Reducing LDL with PCSK9 Inhibitors — The Clinical Benefit of Lipid Drugs

Everett, Brendan M.; Smith, Robert J.; Hiatt, William R.

doi:10.1056/nejmp1508120

Cited by 125 publications

(94 citation statements)

References 5 publications

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“…Skeptics, and some guideline committees, suggested further reductions in LDL-C below 70 mg/dL or >50%, achievable by high intensity statin with or without ezetimibe, would have little if any additional CVD benefit as a plateau had been reached [3][4][5]. They also expressed concern that reductions to very low LDL-C levels, such as ≤25 mg/dL, could be harmful, increasing the risk of hemorrhagic stroke, cognitive impairment, cataracts and diabetes [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Are the PCSK9 inhibitors the panacea of atherosclerosis treatment?

Stein

Turner

2017

Expert Review of Cardiovascular Therapy

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Section: Introductionmentioning

confidence: 99%

Are the PCSK9 inhibitors the panacea of atherosclerosis treatment?

Stein

Turner

2017

Expert Review of Cardiovascular Therapy

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“…of PA criteria or fields required on form, mean (min, max) † 2 (1, 9) 3 (1, 12) N/A 4 (1,12) Plan requires submission of medical records 11% 34% N/A 21% ASCVD indicates atherosclerotic cardiovascular disease; HeFH, heterozygous familial hypercholesterolemia; HIX, health insurance exchange; HoFH, homozygous familial hypercholesterolemia; N/A, not applicable; and PA, prior authorization.…”

Section: Resultsmentioning

confidence: 99%

“…Alirocumab (Praluent) was approved for the treatment of patients with heterozygous familial hypercholesterolemia (FH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C), and evolocumab (Repatha) received approval for an additional indication of homozygous FH. Both drugs have been shown to be capable of reducing LDL-C levels far below what can be achieved with statin therapy alone, 1 and a recent cardiovascular outcomes trial of evolocumab showed a significant relative risk reduction in major coronary events. 2 Given the high cost of PCSK9is, their approval raised concerns that overutilization could create a budget busting effect.…”

mentioning

confidence: 99%

Prior Authorization Requirements for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Across US Private and Public Payers

Doshi

Puckett

Parmacek

et al. 2018

Circ: Cardiovascular Quality and Outcomes

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BACKGROUND:Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are an innovative treatment option for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require further lowering of low-density lipoprotein cholesterol. However, the high costs of these agents have spurred payers to implement utilization management policies to ensure appropriate use. We examined prior authorization (PA) requirements for PCSK9is across private and public US payers. METHODS AND RESULTS:We conducted an analysis of 2016 formulary coverage and PA data from a large, proprietary database with information on policies governing >95% of Americans with prescription drug coverage (275.3 million lives) within 3872 plans across the 4 major insurance segments (commercial, health insurance exchange, Medicare, and Medicaid). The key measures included administrative PA criteria (prescriber specialty, number of criteria in PA policy or number of fields on PA form, requirements for medical record submission, reauthorization requirements) and clinical/diagnostic PA criteria (approved conditions, required laboratories or other tests, required concomitant therapy, step therapy requirements, continuation criteria) for each of 2 Food and Drug Administration-approved PCSK9is. Select measures (eg, number of PA criteria/fields, medical record submission requirements) were obtained for 2 comparator cardiometabolic drugs (ezetimibe and liraglutide). Between 82% and 97% of individuals were enrolled in plans implementing PA for PCSK9is (depending on insurance segment), and one third to two thirds of these enrollees faced PAs restricting PCSK9i prescribing to a specialist. For patients with familial hypercholesterolemia, diagnostic confirmation via genetic testing or meeting minimum clinical scores/criteria was also required. PA requirements were more extensive for PCSK9is as compared with the other cardiometabolic drugs (ie, contained 3×-11× the number of PA criteria or fields on PA forms and more frequently involved the submission of medical records as supporting documentation). CONCLUSIONS:PA requirements for PCSK9is are greater than for selected other drugs within the cardiometabolic disease area, raising concerns about whether payer policies to discourage inappropriate use may also be restricting access to these drugs in patients who need them.

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“…In the second route, surrounding PCSK9 binds to low-density lipoprotein (LDLR) receptors present on the surface of hepatocytes, causing their internalization and degradation within lysosomal vesicles [33]. This affects availability of LDLR on the cell surface and consequently concentration of LDL in plasma [31,[35][36].…”

Section: Uptake Of Ldl (Low-density Lipoprotein)mentioning

confidence: 99%

Profile of Surrounding MicroRNAs in Low Density Lipoprotein Uptake

Mes¹,

Rsdo²,

Ea³

et al. 2017

Preprint

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Abstract:The atherosclerosis, a chronic and inflammatory disease that occurs when there are high levels of low-density lipoprotein (LDL) on plasma. This important risk factor for development of cardiovascular disease (CVD) is the main cause of death worldwide. MicroRNAs have recently emerged as potential biomarkers and therapeutic target for lipid metabolism disorders. In this review, we will provide profile of surrounding miRNAs that have demonstrated being regulators of PCSK9, LDLR and APOB100 genes. Recent work has identified the mir-148, mir-128, mir-27a/b, mir-185, mir-301, mir-130 as important regulators of this pathway because they decrease supply of LDL receptors through interaction with PCSK9. Inhibition of LDLR expression cause elevation of plasma LDL levels which induces atherosclerosis. While mir-30c, mir-122, mir-34 decrease MTTP, which promotes degradation of APOB100 preventing assembly and secretion of VLDL. We conclude that, when overexpressed, mir-148a, mir128 and mir-27a/b, mir-122 and mir-34 are related to decrease in LDLR, facilitating occurrence of atherosclerosis. While mir-30 has been linked to decreased atherosclerosis. Detection of miRNAs profile could be used in the future as a biomarker for disturbs linked to c-LDL uptake and in future anti-miRNAs therapies may be used in the treatment of atherosclerosis.

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Reducing LDL with PCSK9 Inhibitors — The Clinical Benefit of Lipid Drugs

Cited by 125 publications

References 5 publications

Are the PCSK9 inhibitors the panacea of atherosclerosis treatment?

Are the PCSK9 inhibitors the panacea of atherosclerosis treatment?

Prior Authorization Requirements for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Across US Private and Public Payers

Profile of Surrounding MicroRNAs in Low Density Lipoprotein Uptake

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