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Jennifer Phillips from Generation NP, ROXANNE SINGER-GHEORGHIU from Generation NP Commented on a Post
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Non-Statin LDL-C Treatment Options

Up to 30% of patients prescribed treatment to lower LDL-C are intolerant of statins and discontinue taking them1,2. Additionally, a large segment of the LDL-C population is not at treatment goal3. These patients require additional non-statin therapy or an entirely non-statin alternative.

When considering a non-statin therapy for your patients, whether as add-on or replacement, how important are each of the following traits: oral vs. injectable product, effect on CRP, low risk of new incident diabetes? European and US guidelines differ as do AHA/ACC and AACE/ACE; which guidelines do you follow and why?

  • from Generation NP August 17, 2022
    I also follow AHA guidelines unless there is a compelling reason not to. Statin therapy is still considered first line along with lifestyle modification and non statin orals can be considered along with.
  • from Generation NP July 22, 2022
    What about very high calcium scoring test?
    Ideas
  • from Doctor Unite July 01, 2022
    Because of the importance of statins, it is not very often that we consider non-statin therapies if a patient is high risk. However, when a non-statin is chosen, oral agents are always preferred over injectables -- for obvious reasons including needle phobia, authorization, infection, etc. Zetia and PCSK9 are examples of non-statin agents I would prefer. The JUPITER trial showed how Vitamin C can also lower CRP, as well as Krill oil, omega-3 FA, vitamin D, Mediterranean diet, low-dose aspirin, Mg, and other herbal anti-inflammatories. I follow the AHA/ACC guideline closely as it is frequently updated, reliable, and based from the US.
  • from Doctor Unite July 01, 2022
    I advice diet, exercise and low dose statin and follow up the response ,if no significant improvements advice PCSK9 and may be injectable if approved by insurance.
  • from Doctor Unite June 28, 2022
    Congratulations to my PCP colleagues, for excellent comments above! (I'm not a PCP but Doctor Unite has not yet established a separate community for my specialty, Lipidology, which is relatively new) Let me add a few corrections/additions if I may:

    1. There IS compelling evidence that statins DO increase the risk of new-onset diabetes, but the effect is modest and is NEVER a reason to avoid statin use! ALWAYS, however, we must watch for development of diabetes and prevent it with diet and lifestyle, possible switch to pitavastatin (which may prevent diabetes) and/or adding pioglitazone (best diabetes prevention), if needed. (see discussion in ATVB 2021 Nov;41(11):2798-2801. doi: 10.1161/ATVBAHA.121.316893. Epub 2021 Oct 27. PMID: 34705475)
    2. "Flush-free" niacin (niacinamide or nicotinamide) has NO lipid or CVD benefit. Immediate- or timed-release niacin DOES have such benefits, although they are both controversial and difficult to use.
    3. Fish oil as a dietary supplement (OTC fish oil is NOT available in the US) is NEVER appropriate--usually too much oxidation and saturated fat. Prescription generic Lovaza is ok but only for severely elevated TG. Prescription pure EPA (Vascepa) is proven and FDA-approved to reduce CVD, at nearly any TG elevation, always with a statin. Vascepa is endorsed by a score of guidelines and statements. Although I nearly always use generics over branded agents, in this case (only), I strongly suggest we write "DAW"/brand-only.
    4. Fenofibrate is now only for severe HTG, no longer appropriate for CVD prevention in light of the recent failure of the PROMINENT trial to achieve its primary endpoint.
    5. Chest CT for coronary calcium is inexpensive and very specific for coronary artery disease. I do this routinely for primary prevention patients over 40 years or so when the patient or I need stronger reasons to treat.
  • from Doctor Unite June 28, 2022
    When patient is intolerant to statin will lower dose of statin or prescribe pitavastatin or pravastatin , We should try to get to goal , encourage diet, when not at goal , consider add zetia, bempedoic acid or injectable pcsk-9 innhibitor
  • June 22, 2022
    First and foremost the choices need to be driven by reduction in MACE. I am still not convinced that CRP is anything we can or should be using to drive treatment decisions. Still waiting for a good, prospective study or something that is not retrospective data-dredging to convince me that statins are a causation for T2DM.
  • June 20, 2022
    Prefer to use statin as fist line agents particularly in patients with known vascular disease or diabetes. If intolerant to statins I often try very low dose Rosuvastatin 5 mg dose, Pitavastatin or Pravastatin. For additional lipid lowering I often add injectable agents in the above patients with vascular disease or diabetes. Often patients are reluctant to self inject but many of those patients are willing to go to an injection center twice per year and have Leqvio injected for them. Generally follow ACC giudelines but aim for LDL as low as possible in patients with recent cardiovascular event.
