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?
Ideas
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: 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.
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
If not well tolerated, will prefer PCSK9 inhibitor for better effective compliance .
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
Nadine King FNP-c APRN
Outcomes data is very important
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.
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.
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