Martha Gulati, MD MS FACC FAHA FASPC FESC

A Look Into the Future of LDL-C Management Post ACS

As the discussion turns to the future of lipid management, the importance of outcomes data, such as the anticipated results of the ORION-4 trial, is highlighted. While lipid-lowering therapies, particularly PCSK9 inhibitors, have demonstrated their ability to reduce cardiovascular events, health systems are waiting for long-term evidence to understand how these treatments will impact patient outcomes. This data will be crucial in securing broader acceptance and integration of these therapies into routine care, particularly as health care systems demand both clinical and economic validation before making widespread changes.

Looking 5 years ahead, the panel envisions 2 main areas of progress: more targeted primary prevention and improved adherence in secondary prevention. There is a growing emphasis on personalized approaches, using advanced tools like coronary calcium scoring to identify individuals with subclinical atherosclerosis. In addition, broader population-based prevention is a key focus, with hopes for more effective trial designs that will demonstrate the long-term benefits of early intervention. A shift toward treating higher-risk individuals more aggressively is also expected, especially among those with a history of cardiovascular events.

The conversation concludes with optimism for the future. With advancements in therapy, more robust clinical evidence, and evolving health care models, there is potential to make significant strides in lipid management. A focus on prevention, along with better risk stratification and health system alignment, could lead to a health care environment where proactive care is prioritized, ensuring that patients receive the best possible outcomes while reducing the long-term costs associated with cardiovascular disease.

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Panelists discuss how the future of low-density lipoprotein cholesterol (LDL-C) management in patients with post-acute coronary syndrome (ACS) will involve more aggressive LDL-C target levels, expanded use of PCSK9 inhibitors (PCSK9i), emerging lipid-lowering therapies, personalized medicine, and the integration of lifestyle modifications and digital health tools to improve patient outcomes.

Remaining Gaps in LDL Management for High-Risk Patients

This discussion explores how implementation science is becoming the next frontier in cardiovascular prevention. Despite the wealth of clinical evidence supporting low-density lipoprotein (LDL)–lowering therapies, gaps remain in applying this knowledge consistently across the health care system. The discussion highlights that alongside biology and epidemiology, health economics and real-world utilization data are essential to building a compelling case for systemic adoption. Without demonstrating economic value, even the most effective therapies may face resistance from payers and health systems.

To overcome these barriers, the panel emphasizes the importance of reimagining care delivery. Knowlton proposes a model that incorporates clinical pharmacists into the care team to support follow-up, monitor LDL, and adjust medications. This decentralized model can relieve pressure on primary care while providing patients with consistent, expert-led care. Brown expands on this by proposing centralized, digital teams focused on lipid management—an approach proven effective at institutions like Harvard, though often challenged by sustainability and reimbursement structures.

The conversation concludes by calling out the broader need for health care reform. Prevention remains underfunded and undervalued in a system still rooted in reactive, fee-for-service care. However, as value-based care models expand, there is hope that investment in centralized preventive strategies will grow. To truly unlock this shift, the panel agrees that rigorous data demonstrating improved outcomes and cost savings is essential to convincing stakeholders to prioritize and fund preventive cardiovascular care.

Panelists discuss how research gaps in low-density lipoprotein cholesterol (LDL-C) management for high-risk populations, as highlighted by the VICTORION-INCEPTION study, include the need for long-term outcome data, combination therapy insights, and tailored approaches for diverse patient groups, alongside further investigation into safety, tolerability, and optimal LDL-C target levels.

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.

Adherence to PCSK9i

The panelists discuss how adherence to lipid-lowering therapy, particularly after acute cardiovascular events, remains one of the most significant gaps in preventive cardiology. Despite the availability of effective treatments, real-world data consistently show that a large proportion of patients fail to stay on their prescribed medications over time. In studies from integrated health systems, only about 30% to 35% of patients maintain high adherence—measured as days covered over 80%—even in the first year following an event, when the risk of recurrence is highest.

The problem doesn’t stop after the first year. Even among those who initially stay on therapy, adherence sharply declines over the next several years. This long-term drop-off has profound consequences: Patients with low adherence face significantly higher rates of adverse cardiovascular outcomes compared with those who stay on therapy consistently. These patterns hold across different low-density lipoprotein (LDL)–lowering therapies, including statins and newer agents like PCSK9 inhibitors. The issue isn’t just clinical inertia or adverse effects; it’s also psychological, educational, and systemic.

Crucially, lipid-lowering therapy isn’t a short-term fix. It’s a long-term strategy to stabilize plaque, prevent progression, and reduce the likelihood of future events. The comparison to antibiotics is misleading; cholesterol management doesn’t yield immediate symptom relief, so the motivation to persist can wane, especially if patients do not feel unwell. Addressing adherence will require a multifaceted approach: simplifying regimens, improving education, leveraging longer-acting therapies such as inclisiran, and integrating systems-based support for follow-up and prescription renewals. Until we bridge the gap between prescription and persistence, the full promise of our therapeutic arsenal will remain unrealized.

Panelists discuss how adherence to PCSK9 inhibitors (PCSK9i) can be influenced by factors such as injection frequency, cost, and patient education, with improved adherence seen when patients are supported in managing injections and provided with financial assistance.

Martha Gulati, MD MS FACC FAHA FASPC FESC

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