How Many Americans with High Cholesterol Could be Eligible for PCSK9 Inhibitors?

Two new PCSK9 inhibitors, Praluent (alirocumab) and Repatha (evolocumab), were recently launched for patients at high risk of atherosclerotic cardiovascular disease (CVD) not adequately controlled with diet and maximally tolerated lipid lowering therapy.

Research published in Lipids in Health and Disease explained that PCSK9 inhibitors are approved for patients with heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH), and for patients unable to achieve LDL cholesterol (LDLC) goals with maximal tolerated diet-drug cholesterol-lowering therapy, including patients who are statin intolerant.

More conclusive studies are needed to focus on CVD events, but preliminary controlled clinical trials for safety and efficacy have shown PCSK9 inhibitors reduce the risk of CVD by about 50%.

PCSK9 inhibitors also carry an annual cost of $14,000 to $14,600 per patient, causing investigators to wonder how many hypercholesterolic patients potentially could be prescribed these expensive specialty drugs.

To answer this question, researchers conducted a study of 734 patients referred to a cholesterol diagnosis and treatment center in Cincinnati from May 2012 to September 2015.

Patients eligible for the study received ≥ 2 months of maximally tolerated diet-drug LDLC lowering therapy, with last follow up LDLC ≥ 70 mg/dl. All patients had received diet instructions from a registered dietician and most were statin users. Of these patients, 179 (24%) were statin intolerant, defined as a demonstrated intolerance to ≥ 3 statin medications.

Findings on Patients Not Reaching LDLC Goals

Of the 734 hypercholesterolic patients not well managed with traditional therapies, 210 (29%) had HeFH.

Meanwhile, 180 (25%) had CVD events in their medical records, including coronary artery, carotid, aortic, or peripheral vascular artherosclerosis, transient ischemic attack, or ischemic stroke. Median age at the first CVD event was 55 years.

Sixty-six of 734 (9%) patients were statin intolerant without HeFH or CVD.

After ≥ 2 months of diet-drug lipid lowering therapy, median LDLC in patients with HeFH was 127 mg/dl; 101 mg/dl for patients with CVD; and 123 mg/dl for patients who were statin intolerant.

Applying FDA and insurance criteria, this study identified 220 patients (30%) who would be eligible for PCSK9 inhibitor therapy. Eligibility was defined as HeFH and/or CVD with LDLC > 100 mg/dl, despite maximally tolerated diet-drug therapy.

Fifty patients participating in this study actually were approved by their insurance carriers for PCSK9 inhibitor therapy. Of these, 45 (90%) had LDLC > 100mg/dl after ≥ 2 months of lipid lowering therapy, and 5 had LDLC 80-100 mg/dl. 17 (34%) had HeFH with no CVD; 15 (30%) had only CVD; 14 (28%) had HeFH and CVD; and 4 (8%) had neither.

PCSK9 Inhibitor Discussion

This study, focused on high-risk patients for whom PCSK9 inhibitors are indicated, found that 30% of hypercholesterolic patients not well managed by traditional therapies were eligible for new specialty drugs Praluent or Repatha under current FDA and insurance guidelines.

Extrapolating this 30% prevalence to the US population (78 million hypercholesterolic adults), authors estimated that 11% of the entire US population, or 23.4 million adults, could be eligible to use PCSK9 inhibitors as an adjunct therapy.

Authors noted that the population cost of these new specialty drugs will depend on how CVD risk and LDLC thresholds are defined, going forward. Considering all the different approaches found in existing literature, they concluded that anywhere from 13 to 23 million Americans might be candidates for PCSK9 inhibitor adjunct therapy.

In their cost-benefit analysis, authors concluded that the extraordinary cost of $185 to $342 billion spent on PCSK9 inhibitors could be offset partially by a societal cost savings (direct and indirect) of $245 billion, derived from an estimated 50% reduction in adverse CVD events. Whether or not this justifies broad use of expensive specialty drugs remains to be seen, the report noted.