Barriers to Implementing PCSK9 Inhibitors in Clinical Practice

This segment centers on the persistent issue of medication adherence and the broader systemic barriers that prevent optimal low-density lipoprotein (LDL)–lowering therapy in high-risk patients. Even with powerful tools like inclisiran, which improves adherence through infrequent dosing, uptake remains hindered by outdated payer models and fragmented health care delivery. The conversation reframes nonadherence not as patient failure but as a consequence of misaligned incentives, limited consultation time, and administrative red tape.

The panel emphasizes that both access and persistence require structural reform. Providers face time constraints that limit patient education, while insurers enforce stepwise restrictions that delay appropriate therapy. Even when patients begin lipid-lowering regimens, long-term continuation rates drop off significantly. Data show this leads to higher event rates, underscoring that these are not short-term treatments but lifelong strategies to reduce cardiovascular risk.

To overcome these barriers, the group advocates for a paradigm shift toward prevention-focused care. Demonstrating cost-effectiveness through reduced hospitalizations and recurrent events can influence payers and policy makers. They call for trials that prove economic as well as clinical benefit, and for streamlining access through systemic changes. Ultimately, improving adherence and access will require a unified effort across patients, providers, health systems, and insurers.

Panelists discuss how barriers to implementing early PCSK9 inhibition, including financial constraints, strict clinical guidelines, patient concerns, and clinician unfamiliarity, can be overcome through strategies such as patient education, advocating for insurance support, and streamlining clinical workflows.

Alan S. Brown, MD MHA FACC FAHA MNLA

) is the third leading cause of cancer-related death despite only accounting for 3% of all new cancer diagnoses.

 Obesity is a well-known risk factor for multiple types of cancer, including PDAC. In fact, there exists a relative risk of PDAC of 1.10 for every 5-unit increment increase in body mass index (BMI).

 While bariatric surgery has been demonstrated to reduce overall cancer incidence and mortality, conflicting data exist regarding the effects of bariatric surgery on PDAC.

We performed a retrospective case-control study utilizing the National Inpatient Sample (NIS) database from October 2015 to December 2020. All adult subjects (age ≥18 years) with a BMI >40 kg/m2 or >35 kg/m2 with ≥1 metabolic comorbidity were identified and stratified into those with and without a history of bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy).

, Tenth Edition Clinical Modification (ICD-10-CM) codes were used to define variables of interest. Baseline characteristics and comorbidities among the 2 groups were compared using chi-squared and Wilcoxon rank-sum tests and logistic regression analysis was performed to assess the risk of PDAC after adjusting for multiple risk factors, including tobacco use, acute and chronic pancreatitis, diabetes mellitus and various stages of obesity.

Over 19 million subjects were included, 1,656,329 of whom had a history of bariatric surgery. Patients with a history of bariatric surgery were significantly younger, more frequently female (75% vs 58%), had higher rates of class 3 obesity (69% vs 52%) and lower prevalence of hypertension, hyperlipidemia, chronic kidney disease, Charlson Comorbidity Index (CCI) ≥3, tobacco use, acute and chronic pancreatitis and pancreatic cancer (0.1% vs 0.2%) while having a higher prevalence of OSA (

 <.001). Additionally, in-hospital mortality (0.5% vs 1.8%), total hospital charges and overall length of stay were lower in the bariatric surgery cohort compared to the nonsurgical cohort (

 <.001). After adjusting for multiple comorbidities and risk factors, history of bariatric surgery was demonstrated to significantly reduce the risk of PDAC on both univariable (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.44 - 0.56) and multivariable analysis (OR, 0.68; 95% CI, 0.61 - 0.77).

This is the largest analysis to date investigating the effects of bariatric surgery on pancreatic cancer risk reduction and serves to clarify previously inconclusive data. We have shown bariatric surgery to exhibit an independently protective effect against PDAC oncogenesis. It is reasonable to suggest that patients at increased risk of PDAC as well as other obesity-related malignancies may be recommended for surgically-assisted weight loss earlier and more frequently.

With advancements in minimally invasive bariatric procedures, expanding patient eligibility and indications for surgery, increasing utilization of bariatric surgery and endoscopic bariatric and metabolic therapies may help alleviate the growing burden of pancreatic cancer.

Surveillance, Epidemiology and End Result (SEER) Program. Surveillance Research Program, National Cancer Institute. 2023 Apr 25. https://seer.cancer.gov.

