Ann Marie Navar, MD, PhD, is an associate professor of cardiology at the University of Texas Southwestern Medical Center.

Ann Marie Navar, MD, PhD

Advancing ASCVD Management with PCSK9 Inhibitors

In this episode, ‘Advancing ASCVD Management with PCSK9 Inhibitors,' the panelists explore the clinical evidence base for PCSK9 inhibitors, beginning with a review of outcomes trial data from FOURIER and ODYSSEY Outcomes showing 50 to 60% LDL reductions with evolocumab and alirocumab, and relative risk reductions of approximately 15% in secondary prevention, rising to 25% in the more recent VICTORION primary prevention trial. Both FOURIER and ODYSSEY Outcomes demonstrated reductions in total mortality, and safety data have consistently shown no concerning signals at very low LDL levels, including no adverse cognitive effects even at dramatically reduced LDL concentrations. The panel also highlights that PCSK9 inhibitors provide an additional 25% reduction in lipoprotein(a), with patients carrying higher baseline levels deriving greater absolute benefit, a finding now reflected in the 2026 guidelines recommending PCSK9 inhibitor consideration in high-risk secondary prevention patients with elevated lipoprotein(a).

The panelists also reference the VICTORION-INITIATE trial, which demonstrated that facilitating early initiation of inclisiran through a dedicated support team improved both adherence and overall cardiovascular risk factor management, reinforcing the value of structured implementation approaches over sequential therapy escalation.

The conversation then turns to enlicitide, an investigational oral PCSK9 inhibitor described as a macrocyclic peptide that binds to PCSK9 in serum and prevents LDL receptor degradation through the same biological mechanism as monoclonal antibodies. Data from the Coral Reef lipids trial show nearly identical LDL lowering with enlicitide compared to injectable monoclonal antibodies, with outcomes trial results from Coral Reef anticipated through 2029.

The next episode in this series, 'Safety, Tolerability, and Patient-Centered Decision-Making in ASCVD Lipid Therapy,' features the panelists advancing their conversation on ASCVD and focusing on the safety and tolerability profiles of statins, PCSK9 inhibitors, and emerging oral therapies, while examining how patient preferences, dosing frequency, and shared decision-making shape individualized treatment choices.

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Explore where ezetimibe and bempedoic acid fit for statin‑reluctant patients, lowering LDL with proven outcomes and diabetes benefits.

The Role of Non-Statin Oral Therapies in ASCVD Risk Reduction

This episode, titled 'The Role of Non-Statin Oral Therapies in ASCVD Risk Reduction,' features expert cardiologists discussing the expanding role of non-statin oral therapies in lipid management, with a particular focus on ezetimibe and bempedoic acid as viable options for both statin-intolerant and statin-reluctant patients. The panel introduces the concept of statin reluctance to describe patients who firmly decline statin therapy regardless of clinical rationale, emphasizing that clinicians must respect patient preferences and work within those boundaries rather than risk losing the patient from care entirely. Ezetimibe is highlighted as a highly versatile agent, effective as monotherapy and as an add-on to statins, with one panelist referencing the well-established principle that doubling a statin dose yields only an additional 6% LDL reduction, making the addition of ezetimibe a far more efficient strategy for further lowering. The panel also notes that individual variability in cholesterol absorption means ezetimibe's efficacy can differ substantially between patients, reinforcing the value of a trial-based approach.

The discussion further explores bempedoic acid as a statin alternative with a favorable tolerability profile and notes its additional benefit of counteracting the diabetogenic effect associated with statin use, making it a particularly attractive option in patients at risk for diabetes. The panelists reinforce that both agents are supported by clinical outcomes trial data demonstrating reductions in cardiovascular events and emphasize that LDL lowering through any validated mechanism translates into meaningful clinical benefit. The episode closes by underscoring that there are now five distinct evidence-based pathways to reduce LDL cholesterol and cardiovascular events, offering clinicians an increasingly flexible toolkit to personalize ASCVD management across a wide range of patient profiles.

In the next episode, ‘Advancing ASCVD Management with PCSK9 Inhibitors,' panelists will continue their discussion on ASCVD and highlight the robust clinical outcomes data supporting PCSK9 inhibitor use in high and very high-risk patients, while examining how emerging oral PCSK9 inhibitors and innovative trial designs are poised to further transform the lipid-lowering treatment landscape.

