel we cannot afford this class of drugs given their rather mediocre response at this rather exorbitant cost. I would rather invest in the future, not the past.  

When will America start to treat medical endpoints in a logical, economic manner?  And when will we wake up and realize that we have a finite amount of  resources and an infinite amount of medical desires.