Aune D, Greenwood DC, Chan DS, et al. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol. Apr 2012;23(4):843-52. doi:10.1093/annonc/mdr398

Schauer DP, Feigelson HS, Koebnick C, et al. Bariatric Surgery and the Risk of Cancer in a Large Multisite Cohort. Ann Surg. Jan 2019;269(1):95-101. doi:10.1097/SLA.0000000000002525

Adams TD, Stroup AM, Gress RE, et al. Cancer incidence and mortality after gastric bypass surgery. Obesity (Silver Spring). Apr 2009;17(4):796-802. doi:10.1038/oby.2008.610

Sjöström L, Gummesson A, Sjöström CD, et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol. Jul 2009;10(7):653-62. doi:10.1016/S1470-2045(09)70159-7

Tee MC, Cao Y, Warnock GL, Hu FB, Chavarro JE. Effect of bariatric surgery on oncologic outcomes: a systematic review and meta-analysis. Surg Endosc. Dec 2013;27(12):4449-56. doi:10.1007/s00464-013-3127-9

Bulsei J, Chierici A, Alifano M, et al. Bariatric surgery reduces the risk of pancreatic cancer in individuals with obesity before the age of 50 years: A nationwide administrative data study in France. Eur J Surg Oncol. Apr 2023;49(4):788-793. doi:10.1016/j.ejso.2022.11.013

Fan H, Mao Q, Zhang W, Fang Q, Zou Q, Gong J. The Impact of Bariatric Surgery on Pancreatic Cancer Risk: a Systematic Review and Meta-Analysis. Obes Surg. Apr 05 2023;doi:10.1007/s11695-023-06570-x

Wilson RB, Lathigara D, Kaushal D. Systematic Review and Meta-Analysis of the Impact of Bariatric Surgery on Future Cancer Risk. Int J Mol Sci. Mar 24 2023;24(7)doi:10.3390/ijms24076192

A history of bariatric surgery was associated with up to 50% reduced risk of PDAC among a national cohort.

Bariatric Surgery is Associated with Reduced Risk of Pancreatic Cancer: Analysis of a US National Database

C. Roberto Simons-Linares, MD

Jazz Pharmaceuticals

Changing Dosage Regimens in Patients with Diabetic Macular Edema, with Mark Barakat, MD

2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting

, Mark Barakat, MD, founder and director of research at Retina Macula Institute of Arizona, presented a post-hoc analysis examining the shortening or extending of aflibercept 8 mg dosage through week 96 of the PHOTON trial.

“So here we have an agent that’s been shown to go out to not just 12, 16 weeks, but in some patients even longer, like 20 or 24 weeks,” Barakat told 

. “Right now, we’re very fortunate to have anti-VEGF agents, which really give us good results. But durability is king. So here we have something that can stretch things out longer. From a patient’s perspective, it’s a lot less injections, perhaps fewer visits.”

 were randomly assigned to aflibercept 8 mg every 12 or 16 weeks (8q12 or 8q16, respectively). After 3 monthly doses, patients were eligible for dosing modification so long as they met prespecified criteria. Dose interval shortening to a minimum 8 weeks was permitted in years 1 and 2; dose interval extension to a maximum of 24 weeks was only permitted in year 2.

Barakat and colleagues noted that dosing intervals were shortened for 12.5% and ≤16.5% of patients treated with 8q12 (n = 256) and 8q16 (n = 139) who continued until Week 96. The shortened 8q12 group exhibited best-corrected visual acuity (BCVA) at baseline and Week 96 of 61.5 and 66.9; the maintained group exhibited a 63.5 and 72 BCVA, and those extended exhibited 64.4 and 74.4 letters.

Additionally, investigators indicated that corresponding retinal thickness (CRT) was 509.1 and 333.9, 488.2 and 330.2, and 431.1 and 228.3 µm, respectively. BCVA at baseline and week 96 for the shortened, maintained, and extended subgroups was 55.4 and 62.5, 62.7 and 68.3, and 63 and 72.2 letters, respectively. Corresponding CRT was reduced from 521.5 to 341.5, 472.2 and 343.3, and 418.6 and 256 µm.

A combined 8 mg analysis revealed that baseline factors with interval shortening versus maintained or extended were shorter duration of diabetes (OR [odds ratio] .85; 95% CI, .73-1 for every 5-year increase) and thicker CRT (OR, 1.18; 95% CI, 1.07-1.31] for every 50-µm increase). Lower baseline CRT was associated with interval extension versus maintained (OR, .82; 95% CI, .74-.91 for every 50-µm increase).

