This transcript has been edited for clarity.
i am dr Neil Skolnik, and today we’re talking about the 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee, Journal of the American College of Cardiology2022.
This is an important guide. We now have two new U.S. Food and Drug Administration (FDA)-approved cholesterol-lowering drugs that our patients have been seeing advertised on TV for the last 2 years, and until now there hasn’t been much consensus or guidance as to how they should be should used.
First we will talk about the new drugs, and then about the recommendations for use.
Bempedoic acid is an oral drug and inclisiran is a subcutaneous injection.
Bempedoic acid acts upstream of HMG-CoA reductase to lower LDL (low density lipoprotein) cholesterol. Importantly, unlike statins, it does not cause myalgia. Used alone, it lowers LDL by about 25%, and when added to statins, lowers LDL cholesterol by about an additional 15% over statins alone. It is available in combination with ezetimibe 10 mg and when added to a statin gives an additional 38% reduction in LDL cholesterol. This is potentially very exciting as many patients on statin monotherapy do not meet their LDL-C goals and the combination of bempedoic acid with ezetimibe represents an attractive non-injectable option for many of these patients.
Side effects of bempedoic acid include a slight increase in tendon ruptures, gout, benign prostatic hyperplasia (BPH), and atrial fibrillation (AFib). The randomized controlled trial (RCT) of bempedoic acid with cardiovascular endpoints is not expected to be completed before the end of 2022.
The other new drug is Inclisiran, a subcutaneous injection given twice a year in the office, after being given first at baseline and then at 3 months. Inclisiran inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) production at the intracellular level, in contrast to PCSK9 monoclonal antibodies (mAbs), which inhibit PCSK9 at the extracellular level. But since both work in similar ways, they cannot be used together. Inclisiran lowers LDL cholesterol by approximately 50%, a hair less than the PCSK9 mAbs. The inclisiran RCT will not appear until around 2024.
So where do these new drugs fit in?
Two places in particular. First, for patients who do not reach their LDL-C goals on maximally tolerated statin therapy, after using drugs that have been shown in randomized controlled trials to have an effect on endpoints, such as: B. ezetimibe and PCSK9 mAbs. Second place is for those individuals who cannot tolerate statins, usually due to myalgia.
Let me now turn to the recommendations for the groups recommended for LDL lowering:
The first affects patients with established atherosclerotic cardiovascular disease (ASCVD) at very high risk. A high-intensity statin is recommended. If LDL-C has not decreased by 50% or is not ≤ 55 mg/dL (note that in this group the target was changed from 70 to 55 mg/dL), then consider add-on non-statin therapy – initially ezetimibe or a PCSK9 mAb. If further lowering is required after their use, use bempedoic acid. Inclisiran can be used in place of a PCSK9 mAb when there are adherence issues or when the injectable drug cannot be taken at home.
Categories 2 and 3 have similar recommendations. These are patients with LDL cholesterol > 190 mg/dL and people aged 40-75 with diabetes. Start with a statin, either moderate or high intensity. If the patient is not responding to the statin, either ezetimibe or a PCSK9 mAb should be considered. After that, if the goal is still not met, you should consider bempedoic acid or inclisiran.
Of course, the largest category for many of us is primary prevention in individuals with LDL cholesterol levels of 70-189 mg/dL with a calculated 10-year heart risk of 7.5% to 20%. Start here with a moderate-intensity statin, aiming for a 30% to 49% reduction in LDL-C, or an LDL-C level < 100 mg/dL, and then titrate to a high-intensity statin as needed.
Well, the next bit is interesting. Guidelines do not recommend non-statin therapy for further LDL lowering in this group, even if the LDL-cholesterol goal is not met, unless there is a 10-year cardiac risk of > 20%. Then, after high-intensity statin therapy, if the patient is not achieving the goal, ezetimibe should be considered. The use of the newer drugs for additional LDL lowering is currently not recommended for primary prevention unless statins are not tolerated.
This brings us to our next category of patients: those who cannot tolerate statins. First, make sure that’s actually the case. Try two or three different statins. If the patient really cannot tolerate them, bempedoic acid is an option. In this group of patients, the combination of bempedoic acid and ezetimibe can be very useful.
The key point of these recommendations is that since the new drugs do not yet have RCT data on clinical efficacy, they should be reserved for use after use of the drugs for which RCT data are available.
This is an important and clear orientation for something that we take care of on a daily basis.
I’m Neil Skolnik and this is Medscape.
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