  • from PA Unite June 15, 2022
    I find that empowering a patient to choose helps ensure compliance. No matter what the study may say, if the patient is non compliant, then its meaningless. Get the patient to buy-in.
  • from Doctor Unite June 12, 2022
    I follow AHA/ACC guidelines, and I suppose it's because I'm more familiar with them. Typically, my patients are somewhat averse to injectable medications, so an oral in generally preferred add on therapy. I do not have much experience with bempedoic acid due to poor managed care coverage/out of pocket costs to patients. I have not as of yet, fortunately, had any prediabetic patients progress to diabetes with statin therapy. I seem to have a difficult enough job getting LDL to goal, so hsCRP would be an afterthought.
  • from Doctor Unite June 12, 2022
    We suold try to get to goal , increase compliance with mediations diet, when not ad goal , consider nexlizet, or inyectable pcsk-9 innhibitor
  • from Doctor Unite June 12, 2022
    Patients have to be motivated and if applicable I allow them to choose oral vs injections….AHA/AACE guidelines are preferable
  • from Generation NP June 11, 2022
    I start with lifestyle modifications. If no improvement with lifestyle modifications, i would add a statin and titrate, f needed to maximum dose tolerated and recommended. I also aded Zetia and fish oil if additional therapy needed. I would consider an endocrine and cardiology referral if needed to rule out heterozygous familial hypercholesterolemia.
  • from Doctor Unite June 11, 2022
    Delivery system is important because it will increase compliance. Zeros has offered little benefit by itself. The PCSK9 meds have shown a great improvement in lowering LDL but are expensive and injectable.
  • from Doctor Unite June 11, 2022
    I definitely agree of all the statements above especially for high risk patients and those having difficulty in attaining treatment goals. I am so happy to add zetia to achieve the desired levelsWhile patients prefer oral meds , if compliance is a problem , then injectable form is the preferred option, For prediabetic , I start with non - statins.
  • from Doctor Unite June 11, 2022
    Agree with the goals to improve all mentioned measures. I push to max tolerated statin, uses CoQ10, add Zetia and fibrate to get near goal, also uses PCSK9 when LDL-C not near v70, also uses bempodic acid to achieve LDL-C goals.
  • May 31, 2022
    Agree with the majority statements above .
    I agree that 30 % intolerance is exaggerated ! big biased factor.
    I follow guidelines., prefer to star the patient on the maximally tolerated statin ,"usually higher doses ,* it could come down to powerful statin ,moderate dose ,every other day "
    then aim especially for secondary prevention patients , for 50% cut in LDL or LDL<70 mg/dl
    I usually jump to PCSK9 inh ,despite the issues mentioned above " it is worth it"
    second option , will be to add zetia ,or other non statin "Nexilezet/nexiletol"
    agree Lipoprotein A is very helpful , to decide how aggressive ,we need to treat .
    also agree of the role of TG ,& importance of lowering
  • from Doctor Unite May 28, 2022
    Will try fast with minimum highest dose of statin as per guideline.
    If not well tolerated, will prefer PCSK9 inhibitor for better effective compliance .
  • May 27, 2022
    Guidelines generally follow the data and are updated often. Best marker to follow and treat is LDL and after high dose statin, in general, I would reach for PCSK9 unless the patient is quite phobic or poorly covered for injectables in which case Zetia is OK. Pt should obviously be followed for DM and would consider Jardiance if present.
  • from Doctor Unite May 26, 2022
    increase to highest dose of tolerated statin, add Zetia for additional lowering of LDL-C, progress to PCSK-9
  • May 26, 2022
    I follow the AHA guidelines.
    For high-risk patients or those with previous CV events and still with high LDL, I add ezetimibe. And if the goal is still not achieved: I add a PCSK9.
    Literature is limited for treatment of elevated hsCRP with Crestor 20
  • from Generation NP May 26, 2022
    PCSK9 are helpful with statin and zetia and not reaching gold
  • from Doctor Unite May 26, 2022
    I generally follow the AHA guideline. Use of high dose or maximally tolerated statin. For high-risk patients or those with previous CV events and still with high LDL, ezetimibe can be added. If still high LDL levels, adding PCSK9 inh next is a reasonable option. Discussion of pros and cons of each medication should always be done with the patient. Also take time to check patient compliance and to address other risk factors such as DM, smoking and lifestyle modification.