Ultimately, Barakat and colleagues indicated that all dosing intervals exhibited substantial BCVA gains and CRT improvements at week 96. Patients with shorter diabetes durations or thicker CRT at baseline were more likely to have dosing intervals shortened; however, those with thinner CRT at baseline were more likely to have their dosing intervals extended.

“Frankly, apart from who gets shortened and who gets extended and maintained, the important thing is, if you look back at it, all these patients did really well in terms of anatomy and vision,” Barakat said.

Barakat reports the following disclosures: Oxurion, Janssen, RegenxBio, Novartis, Biocryst, and others.

Barakat, Mark R. Baseline characteristics and outcomes of patients treated with aflibercept 8 mg at shortened, maintained, or extended dosing intervals through 96 weeks in PHOTON. Abstract presented at Association for Research in Vision and Ophthalmology in Salt Lake City, UT, from May 3 – May 8, 2025.

A post-hoc analysis has indicated that aflibercept 8 mg has the potential to shorten or lengthen intervals between treatment in patients with DME.

Mark Barakat, MD

Marlyn Mayo, MD, is a professor of internal medicine at UT Southwestern Medical Center.

 treatment landscape was limited to just a handful of agents with limited efficacy. However, to the excitement of clinicians and patients alike, 2024 saw a major shift in PBC management with the addition of 2 new second-line therapies: elafibranor (Iqirvo) and seladelpar (Livdelzi).

The proliferator-activated receptor (PPAR) agonists earned accelerated approval from the US Food and Drug Administration in June and August, respectively. Whereas obeticholic acid used to be the only other option for patients who do not respond to or cannot tolerate first-line ursodeoxycholic acid, elafibranor and seladelpar offer long-awaited choices for patients who do not benefit from these traditional PBC therapies.

In addition to greatly expanding the PBC treatment landscape, the approvals of elafibranor and seladelpar also provide patients with treatment options that target one of the most common but underrecognized and subsequently undertreated symptoms of PBC: pruritus.

Despite studies reporting pruritus occurrence in 50-80% of PBC cases, Marlyn Mayo, MD, a professor of internal medicine at UT Southwestern Medical Center, explained to 

 how clinicians often underestimate both its prevalence and impact, as evidenced by disparities between patient-reported and physician-assessed pruritus severity. Beyond discomfort, she explained how itch has a profound effect on quality of life, contributing to sleep disturbances, fatigue, anxiety, depression, and functional impairments, including missed work and social isolation.

Marlyn Mayo, MD: Improving Pruritus Management in PBC Care

“Our traditional [PBC] therapies don't help with itch at all and may in fact make it worse,” Mayo said, describing the different guideline-recommended therapies for addressing pruritus in PBC but calling attention to the fact that none of them are universally efficacious.

However, elafibranor and seladelpar may offer viable treatment options for treating both the underlying disease as well as the itch associated with it.

“This is a really exciting time,” Mayo emphasized. “We have just had 2 new drugs approved in the US by the FDA for second-line treatment of PBC, elafibranor and seladelpar, and both of those medications seem to have a beneficial effect on pruritus… For some patients, that might be enough to treat the underlying disease as well as the itching.”

Mayo also expressed optimism about recent advancements in the development of ileal bile acid transporter (IBAT) for treating itch in PBC, with phase 3 trials nearing completion and potentially offering hope for broader application beyond their currently approved pediatric indications.

She went on to emphasize the importance of a nuanced and patient-centered approach to pruritus assessment in patients with PBC, noting the importance of moving beyond binary questioning about the presence of itching to detailed discussions of its severity, quality-of-life impacts, and patient preferences for treatment. Mayo also cites the need for early intervention with guideline-recommended pruritus-directed therapies, especially in patients with severe pruritus who cannot wait the typical 6-12 months to evaluate response to first-line treatment before initiating an itch-effective second-line option like elafibranor or seladelpar.

Editors’ note: Mayo has relevant disclosures with CymaBay, GENFIT, Gilead, GlaxoSmithKline, Ironwood, Intercept, Ipsen, and Mirum.

Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed December 9, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed December 9, 2024. 

https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis

The treatment landscape for primary biliary cholangitis (PBC) has significantly evolved with the FDA's accelerated approval of elafibranor and seladelpar as second-line therapies. These PPAR agonists offer new options for patients unresponsive to first-line ursodeoxycholic acid, addressing both the disease and pruritus, a common yet often underestimated symptom. The advancements highlight the need for a patient-centered approach to pruritus assessment and early intervention. Additionally, ongoing developments in ileal bile acid transporter therapies may further enhance treatment options for PBC-related itch.

