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Numbers to Nuance in Hyperlipidemia
From Numbers to Nuance in Hyperlipidemia: Expert Insights on Frequently Asked Questions About ASCVD Prevention and Lipid Management

Released: December 30, 2025

Laura Ross
Laura Ross, PA-C, MPAS, CLS, DipACLM, AACC
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Key Takeaways
  • There is no maximum target that patients’ LDL-C levels should be lowered to; rather, statins with or without other lipid-lowering therapies should be used to get patients as low and long as possible.
  • Ezetimibe remains the first add-on therapy to statins for most patients with hyperlipidemia, but PCSK9 inhibitors or bempedoic acid should be considered for those at very high risk for ASCVD.
  • Lp(a) should be measured at least once in adulthood for patients with hyperlipidemia.

Live educational symposiums offer a unique window into how healthcare professionals (HCPs) are integrating rapidly evolving evidence into their real-world practice. During the live event titled “ASCVD Prevention Through Individualized Pharmacologic and Supportive Care Management of Hyperlipidemia,” the questions HCP learners raised went beyond pharmacology alone and reflected a more nuanced approach to atherosclerotic cardiovascular disease (ASCVD) prevention and hyperlipidemia management. It was clear that HCPs were grappling with how to individualize risk assessment, interpret cumulative low-density lipoprotein cholesterol (LDL-C) exposure, align treatment intensity with patients’ goals, and navigate increasingly complex therapeutic options. The questions highlighted in this commentary underscore the need for thoughtful clarification that can support more confident, patient-centered decision-making in hyperlipidemia care. 

Key Considerations for LDL-C–Lowering Therapies
Two recurring concerns among HCP learners were whether LDL-C could be lowered too much and if very low LDL-C levels increase bleeding risk. These questions are understandable because newer therapies allow patients to reach LDL-C levels that were once thought to be unattainable. Although infants are born with LDL-C levels far lower than what is typically considered normal, those with lifelong, genetically low LDL-C do not demonstrate excess hemorrhagic stroke or cognitive harm. Furthermore, large, randomized trials have shown that PCSK9 inhibitors—in which LDL-C levels dropped by 60% or more when used with statins—are not associated with an increased risk of intracerebral hemorrhage. For patients with ASCVD, the consistent message across the latest evidence is that lower LDL-C levels that are achieved earlier and maintained longer translate into fewer adverse cardiovascular events. In clinical practice, the more meaningful question is not how low can LDL-C go but rather how long patients have been exposed to elevated LDL-C levels before treatment begins.

Another common question asked how quickly HCPs should escalate therapy when statins alone are insufficient. In contemporary ASCVD management, prolonged and stepwise delays rarely benefit patients. When patients are taking a maximally tolerated statin and their LDL-C remains above goal, adding nonstatin therapy should be viewed as treatment optimization rather than escalation or failure. Ezetimibe remains an appropriate first add-on therapy for many patients, but early consideration of a PCSK9 inhibitor or bempedoic acid is appropriate for those at very high risk for ASCVD. The 2022 American College of Cardiology Expert Consensus Decision Pathway emphasizes achieving both a substantial percentage reduction in LDL-C as well as an absolute LDL-C threshold, particularly among those with established ASCVD. Matching treatment intensity to baseline risk is central to reducing long-term adverse cardiovascular events.

Several questions focused on inclisiran—a small interfering RNA—particularly concerns about adverse events lasting for 6 months. Answering this allows me to clarify a common misconception. Inclisiran is cleared from the bloodstream within days; what persists is the biologic effect on hepatic PCSK9 production through RNA interference. Framing the mechanism of this agent as delivering an instruction to the liver rather than remaining active in the body for months often reassures patients who are anxious about intolerance or prolonged adverse events. In practice, injection-site reactions are the most common adverse reactions patients experience and are typically mild and self-limited. For those who struggle with adherence to daily oral therapy, twice-yearly dosing with inclisiran can simplify patients’ treatment and improve their long-term LDL-C control.

Lp(a) and Other Patient Factors
The subject of lipoprotein(a), also known as “Lp(a),” generated a high volume of questions among HCP learners, particularly regarding how often to measure it and how to act when elevated results return. Current guidance supports measuring Lp(a) at least once in adulthood, as levels are genetically determined and relatively stable over time. Although lifestyle modifications do not meaningfully reduce Lp(a), an elevated value is still actionable in the clinical setting. It functions as an enhanced factor that helps explain residual ASCVD risk even when LDL-C appears well controlled. In clinical practice, identifying elevated Lp(a) justifies more aggressive hyperlipidemia therapy, careful optimization of other modifiable risk factors, and thoughtful discussions with patients about their lifetime risk for ASCVD and family screening. Even without currently available targeted therapies, Lp(a) meaningfully informs shared and clinical decision-making.

Another popular question was “When is it appropriate to deprescribe lipid-lowering therapy in older adults?” Of note, age alone should not drive this decision because patients’ functional status, comorbidity burden, and care goals matter far more. Furthermore, evidence suggests that discontinuing statins in older adults with ASCVD is associated with an early increase in adverse cardiovascular events—often occurring within the first year. For patients who remain functional and are not near end of life, continuing lipid-lowering therapy remains protective. In contrast, for those with advanced frailty and/or limited life expectancy, deprescribing statins may be appropriate and should be guided by proactive and informed conversations with patients rather than as a result of reactive clinical decision-making.

Finally, many HCPs wanted tips for having more effective conversations with patients who are frustrated, hesitant, or overwhelmed by their hyperlipidemia treatment. Language plays a critical role here. HCPs should frame nonstatin therapies as complementary rather than corrective, acknowledge patients’ concerns about adverse events or cost, and explicitly connect treatment decisions to their preferences and goals. Applying these strategies can dramatically improve treatment adherence and trust in their HCP. When patients understand that combination therapy for hyperlipidemia addresses their underlying biology rather than a personal failure, they are more likely to engage in long-term care plans.

Your Thoughts
Taken together, the questions asked in the live symposium reinforce how far hyperlipidemia management has progressed. We now have multiple effective tools to address hyperlipidemia and reduce ASCVD risk, but success depends on how thoughtfully we apply them. Lower LDL-C levels for longer remains the guiding principle but achieving this requires individualized treatment strategies, clear communication, and a genuine partnership with patients. The conversations that emerged from educational programs like this one suggest HCPs are ready to meet that challenge. 

Do you currently order tests to measure Lp(a) levels at least once in your adult patients with hyperlipidemia? You can get involved in the conversation by answering the poll question and posting a comment below.

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Do you currently order tests to measure Lp(a) levels at least once in your adult patients with hyperlipidemia?

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