Optimizing ASCVD Prevention Through Combination Therapy and Managing Statin Intolerance

In 'Optimizing ASCVD Prevention Through Combination Therapy and Managing Statin Intolerance,' our experts delve into the evolving lipid-lowering treatment landscape and how the availability of newer therapies is reshaping clinical decision-making for high and very high-risk patients. The panel describes an approach that begins with statin initiation while proactively counseling patients that monotherapy alone may be insufficient to reach LDL targets of less than 55 mg/dL or less than 70 mg/dL, depending on risk category. Ezetimibe is highlighted as an accessible, well-tolerated, and cost-effective oral add-on therapy that typically represents the logical next step, with PCSK9 inhibitors and other emerging agents available for patients who remain significantly above goal. The panelists emphasize the importance of continued lipid panel monitoring to guide sequential escalation rather than delaying combination therapy.

The discussion then turns to statin intolerance, with the panel distinguishing between patients who have clearly failed multiple statin trials and those experiencing manageable or context-dependent side effects such as exercise-related muscle complaints. For confirmed statin-intolerant patients, the panel supports moving directly to alternative therapies, while also exploring the potential to reintroduce very low dose or alternate-day statin regimens alongside other agents. The panelists underscore the importance of listening to patients whose quality of life is affected by perceived side effects, regardless of whether a clear physiological cause is identified. The episode closes by highlighting the pharmacological synergy of combining statins with PCSK9 inhibitors, noting that statins upregulate LDL receptors while PCSK9 inhibitors extend their lifespan, producing an additive benefit that makes combination therapy particularly powerful in patients requiring the lowest LDL targets.

Our next episode, 'The Role of Non-Statin Oral Therapies in ASCVD Risk Reduction,' further explores ASCVD, highlighting the clinical utility of ezetimibe and other non-statin oral agents as both adjunctive and alternative lipid-lowering strategies, and examining how the concept of statin reluctance is reshaping treatment sequencing for patients who are unwilling or unable to take statins.

See how coronary calcium images and risk graphs boost engagement, drive LDL-lowering choices, and help more patients reach cholesterol goals.

Driving Patient Engagement in ASCVD

In this episode, 'Driving Patient Engagement in ASCVD,' the panelists explore the powerful role that individualized risk communication and imaging tools play in motivating patients to engage with lipid-lowering therapy. The discussion opens with the use of personalized risk reduction graphs, which visually contrast a patient's likely cardiovascular trajectory if they remain untreated versus if they achieve LDL lowering, with panelists noting that no patient shown this visualization has declined treatment. The conversation places particular emphasis on coronary calcium scoring as a motivational tool, with one panelist describing how showing post-STEMI patients the residual plaque burden in their arteries beyond the treated lesion powerfully illustrates why LDL lowering remains essential. The panel also discusses how framing calcium score results in terms of age and sex-specific percentiles, rather than absolute numbers alone, helps patients understand their relative risk in a more meaningful way, and how 30-year risk projections can further reinforce the urgency of early intervention.

The panelists then address the practical achievability of current LDL goals, with one noting that with full access to available combination therapies, the proportion of very high-risk patients reaching less than 55 mg/dL could rise from roughly 10% to approximately 90%. The group acknowledges that adherence remains a significant barrier, while also welcoming the anticipated arrival of new oral combination therapies and improved access to existing agents. The episode closes on a sobering note, with the panel citing national registry data showing that the leading reason patients in the United States are not on guideline-recommended therapy is that their physician never offered it, reinforcing that awareness gaps among both patients and clinicians remain the most fundamental obstacle to closing the treatment gap in ASCVD.

The next episode in this series, 'Optimizing ASCVD Prevention Through Combination Therapy and Managing Statin Intolerance,' features the panelists advancing their conversation on ASCVD and focusing on how clinicians can strategically sequence and combine lipid-lowering therapies to achieve guideline-recommended LDL goals, while navigating the practical realities of statin intolerance in high and very high-risk patients.

Ann Marie Navar, MD, PhD

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