Mayo explains current shortcomings of pruritus care in PBC and what the additions of elafibranor, seladelpar, and other agents in development may offer.

Marlyn Mayo, MD

A recent expert consensus panel—the findings of which were published in the Journal of Drugs in Dermatology—was conducted by a team of investigators who sought to provide clinical recommendations on deucravacitinib’s efficacy, safety, and appropriate laboratory monitoring in 

One of the investigators involved in the panel named Milaan Shah, MD, a Dermatology Resident at the Medical University of South Carolina in Charleston, spoke with 

’s editorial team in a recent interview. Shah was asked about the panel and some of the most notable takeaways regarding deucravacitinib and its use among patients with psoriasis.

Efficacy, Safety of Deucravacitinib for Psoriasis, with Milaan Shah, MD

“It’s a tried and true process in terms of trying to be able to combine the quantified information that's available, as well as some of those qualitative things that you see a little bit more from clinical exposure, and in the best method possible, trying to incorporate all of that,” Shah explained. “...Essentially, there were a series of articles [we reviewed] on deucravacitinib focused on treating plaque psoriasis.”

Shah described the panel, noting the comprehensive literature search of such databases as Scopus, PubMed, and Google Scholar. He highlighted the panel of 10 dermatologists with expertise in psoriasis management who reviewed the literature and crafted consensus statements using a modified Delphi process.

During the analysis, each statement by the panelists involved would be given supermajority approval and was then assigned a strength of recommendation through the use of the Strength of Recommendation Taxonomy (SORT) criteria. A total of 6 consensus statements resulted from the 14 articles selected by the investigative team.

“Of course, deucravacitinib is effective for psoriasis, but I think one of the key emphases of the panel was taking a look more at the safety profile and the adverse events associated with the medication use,” Shah said. “...That was a point of debate amongst the panel, the status of deucravacitinib within the JAK inhibitor family, given some of the TYK2 inhibitors being part of the JAK family. But in terms of side effect profile and some of the ways that it works, there are great differences within that. So we had a split, actually, halfway between the panel.”

The panelists did summarize that deucravacitinib falls under the JAK inhibitor family but highlighted the drug’s superior safety profile compared to traditional JAK inhibitors. Shah further noted that following their review of the clinical data, the panelists did not identify enough evidence of a causal role for the drug in inducing laboratory abnormalities and, therefore, did not recommend baseline and ongoing laboratory monitoring among individuals treated with deucravacitinib.

“In terms of monitoring, or triglycerides, LFTs, and things of that nature, if you look through all these, CPK levels are the one with more compelling evidence in regards to deucravacitinib potentially causing an elevation,” Shah said. “But even that was not significant. If you look through all these different phase 2 and phase 3 trials, you can see that the majority of them show that rates of those adverse events, in terms of elevations of liver enzymes, hypertriglyceridemia, CPK, and cholesterol, are about the same, if not higher or lower than placebo.”

For additional information on this panel and its findings, view Shah’s full interview posted above.

The quotes contained in this interview summary were edited for clarity.

Shah M, Burshtein J, Lebwohl M, et al. A Review of the Safety and Efficacy of Deucravacitinib for Plaque Psoriasis: An Expert Consensus Panel. J Drugs Dermatol. 2025 Feb 1;24(2):147-155. 

In this interview with Milaan Shah, MD, the expert consensus panel reviewing deucravacitinib’s safety and efficacy for psoriasis is discussed.

Milaan Shah, MD

The panel offers their final recommendations for physicians managing patients with asthma.

Advice for Clinicians Managing Asthma

S. Shahzad Mustafa, MD

Serena Fasano, MD, PhD

New Insight: The eSight Go with Roland Mattern, eSight Director of Marketing

In this episode of New Insight, host Veeral Sheth, MD, MBA, director of clinical research at University Retina and Macula Associates, speaks with Roland Mattern, director of marketing for eSight, about the development and clinical potential of the eSight Go – a fifth-generation wearable low-vision device designed to enhance central visual function in patients with conditions such as macular degeneration, diabetic retinopathy, and Stargardt’s disease.

Mattern recounted the story of eSight, which began as an engineer’s effort to help his sisters living with Stargardt’s disease. That original version evolved into a sophisticated device that uses a high-resolution camera, dual microdisplays, and proprietary software to project enhanced images onto the user’s functional retinal tissue. The eSight Go offers improved resolution, reduced lag, longer battery life, and a streamlined structure, preserving peripheral vision and optimizing cosmetic appearance.

