$2 Billion Annual Price Tag for FOURIER-Eligible VA Patients on PCSK9 Inhibitor

Approximately 25% of adults with atherosclerotic cardiovascular disease receiving care in the Veterans Affairs (VA) health system would qualify for treatment with evolocumab (Repatha, Amgen), one of the pricey new PCSK9 inhibitors, at a staggering cost of more than $2 billion per year, according to the results of a new analysis.

Alternatively, getting more patients to use high-intensity statin therapy and ezetimibe (Zetia, Merck/Schering-Plough), another lipid-lowering agent soon to be available as a generic, would reduce the number of patients who need the PCSK9 inhibitor as well as substantially reduce costs, say investigators.

“If we were to combine these therapies—that is, put everybody on a high-intensity statin and ezetimibe therapy—LDL cholesterol levels would be reduced below 70 mg/dL in about 60% of patients,” Salim Virani, MD, PhD (Michael DeBakey Veterans Affairs Medical Center, Houston, TX), told TCTMD. “Only about 40% of the initially eligible population would continue to remain eligible for the PCSK9 inhibitor.”

When investigators accounted for costs of titrating individuals to high-intensity statin therapy and the addition of ezetimibe, and then selectively using evolocumab only in patients with LDL cholesterol levels 70 mg/dL or greater, the cost of treatment would be $950 million annually. “Obviously, the question we have, and which we don’t have an answer to, is whether the healthcare system can even absorb this much cost?” said Virani. “It’s an open question. It’s close to $1 billion per year.”

The results of the study were published May 3, 2017, in Circulation.

The FOURIER Trial: Solid Win, Big Costs

In March 2017, the FOURIER investigators presented the highly anticipated results of their large cardiovascular outcomes trial testing evolocumab in patients with stable atherosclerotic cardiovascular disease. After a median of 2.2 years of follow-up, the addition of evolocumab reduced the risk of major cardiovascular events by 15% when compared with placebo.

Even while the results were being celebrated, attention turned to the high costs of the PCSK9 inhibitors, with physicians saying it will be necessary to identify subgroups of patients who might benefit the most from treatment. A yearlong supply of evolocumab and alirocumab (Praluent, Sanofi/Regeneron), the other approved PCSK9 inhibitor, costs approximately $14,000.

In this new analysis, the researchers applied the FOURIER eligibility criteria to a cohort of VA patients. The FOURIER trial included patients with LDL cholesterol 70 mg/dL or higher currently taking lipid-lowering therapy. In the study, a high-intensity statin was preferred, although a moderate-intensity statin equivalent to atorvastatin 20 mg with or without ezetimibe was allowed.

In total, they identified 631,855 veterans aged 40 to 85 years with atherosclerotic cardiovascular disease, of whom 154,823 were eligible for evolocumab using the FOURIER inclusion/exclusion criteria. Of those who qualified, just 49.9% were taking a high-intensity statin and 2.6% were taking a statin/ezetimibe combination.

If the patients were titrated to a high-intensity statin, which is recommended by the American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines, 18.7% of the evolocumab-eligible patients would achieve an LDL cholesterol less than 70 mg/dL, which would make PCSK9 inhibition unnecessary based on the FOURIER inclusion criteria. If ezetimibe were added alone, approximately 50% of evolocumab-eligible patients would lower their LDL cholesterol sufficiently to make the PCSK9 inhibitor unnecessary. Finally, if a high-intensity statin and ezetimibe were both used, 59.8% of patients would no longer be eligible for evolocumab.  

Even assuming a slight VA discount on ($13,462/year), the total cost of treating all FOURIER-eligible patients in the VA system with the new drug would amount to $2.08 billion annually. Conversely, titrating patients to high-intensity statin therapy and adding ezetimibe would reduce the number of evolocumab-eligible patients and result in a cost savings of $1.1 billion, according to the researchers.  

“As healthcare providers, yes, we always look at the effectiveness of therapy and what gives our patients the best benefit, but we have to look at the healthcare system as well and whether we’re going to be able to sustain those costs,” said Virani. “The first and foremost thing we need to do is make sure that patients are on high-intensity statin therapy—if they can tolerate it. If ezetimibe can be added, it’s another tool in the armamentarium and we can use that therapy before we’re actually thinking about PCSK9 inhibitors.”

‘Cost Is a Huge Issue’

Dylan Steen, MD (University of Cincinnati College of Medicine, OH), who was not involved in the study, emphasized the importance of the FOURIER trial, including the reductions in the risk of cardiovascular death, MI, and stroke. He said the study showed that lowering LDL cholesterol to very low levels—down to 30 mg/dL in FOURIER—translates into a significant clinical benefit and was a big win for physicians treating high-risk patients with cardiovascular disease.

Still, the financial impact can’t be overlooked, he said. 

“Cost is a huge issue,” said Steen. “These are expensive drugs. They’re biologic agents. Despite their potency, lowering LDL cholesterol levels 60% and reducing cardiovascular outcomes, we have to figure out who exactly should get these drugs. Clearly they will benefit some people, now that we have the FOURIER results, but to apply [the results] without any consideration of the subject’s risk and LDL levels, among other things, would be inappropriate.”

Steen said the VA analysis is an important contribution in that it “ballparks” the number of PCSK9 inhibitor-eligible patients in a broad cohort of patients, adding that 25% represents a “substantial amount.”

As to why 50% of patients in the VA system were seemingly undertreated with only a moderate-intensity statin, Virani said clinical inertia doesn’t always explain things. Some of these patients are simply unable to tolerate the dose. Virani pointed out that the study also showed adherence to statin therapy was quite poor, with 40.5% of patients not covered by the prescription for 80% of the calendar year.

Similarly, Steen said he and others have looked at practice patterns in the US and UK, with data showing large opportunities for titrating patients to a high-intensity statin or by adding ezetimibe. Getting physicians and patients to make changes to medication regimens, particularly if the patient has been taking a moderate-intensity statin for a while, can be difficult. Tolerability might also be an issue with high-intensity statins, although Steen believes most patients can take the more potent lipid-lowering agent if tried. Ezetimibe, for its part, is essentially a side effect-free drug and can be easily added, he said.

In terms of clinical practice, Steen said that if the goal is to achieve an LDL cholesterol level less than 70 mg/dL, switching to a high-intensity statin and adding ezetimibe is a reasonable approach. Even today, aside from the ACC/AHA guidelines, many groups recommend treating patients to below this threshold.

“Less than 70 mg/dL includes a broad group of people,” said Steen. “That could be an LDL level of 60 [mg/dL] or an LDL of 30 [mg/dL]. What FOURIER and other evidence is teaching us is that an LDL of 60 [mg/dL] is probably not as good as 30 [mg/dL]. So the reality is that if you were to use PCSK9 inhibitors, in many cases, you’d go vastly below 70 [mg/dL] and they’re may be some additional benefit to that. We’re still trying to understand what this relationship is.”