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, nonfatal myocardial 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.