Effect of Access to Prescribed PCSK9 Inhibitors on Cardiovascular Outcomes

Myers, Kelly D.; Farboodi, Niloofar; Mwamburi, M; Howard, William H.; Staszak, David; Gidding, Samuel S.; Baum, Sharon; Wilemon, Katherine; Rader, Daniel J.

doi:10.1161/circoutcomes.118.005404

Cited by 68 publications

(53 citation statements)

References 34 publications

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“…It is not subject to copyright under 17 USC The copyright holder for this preprint this version posted March 8, 2021. ; https://doi.org/10.1101/2021.03.08.434130 doi: bioRxiv preprint are amongst the most expensive drugs on the market. For example, even in the developed world, health insurance companies have limited access to mAb-based PCSK9 inhibitors, which resulted in an increased risk in cardiovascular events in untreated cohorts [58]. Thus, an effective vaccine-based approach could dramatically enhance the affordability and accessibility, particularly to low-resource parts of the world.…”

Section: Discussionmentioning

confidence: 99%

A VLP-based vaccine targeting ANGPTL3 lowers plasma triglycerides in mice

Fowler

Sampson

Remaley

et al. 2021

Preprint

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Elevated triglycerides (TGs) are an important risk factor for the development of coronary heart disease (CHD) and in acute pancreatitis. Angiopoietin-like proteins 3 (ANGPTL3) and 4 (ANGPTL4) are critical regulators of TG metabolism that function by inhibiting the activity of lipoprotein lipase (LPL), which is responsible for hydrolyzing triglycerides in lipoproteins into free fatty acids. Interestingly, individuals with loss-of-function mutations in ANGPTL3 and ANGPTL4 have low plasma TG levels, have a reduced risk of CHD, and are otherwise healthy. Consequently, interventions targeting ANGPTL3 and ANGPTL4 have emerged as promising new approaches for reducing elevated TGs. Here, we developed virus-like particle (VLP) based vaccines that target the LPL binding domains of ANGPTL3 and ANGPTL4. ANGPTL3 VLPs and ANGPTL4 VLPs are highly immunogenic in mice and vaccination with ANGPTL3 VLPs, but not ANGPTL4 VLPs, was associated with reduced steady state levels of TGs. Immunization with ANGPTL3 VLPs rapidly cleared circulating TG levels following an oil gavage challenge and enhanced plasma LPL activity. These data indicate that targeting ANGPTL3 by active vaccination is potential alternative to other ANGPTL3-inhibiting therapies.

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Section: Discussionmentioning

confidence: 99%

A VLP-based vaccine targeting ANGPTL3 lowers plasma triglycerides in mice

Fowler

Sampson

Remaley

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…However, high-cost is a barrier for their integration in health care systems [12,25]. On the other hand, eligible patients who are deprived of this option show increased rate of events compared to those who were actually treated [26]. In a large observational study [26], individuals in rejected and abandoned cohorts had significantly increased risk of cardiovascular events compared with those in paid cohort.…”

Section: Discussionmentioning

confidence: 99%

Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients

et al. 2020

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“…Industry responses in this area highlight a decision-making system that is perceived to be 1) onerous, 2) arbitrary, 3) opaque, and 4) focused more on restricted utilization than on following the scientific evidence to drive patient benefit. [14][15][16][17] Here, opinions from industry representatives appear to be in harmony with those from clinicians and patients in asking for multiple improvements in the processes and decision-making on insurance coverage. The HFC has called for substantially increased transparency and rationality in regard to middle-man contracts, rebates, and the legitimacy of rules driving prior authorization processes.…”

Section: Discussionmentioning

confidence: 99%

Barriers to Clinical Trial Efficiency and Patient Access: The Heart Failure Collaboratory Industry Survey

Sinha

Psotka

Fiuzat

et al. 2020

Preprint

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Aims: Clinical trial inefficiency and lack of patient access to novel therapies have been identified as key barriers to successful heart failure innovation. The Heart Failure Collaboratory (HFC) is a consortium developed to identify and address barriers to bringing drugs and devices to market. The HFC performed an electronic cross-sectional survey of key leaders within industry to collate and interpret a sample of viewpoints on these challenges. Methods and Results: From August to September 2018, self-administered survey data were electronically collected from industry partners. Group comparisons were made via Fisher's Exact or chi-square test. Respondents most commonly rated the United States Food and Drug Administration (44.2%), Health Canada (39.5%) and European Medicines Agency (32.6%) as efficient. Respondents rated the top 3 areas with the greatest opportunity for regulatory agencies to improve efficiency: 'improve usefulness of agency feedback' (48.8%); 'improved timeliness of agency responses' (41.9%); and 'pre-specification of required magnitude of clinical effect' and 'limit excessive data requirements' (32.6%). Respondents rated items of 'excessive clinical site staff workload' (55.8%), 'overly complex case report forms' (51.2%) and 'data input errors' (39.5%) as the top 3 factors influencing data quality. Respondents rated items of 'onerous prior authorization requirements' (51.2%), 'availability of decision-making rationale' (46.5%) and 'rationality of access barriers created by payers' (44.2%) as the top 3 impediments to improving patient access to approved therapies. Conclusion: This broadly distributed survey of industry respondents identified multiple specific barriers to heart failure clinical trial efficiency and patient access, which should help direct efforts toward improvement.

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Effect of Access to Prescribed PCSK9 Inhibitors on Cardiovascular Outcomes

Abstract: Supplemental Digital Content is available in the text.

Cited by 68 publications

References 34 publications

A VLP-based vaccine targeting ANGPTL3 lowers plasma triglycerides in mice

A VLP-based vaccine targeting ANGPTL3 lowers plasma triglycerides in mice

Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients

Barriers to Clinical Trial Efficiency and Patient Access: The Heart Failure Collaboratory Industry Survey

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