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

Abstract

OBJECTIVES Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the U.S. Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. This study estimates the long-term health and economic value of PCSK9 inhibitors for older Americans (aged 51 and older). METHODS We conducted simulations using the Future Elderly Model (FEM), an established dynamic microsimulation model, to project the lifetime outcomes for the U.S. population aged 51 or older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility; and 2) an extended eligibility scenario which includes patients with no pre-existing cardiovascular disease (CVD) but at high-risk. We assumed the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. RESULTS Utilization of PCSK9 inhibitors by individuals covered by current FDA approval would extend life-expectancy at age 51 by an estimated 1.1 years and would yield a lifetime net value of $5,800 per person. If utilization were extended to those at high-risk for CVD, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. CONCLUSION Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the U.S. healthcare system at the current discounted prices.

The incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: A Systematic Review and Meta-analysis of cost-utility studies

“…Among the twenty studies, twenty-one comparisons were assessed, including sixteen comparisons of PCSK9i versus standard [27][28][29]31,[46][47][48][49][50][51][52][53][54][55][56] ; three comparisons were assessed including PCSK9i versus placebo 17,57,58 and two comparisons were assessed, including PCSK9i versus ezetimibe 30,54 . We considered all studies with PCSK9i versus statin or ezetimibe or placebo for pooling, included the PCSK9i versus no treatment comparator under placebo for pooling 58 .…”

“…All studies were from HICs, except one 52 from a UMIC country. All of the comparisons used model-based economic evaluations, including a Future Elderly Model (FEM) (n=1) 46 , Nor CAD-Norwegian Cardiovascular Disease Model (n=1) 51 , SMART-REACH Model (n=1) and Cardio Vascular Disease Policy Model (CVDPM) (n=4) 30,54,55 .…”

“…All studies used discounting for costs and outcomes, except for one study 48 . Sources of data for model input parameters were based on multiple-study-based estimates for the majority of studies 27,28,30,46,47,[49][50][51]54,[56][57][58][59] expect five studies which used synthesis-based estimates 29,31,48,52,53 and two studies used single-studybased effectiveness 55,60 . All the studies reported the use of country-specific thresholds as the willingness to pay (WTP) except one study that used GDP based WTP 46 .…”

Higher responsiveness to rosuvastatin in polygenic versus monogenic hypercholesterolaemia: a propensity score analysis

“…Undoubtedly, severe hypercholesterolemia must be treated, irrespective of the underlying genetic cause due to the causal role of elevated LDL-C in the development of atherosclerosis. All of the patients with hypercholesterolemia should reach recommended LDL-C treatment targets to improve their clinical outcome [25,35,36]. However, different approaches can be proposed for monogenic and mutation negative FH cases and in consequence for those with polygenic cause of FH due to higher CV risk in HeFH [37].…”

“…In the era of a personalised medicine approach, when genotype helps to tailor patient's treatment, and in healthcare systems with limited financial resources, the results of our study would help to identify those patients who will benefit the most from early, intensive therapy with PCSK-9 inhibitors [35,36,38]. Further prospective studies in a larger number of patients with polygenic hypercholesterolemia and monogenic FH would provide more information and evaluate the LDL-C response to oral lipid-lowering medications and PCSK-9 inhibitors, and to assess their CV risk.…”