Eligibility for PCSK9 treatment in 734 Hypercholesterolemic patients referred to a regional cholesterol treatment center with LDL cholesterol ≥70 mg/dl despite maximal tolerated cholesterol lowering therapy

Abstract

BackgroundLDL cholesterol (LDLC) lowering has been revolutionized by PCSK9 inhibitors, Alirocumab (Praluent) and Evolocumab (Repatha), approved as adjuncts to maximally tolerated cholesterol lowering therapy in heterozygous (HeFH) or homozygous (HoFH) familial hypercholesterolemia, and/or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient.MethodsWe applied FDA and insurance eligibility criteria for PCSK9 inhibitor use in 734 hypercholesterolemic patients serially referred over 3 years who then received ≥ 2 months maximally tolerated LDLC lowering therapy with follow up LDLC ≥ 70 mg/dl, and in 50 patients approved by insurance for PCSK9 inhibitors. We documented the percentage of patients with HeFH and/or CVD who met FDA and insurance criteria for PCSK9 inhibitor therapy using LDLC goal-based guidelines.ResultsOf 734 patients with LDLC ≥ 70 mg/dl after ≥ 2 months maximally tolerated LDLC lowering therapy, 220 (30 %) had HeFH and/or CVD with LDLC > 100 mg/dl, meeting FDA-insurance criteria for PCSK9 inhibitor therapy. Another 66 (9 %) patients were statin intolerant, without HeFH or CVD. Of the 50 patients whose PCSK9 inhibitor therapy was approved for insurance coverage, 45 (90 %) had LDLC > 100 mg/dl after ≥ 2 months on maximally tolerated LDLC lowering therapy. Seventeen of these 50 patients (34 %) had HeFH without CVD (LDLC on treatment 180 ± 50 mg/dl), 15 (30 %) had CVD without HeFH (LDLC on treatment 124 ± 26 mg/dl), 14 (28 %) had both HeFH and CVD (LDLC on treatment 190 ± 53 mg/dl), and 4 (8 %) had neither HeFH nor CVD (LCLC 142 ± 11 mg/dl).ConclusionOf 734 patients referred for LDLC reduction, with LDLC ≥ 70 mg/dl after ≥ 2 months on maximally tolerated therapy, 220 (30 %) had HeFH and/or CVD with LDLC > 100 mg/dl, meeting FDA-insurance criteria for PCSK9 inhibitor therapy as an adjunct to diet-maximally tolerated cholesterol lowering therapy in HeFH or CVD. If 30 % of patients with high LDLC and HeFH-CVD are eligible for PCSK9 inhibitors, then specialty pharmaceutical pricing models (~$14,300/year) will collide with tens of millions of HeFH-CVD patients. We speculate that if there was a 50 % reduction in CVD, then there would be savings of $245 billion, in the middle of the range of estimated PCSK9 inhibitor costs of $185-342 billion. Whether the health care savings arising from the anticipated reduction of CVD events by PCSK9 inhibitors justify their extraordinary costs in broad population use remains to be determined.

Efficacy, safety, Low density lipoprotein cholesterol lowering, and calculated 10-year cardiovascular risk reduction of alirocumab and evolocumab in addition to maximal tolerated cholesterol lowering therapy: a post-commercialization study

“…After taking into account the rising CVD costs in the United States, projected by the AHA to be approximately $1 trillion by 2030, we have postulated that the cost to society with an estimated 50% CVD risk reduction with PCSK9 inhibitor therapy [6, 10, 11] would be in the middle of the range of societal costs for CVD [6]. Subsequently, in 103 hypercholesterolemic patients [7] (61 with previous CVD events, first CVD event at median age 55, median LDLC 139 mg/dL despite maximal tolerated cholesterol-lowering therapy), we estimated direct and indirect costs of CVD, cost of estimated next 10-year CVD events, and PCSK9 inhibitor costs to assess whether PCSK9 inhibitors would provide an incremental cost-effectiveness ratio [21] within a society willingness to pay threshold [22].…”

“…Previously, we have projected that an estimated 24 million Americans could be eligible for PCSK9 inhibitor therapy [6, 7]. Prior to commercialization, efficacy and safety of ALI and EVO in patients has been evaluated through randomized controlled clinical trials [8–12], which have stringent inclusion and exclusion criteria, creating a highly selective cohorts of study patients.…”

“…PCSK9 inhibitor therapy could substantially benefit these patients [6]. In the GAUSS-3 study of patients with previous statin intolerance, 43% of patients on atorvastatin had muscular symptoms.…”

Development of proprotein convertase subtilisin/kexin type 9 inhibitors and the clinical potential of monoclonal antibodies in the management of lipid disorders

“…In a recent study on eligibility for PCSK9 treatment in 734 hypercholesterolemic patients referred to a regional cholesterol center with LDLc ≥70 mg/dL despite maximally tolerated statin therapy, and based upon the FDA-and insurance-approved eligibility criteria, Glueck et al51 reported 50 patients approved by an insurance company for PCSK therapy. It is believed that insurance companies may be signing some agreement with pharmaceutical companies for value-based or performance-based sharing risks.…”

PCSK9 Inhibitors Show Value for Patients and the US Health Care System

“…A recent study suggested that even if the drug price of PCSK9 inhibitors could be covered by an annual $245 billion savings in prevented CVD events, the high price of PCSK9 inhibitors still poses a substantial economic burden to the U.S. healthcare system if only accounting for direct medical costs from avoided CVD. (24) Another study suggested these agents may not be cost-effective in patients with FH or ASCVD at current U.S. prices.…”