Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease

IMPORTANCE Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recently approved for lowering low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia (FH) or atherosclerotic cardiovascular disease (ASCVD) and have potential for broad ASCVD prevention. Their long-term cost-effectiveness and effect on total health care spending are uncertain. OBJECTIVE To estimate the cost-effectiveness of PCSK9 inhibitors and their potential effect on US health care spending. DESIGN, SETTING, AND PARTICIPANTS The Cardiovascular Disease Policy Model, a simulation model of US adults aged 35 to 94 years, was used to evaluate cost-effectiveness of PCSK9 inhibitors or ezetimibe in heterozygous FH or ASCVD. The model incorporated 2015 annual PCSK9 inhibitor costs of $14 350 (based on mean wholesale acquisition costs of evolocumab and alirocumab); adopted a health-system perspective, lifetime horizon; and included probabilistic sensitivity analyses to explore uncertainty. EXPOSURES Statin therapy compared with addition of ezetimibe or PCSK9 inhibitors. MAIN OUTCOMES AND MEASURES Lifetime major adverse cardiovascular events (MACE: cardiovascular death, nonfatalmyocardial infarction, or stroke), incremental cost per quality-adjusted life-year (QALY), and total effect on US health care spending over 5 years. RESULTS Adding PCSK9 inhibitors to statins in heterozygous FH was estimated to prevent 316 300 MACE at a cost of $503 000 per QALY gained compared with adding ezetimibe to statins (80% uncertainty interval [UI], $493 000-$1 737 000). In ASCVD, adding PCSK9 inhibitors to statins was estimated to prevent 4.3 million MACE compared with adding ezetimibe at $414 000 per QALY (80% UI, $277 000-$1 539 000). Reducing annual drug costs to $4536 per patient or less would be needed for PCSK9 inhibitors to be cost-effective at less than $100 000 per QALY. At 2015 prices, PCSK9 inhibitor use in all eligible patients was estimated to reduce cardiovascular care costs by $29 billion over 5 years, but drug costs increased by an estimated $592 billion (a 38% increase over 2015 prescription drug expenditures). In contrast, initiating statins in these high-risk populations in all statin-tolerant individuals who are not currently using statins was estimated to save $12 billion. CONCLUSIONS AND RELEVANCE Assuming 2015 prices, PCSK9 inhibitor use in patients with heterozygous FH or ASCVD did not meet generally acceptable incremental cost-effectiveness thresholds and was estimated to increase US health care costs substantially. Reducing annual drug prices from more than $14 000 to $4536 would be necessary to meet a $100 000 per QALY threshold.