  • from Doctor Unite May 25, 2022
    Because of the importance of statins, it is not very often that we consider non-statin therapies if a patient is high risk. However, when a non-statin is chosen, oral agents are always preferred over injectables -- for obvious reasons including needle phobia, authorization, infection, etc. Zetia and PCSK9 are examples of non-statin agents I would prefer. The JUPITER trial showed how Vitamin C can also lower CRP, as well as Krill oil, omega-3 FA, vitamin D, Mediterranean diet, low-dose aspirin, Mg, and other herbal anti-inflammatories. I follow the AHA/ACC guideline closely as it is frequently updated, reliable, and based from the US.
  • from Doctor Unite May 25, 2022
    I think that 30 % Intolerant to Statins is a definite over estimated number as SAMPSON Trial which highlighted the NOCEBO effect as pts who were not taking statins though thinking that they were taking it had similar side effects , So I think this aspect needs to be very carefully evaluated before we embark on to the Statin Intolerant management arena , However once it has been detemined with great degree of certainity that pt is statin intolerance then the issue is are we dealing with Primary Prevention or the Secondary prevention , Secondary prevention the stakes are high and what ever guidlines you follow the aim is to get the lowest LDL possible or at least 30 percent lower than when the event took place now a days consideration given to Trigs level and recently lot of interest in Lipoprotein (a) level Every effort should be done to keep some degree of statin on board no matter what the frequency and the dosage is , Once the alternative therapies are looked at PCSK-9 inhibitors top the list and which are relatively easy to get approved in secondary prevention , Ezetemibe is always there and probably should always be there along with statins in secondary prevetion any way based on some Stellar trial results from IMPROVE-IT , Nexletol is another option , Primary Prevention you have the same options but getting PCSK-9 inhbitor approved is challenging , RIsk of Diabetes with the Statin use is at best hypothetical and no evidence for it , Checking CRP level is more of a trial issue rather than a day to day practice issue it may be a factor in starting some one on a statin but no need to check it once you are targetting the LDL levels
  • from Doctor Unite May 25, 2022
    I try to follow the AHA/ACC guidelines for cholesterol control but many patients experience side effects from the statins. Then I turn to zetia, followed by fenofibrate, non-flushing niacin,and referral to nutritionist to evaluate diet and lifestyle. Also, recommend exercises at least 3 times per week.
  • from Generation NP May 25, 2022
    I tend to either trial a different statin, or increase dose of current statun. I will also add Zetia and Vascepa for triglyceride control. There are several patients in our practice who are receiving both Repatha and an oral statin, with good results.
    Nadine King FNP-c APRN
  • from PA Unite May 25, 2022
    I usually use Zetia which is well tolerated and works. Also fish oil products. Usually oral is deferred over injectables and I try to monitor pt for DM as a rule
  • May 25, 2022
    I do follow the guidelines, the initial treatment is high intensity statins with addition of Zetia if needed. If still not at goal or statin intolerant there are other treatment options such as PCSK9 inhibitors if patients are willing to take injectable medications. I do try Bempedoic acid if they are unwilling to consider injectable medications
  • from Doctor Unite May 25, 2022
    Delivery system is important for the patient to agree to use the medication
    Outcomes data is very important
  • from Generation NP May 25, 2022
    I do follow AHA/ACC guidelines. After maximizing the dose of a high-potency statin, if LDL is not to goal, then addition of ezetimibe is recommended. Patient adherence is often an issue and management requires a good deal of patient education. For those with ASCVD still not reaching goal despite oral medication and lifestyle modification, PCSK9 inhibitor is recommended. Prior authorization through insurance or a Patient Assistance Program is typically needed.
  • May 25, 2022
    I follow AHA/ACC- reliable, trusted and written by respected KOLs.
    It is important to characterize statin intolerant as not just those that do not tolerate any statin, but also those that have symptoms on higher doses of statins (the higher doses are often the ones used in many of the landmark outcome studies that showed clinical benefit).
    Zetia is my go to 1st add on agent. It reliably lowers LDL by another 20-25%. If I have a patient whose LDL is above target on intermediate dose statin (atorva 40 or rosuva 10) I would rather add Zetia than titrate the statin further. Higher dose statin alone unlikely to get to target in this patient and more likely to get side effects at which point the patient may discontinue the med altogether.
    I frequently also will rechallenge a "statin intolerant" patient with intermittent dosing- efficacious and fairly well tolerated.
