Contemporary National Patterns of Eligibility and Use of Novel Lipid‐Lowering Therapies in the United States

Abstract

Background The emergence of PCSK9i (proprotein convertase subtilisin kexin type 9 inhibitor) and icosapent ethyl (IPE) has expanded the role of lipid‐lowering therapies beyond statins. Despite recommendations by clinical practice guidelines, their national eligibility and use rates remain unclear. Methods and Results In the National Health and Nutrition Examination Survey data from 2017 to 2020, we assessed eligibility and the use of statins, PCSK9i, and IPE among US adults according to American College of Cardiology/American Heart Association guideline recommendations. Eligibility for PCSK9i and IPE were determined in the following 2 scenarios: (1) assuming existing lipid‐lowering therapy as the maximum tolerated before assessing eligibility for novel therapies and (2) assessing eligibility after assuming initiation and maximal escalation of preexisting lipid‐lowering therapies and accounting for expected lipid improvements. Of 2729 sampled individuals, representing 149.3 million adults, 1376 had indications for statins, representing 65.8 million or 44.0% (95% CI, 40.9%–47.2%) of adults. Current statin use was 45% of those eligible and was low across demographic groups. A total of 9.7 and 11.6 million adults would benefit from PCSK9i and IPE, respectively, based on lipid profiles and existing therapies. Assuming maximal escalation of statins and addition of ezetimibe, 4.1% (95% CI, 2.8%–5.4%) of adults or 6.1 million would benefit from PCSK9i and 6.8% (95% CI, 5.4%–8.3%) or 10.2 million from IPE. Conclusions Six and 10 million individuals have clinical profiles whereby PCSK9i and IPE, respectively, would be expected to improve cardiovascular outcomes even after maximum escalation of statins and ezetimibe use, but remain undertreated with lipid‐lowering therapies. Optimal use of lipid‐targeted agents that include these novel agents is needed to improve population health outcomes.

Low-Density Lipoprotein Cholesterol Levels in Adults With Coronary Artery Disease in the US, January 2015 to March 2020

“…This is concerning because evidence suggests LDL-C levels are improving in the overall population . Factors contributing to low rates of attaining guideline goals may include inadequate statin treatment intensification, insufficient add-on therapy use (eg, ezetimibe), and low use of novel therapies (monoclonal antibody PCSK-9 inhibitors, inclisiran, and bempedoic acid) . Low rates of statin use and intensification may relate to prescriber or patient hesitation.…”

Global eligibility and cost effectiveness of icosapent ethyl in primary and secondary cardiovascular prevention

“…Variation in IPE eligibility largely depended on whether studies used highly selected patient populations (eg, history of CABG) vs. broader populations (eg, general adult population); which and how many of the REDUCE-IT, regulatory label, or guideline criteria were used; and whether studies assessed IPE eligibility in primary, secondary, or both prevention settings. Importantly, some of the most common reasons for IPE ineligibility were that patients did not meet TG and LDL-C criteria ( 41 , 47 , 48 ), suggesting that existing lipid-lowering therapies such as statins remain underused ( 59 ).…”

“…Using data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020, Shen et al ( 59 ) investigated eligibility and use of lipid-lowering therapies, including statins, IPE, and proprotein convertase subtilisin/kexin type 9 inhibitors, among US adults. Eligibility criteria for IPE were based on the scientific statement from the National Lipid Association ( 33 ), which included patients treated with moderate- to high-intensity statins aged forty-five years or older with clinical ASCVD or aged fifty years or older with diabetes and at least one additional CV risk factor (eg, hypertension, current cigarette smoking, low high-density lipoprotein cholesterol, advanced age, residual TG 135–499 mg/dl even after statin treatment) ( 59 ). Of 2,729 sampled individuals (or 149.3 million US adults), forty-four percent ( n = 1,376) had had an indication for statins (or 65.8 million US adults), but only forty-five percent of these had taken statins.…”

“…Eligibility for IPE in this study was relatively higher than reported in other studies partly because the 2019 statement from the National Lipid Association did not include LDL-C criteria. Overall, the study underscored that use of lipid-lowering therapies is suboptimal ( 59 ).…”

Genetically proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations

“… 1 Proprotein convertase subtilisin–kexin type 9 ( PCSK9 )-inhibiting therapies, including monoclonal antibodies (mAb) and silencing RNA therapies (siRNA), can achieve profound, long-lasting reductions in LDL. Based on current guidelines, as many as 4% of the adult population are eligible for PCSK9 mAb therapies, 2 and this is set to increase with progressively lower treatment targets. Recently, the Food and Drug Administration expanded their remit by approving their use for familial hypercholesterolaemia down to age 10.…”