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1w
Addressing residual risk in ASCVD: Challenges in LDL-C management and evolving therapeutic strategies.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide. Despite the proven benefit of statins, many patients fail to achieve guideline-recommended LDL-C goals. Contributing factors include poor adherence, statin intolerance, and high baseline LDL-C levels. This gap leaves patients vulnerable to residual cardiovascular risk—driven not only by LDL-C but also by other atherogenic lipoproteins, including non-HDL-C, apoB, triglyceride-rich lipoproteins, and Lp(a).

Mechanistic insights underscore LDL-C’s central role in atherosclerosis and plaque vulnerability. The PCSK9 pathway regulates LDL receptor recycling, directly influencing LDL-C levels. Inhibiting this pathway—through currently available therapeutic strategies—has been associated with enhanced LDL clearance. Imaging studies link intensive LDL-C reduction to plaque stabilization and regression. These findings support the potential benefit of earlier, more profound LDL-C lowering in high-risk populations.

Recent guideline revisions advocate for lower LDL-C thresholds and emphasize identifying patients who may benefit from more intensive lipid-lowering approaches. Systematic risk assessment, EHR tools, and shared decision-making may help clinicians address barriers to care. Multidisciplinary collaboration remains key in optimizing adherence, education, and access.

How can healthcare professionals better identify and manage ASCVD patients with high residual cardiovascular risk despite statin therapy? What changes to clinical workflows or patient engagement strategies could support timely and intensive LDL-C management?

  • 1w
    Managing CVD pts with high residual risk factors needs a holitic approach in terms of weight , BP , Diabetes , Smoking cessation , stress management but the core management pivots around Lipid management The top priority is LDL then target of level less than 55 and if lpa is elevated then PCSK-9 inhibitors indicated once then is addressed then need to focus on Triglyderides and that needs to be less than 150 based on REDCE-IT trial and agent like Vascepa needs to used ! Hopfully with the evolving AI models we will be able to identify the at risk plaques on CT angio Dynamically for more aggresive management and CRISPR technoology may even be used for Gene deletion ! so very exciting times indeed !
  • 1w
    Add Lp(a) and Apo B to the cholesterol panel; Add Repatha/Leqvio/ ACL inhibitors to the statin when LDL is not at goal; Goal for LDL for very high risk ASCVD patients is less than 55 which is hard to achieve with statins alone. PCSK9 inhibitors do decrease Lp(a) by about 25 percent even though they are not indicated for it. Medications specifically indicated to reduce Lp(a) are still in development
  • 1w
    I think getting repatha or leqvio approved and increase the norm of prescribing from pcp will be the best step forward
  • 1mo
    More is more, here. Add Repatha or Leqvio whenever you can get one approved.
  • 1mo
    Patients with ASCVD should not only have the lipid panel check but Lp(a) and Apo B should also be checked ; I have made it a practice to check Lp(a) in all my high risk patients including those with ASCVD; If LDL is high, I have a discussion with my patients about adjusting their statin or adding PCSK9 inhibitor or ACL inhibitor; Currently there are no medications approved to lower Lp(a) , but I stress life style modifications with my patients; PCSK 9 inhibitors do lower Lp(a) by about 25 % , even though they are not indicated for it; For patients with ASCVD and high Lp(a) , I tend to start PCSK9 early
  • 1mo
    Yes, it is helpful to provide patients with different options for their medication administration. The prefilled syringe provides an easy-to-use method to inject without need for re-constitution. It provides flexibility and convenience to administer the medication in the home without needing to travel to a doctor's office or a clinic. 
  • 1mo
    Should be checking for presence of atherosclerotic disease as seen in Peripheral Vascular disease or Stroke or MI or elevated APO-B or Lipoprotein A. Also findings of atherosclerosis on CT scans (Head, Neck, Chest, Abdomen, Pelvis). Aggressive LDL targets should be sought.
  • 1mo
    Unfortunately, a lot of these decisions are based on insurance coverage for the patient. We can do our best with high intensity, statins and adding Zetia and aggressive lifestyle modification but unfortunately due to insurance coverage restraint at times we are not able to escalate therapy.
  • 1mo
    So obviously, some of the secondary risk factors like coronary calcium score, Apo, protein, etc. Also realization for the appropriate levels of LDL for primary and secondary management.

    The changes for workflow are more about easy access to those secondary treatments to get the LDL down. New indication for things like we path up for primary prevention makes that easier, but also easy access to things like the Zetia. Etc. also having EMR reminders for LDL goal
  • 1mo
    CIMT and calcium heart scans are useful in dx ASCVD and also advanced lipid panel such as CardioIQ are helpful as well. For patients not responding to therapy or not at goal of LDL 55-70 per AHA with max dose statin I would consider PCSK9, Nexletol, nexlizet and or leqvio. it's also important to note lp(a) has no official FDA approved agents currently on the market, however patients such as men with hypogonadism testosterone replacement has been proven to lower lp(a) in these individuals and also niacin can be helpful in lp(a) reduction as well. lifestyle and diet/exercise is also a big component in this management.
  • 2mo
    When a patient is seen after a cardiac event:
    • Medication review:
    • Current medications are reviewed to ensure adherence, tolerance, and appropriate dosing.
    • Goals of therapy are discussed with the patient, emphasizing the importance of LDL-C lowering in secondary prevention.
    • Laboratory follow-up:
    • A fasting lipid profile is repeated 6–8 weeks after medication adjustment or initiation to assess therapeutic response.
    • Treatment adjustment:
    • If LDL-C remains >55 mg/dL despite maximally tolerated statin therapy,
    → Ezetimibe should be added.
    • If statins are not tolerated,
    → consider alternative therapies such as ezetimibe or PCSK9 inhibitors.
    • Dose titration and combination therapy are individualized based on tolerance, risk level, and LDL-C goals.
    • Patient counseling:
    • Reinforce adherence, lifestyle modification, and regular follow-up for optimal secondary prevention outcomes.
  • 3mo
    Managing lipids in ASCVD pivots around the LDL hypothesis of lower the better and depends on at which level and therapy did the event take place and in that case additional therapy , maximal dose titration and alternative therapy needs to be considered , Lpa levels needs to be done in all these pts and if elevated need to be treated with PCSK - 9 inhibitors and ezetemibe needs to be added to all the pts in statin tolerant pts they need to be continued even others meds are added ,pts need to be counselled that LDL management is the key factor in secondary prevention as well other risk factor modifications needs to be optimally managed

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