The conversation explained the importance of mobility and independence in low-vision rehabilitation. Mattern underscored the importance of preserving peripheral vision for spatial navigation while using the enhanced central image only when needed. This hybrid approach enables users to perform daily activities, from reading and facial recognition to cooking and commuting, without relying solely on caregivers.

Sheth and Mattern explained why advanced visual aids like eSight often fall outside the awareness of retina specialists, despite high patient demand. Mattern explained eSight’s strategy to close this gap through conference presence, direct collaboration with practices, and a physician-friendly telehealth referral model. This approach includes free device trials and virtual coaching from experienced eSight Go users to help patients integrate the technology effectively and safely into their lives.

Mattern also noted the next steps for eSight and the eSight Go, highlighting scaling efforts such as clinical trials, peer education, and the expansion of a national sales force. Each of these advancements is aimed at broadening access to a device which could restore meaningful visual function and independence to patients traditionally underserved by conventional therapies.

Every episode of New Insight is available on HCPLive.com. Watch full episodes on our YouTube channel and listen wherever you get your podcasts.

Veeral Sheth, MD, is joined by the director of marketing of eSight to discuss the 5th generation eSight Go, a device to enhance central vision functions in patients with a variety of eye diseases.

Veeral Sheth, MD, MBA, FASRS, FACS

 What I’m hearing from you guys is that it’s important to educate your patients, to provide informed tools for them to make an informed decision based on their specific scenario. For our last question, I’m going to ask all of you: sickle cell disease has been around for over 100 years, and we’re still dealing with organ damage, acute exacerbations, quality-of-life issues, fatigue, difficulty finding a mate, difficulty finding work. What are your concerns around health equity and access to care that are persistent? What would be the 1 thing that if you could fix about sickle cell disease if you had a magic wand or a genie bottle? I’m going to have Dr Desai start, then Dr Shah and Dr Smith.

 I’m going to make the first wish. It’s to get every patient connected to some care—having somebody who will care and talk about these things, to say “I don’t know” sometimes and walk through life with them. We’ve talked about how complicated it is; they can’t do it by themselves. Everybody needs that advocate, they need the person that understands the disease. Even if they don’t understand, they’re willing to take that extra step. I wish everybody had a place that they could be connected to care.

 Excellent. Dr Shah, what’s your 1 wish from the genie bottle or magic wand?

 For wish No. 2, I have a 2A and 2B; they’re connected. The 2A is a big shift in mindset about therapies, from being reactive to prophylactic. We have drugs that are reactive because they’re anemic or because they have pain. But why do they have to be anemic or in pain? Why can’t we move more toward prophylactic? But because therapies are expensive, there’s so much out there, and not all patients are in centers that can give you those therapies, when we get to those therapies being prophylactic, they must be accessible, easy to take, and cost-effective. Not a drug that’s so expensive that a payer isn’t going to want to support that across the country. We have patients who aren’t plugged in to care, don’t have access to health care, and don’t have insurance. Why aren’t they getting the same therapy as another patient in an area that has a comprehensive sickle cell center? So there are 2 arms: better prophylactic medications with access to as many patients as possible.

 Public health. We don’t know how many patients have sickle cell disease in the United States, but Brazil does. Brazil is supposed to be an emerging nation. That’s a travesty. If we knew how many patients had sickle cell disease in every state in the United States, then we could more appropriately advocate for resources to do everything you just heard. We can know just by having somebody snap their finger and make each state share their newborn screening registry with each other; we could do that. Eleven states are already doing it, according to the CDC [Centers for Disease Control and Prevention]. My 1 wish is to get all 50 states to do that so we can talk intelligently about how many patients have the disease. We can then make health care allocation decisions for not just doctors but community health workers, hospitals with drugs, and community-based organizations and resources to help these patients.

 Thank you so much. My 1 wish is that all 3 of your wishes—or 3½ to 4 wishes—come true. If we get there, then each individual with sickle cell disease should be able to live to be 99 years old, get to lose all their teeth, and use a walker. Having a quality of life and a quantity of life that equals that of their peers is the ultimate goal.

I want to thank you, Dr Desai, Dr Shah, and Dr Smith. Thank you for this very informative session, for all your knowledge, and for sharing your experiences. This is a transformational period in sickle cell disease care. I look forward to more drugs being approved, I look forward to a lot more research, and I look forward to the 50 states being connected and for every patient to have access to the right type of care. Thank you very much, everyone.

Concluding their discussion on sickle cell disease management, expert panelists share key unmet needs and hopes for the future.

Authors