    Not a big fan of bempedoic acid so far- comes with murky issues of gout flare, tendon rupture etc.
    I have a low threshold to go to PCSK9 in patients above target on best tolerated statin dose and zetia. Incliseran looks promising and will likely use this more too.
    Obviously out of pocket cost needs to be reasonable and acceptable for injectables.
  • from Doctor Unite May 25, 2022
    I too follow US ACC/AHA GUIDELINES to determine LDL goal- intensive statin therapy is first choice. If truly not tolerated-would try Zetia But Zetia by itself is not too strong.I do use Zetia with statin too to reach LDL goal.Only then I consider other meds like Bempedoic acid or PCSK9 inhibitors-cost does become a factor then. And then non compliance.
  • from Doctor Unite May 25, 2022
    In our low income, high poverty area, choosing the least expensive (and covered on insurance) option always comes first....usually this is something like Zetia; I also use Vascepa samples a lot if triglycerides are high...if all else fails to lower lipids I refer to our specialists (who unfortunately are >1 hour away)...
  • from Endocrinologist Nation May 25, 2022
    Generally do not follow guidelines. Prefer oral to start but if a recent event or need > 50% then injectable. Do not adjust therapies related to DM risk.
  • May 24, 2022
    I too tend to follow the US ACC/AHA guidelines but always look at and take from the European guidelines which are usually slightly ahead of us. Of course, cost, frequency and route all need to be considered, as does insurance coverage. Right now Zetia and PCSK9s are in the guidelines, but inclisiran may take over a lot of the market and Nexletol may also come in as well.
  • May 24, 2022
    All of the previous points are valid. As a physician practicing in the U.S. it is easiest and most defensible to follow ACC/AHA guidelines. Most data going back decades supports use of maximally-tolerated statin, usually high intensity in high risk individuals. Zetia next as add-on has advantage of also being oral, much preferred by many patients. Then bempedoic acid, also oral. Then come the PCSK9 inhibitors, inclisiran (siRNA) or Repatha/Praluent (monoclonal Abs), injectibles and pricey. We aim for safety, tolerance, and achievement of LDL goal. But we must also consider out of pocket costs for each patient before prescribing. Your optimal drugs for a given case might break the patient's bank and may not even be filled or taken.
  • May 24, 2022
    First line would maximize statin. Then consider Zetia or Nexletol vs PCSK9I (nice to stay on oral however 2x a mo or now even 2x a yr injection doable). Effect on CRP secondary and risk of diabetes not paramount to me. I generally follow ACC/AHA.
  • May 24, 2022
    Pretty quick to go to a PCSK-9. AHA/ACC guidelines are weak compared to NLA and Esp ESC (40mg/dl). We are moving based on Fourier and Odyssey to <40 which is infrequently Observed with just statins and/or Zetia.
  • May 24, 2022
    After maximizing the dose of a high-potency statin, if LDL is not to goal, then addition of ezetimibe is recommended. For those with ASCVD still not reaching goal despite oral medication and lifestyle modification, PCSK9 inhibitor is recommended, for appropriate patients who are able to afford this treatment
  • May 24, 2022
    oral preferred because earlier they are to get approved. I follow AHA/ACC guidelienes because I live in the USA. A large number of people are not at treatment , for those patients an injectable may be an option. I do not look at CRP or prediatbetes status
  • May 24, 2022
    Almost always use a potent statin. If pt is low risk can use at very low dose.
    If hi risk, needs hi dose. If intolerance, try a lower dose or different potent statin. If still intolerant, use a moderate or low potency stain. I always try to get pts on some statin as the most clinically proven drug. Risk of DM is low so would not factor in unless it actually occurs.
    First add on in Zetia, with at least some clinical evidence.
    For pts with known CVD would have low theshold for PCSK9, and would use preferentially to Zetia. Would not use PCSK9 in lower risk patients
    Only evidence for treatment for elevated hsCRP outside of ACS is with Crestor 20.
    Follow the clinical trials and evidence more than the guidelines.
  • May 24, 2022
    Oral>injectable, effect on CRP secondary but welcome, prediabetes is an issue so I avoid high dose statin; AHA/ACC guideline preferred
  • May 24, 2022
    in general I follow AHA/ACC ( ? due to familiarity)
    my patients prefer an oral agent but more importantly hard to get authorization for injectables
    because of effect of crp I prefer rosuvastatin to atorvastatin
    in patients with borderline hgb aic i try if possible to lower statin dose ( occ use every other day rx