The patient is a 58-year-old man with a history of coronary artery disease including a history of myocardial infarction (MI) treated with a percutaneous coronary intervention to the proximal left anterior descending artery (LAD) 3 years ago and then a recurrent MI 9 months ago resulting in another LAD stent placement. Additionally, he has a history of hypertension, dyslipidemia (high triglycerides, low HDL-C), obesity, pre-diabetes, prior 30 pack years of smoking (now quit), obstructive sleep apnea, and a family history of premature CAD. He is referred to the lipid clinic for management of his dyslipidemia in the context of statin intolerance. He has tried several statins (atorvastatin, rosuvastatin, and pravastatin) and reported unacceptable muscle side effects each time even at the lowest approved dose. He works as a flight attendant, travels frequently, and is regularly in a foreign country for 3-4 weeks at a time. His heart rate is 65 bpm and his blood pressure is 122/76 mmHg. His most recent lipid panel shows a TC 129, TG 150, LDL-C 63, and HDL-C 36 mg/dL. His lipoprotein (a) level is 64 nmol/L. His current medications include aspirin 81 mg, clopidogrel 75 mg, metoprolol succinate 50 mg, losartan 100 mg, amlodipine 5 mg, and ezetimibe 10 mg daily. The patient reports good compliance with taking his daily oral medications. He has heard recently about the newer agents available for additional lipid-lowering, and would like to lower his risk of a future heart attack.
Using the most recent 2022 ACC Expert Consensus Decision-Making Pathway on the Role of Non-Statin Therapies, he would be recommended to achieve a 50% reduction in his LDL-C and which of the following LDL-C thresholds?
Show Answer
The correct answer is: C. LDL-C <55 mg/dL
According to the 2022 ACC Expert Consensus Decision-Making Pathway on the Role of Non-Statin Therapies, he is a secondary prevention patient at "very-high risk" because he has had 2 major ASCVD events and several high risk conditions (hypertension, prior PCI). Therefore, his his recommended LDL-C goals would be to achieve a ≥50% reduction of LDL-C and an LDL-C threshold of less than 55 mg/dL.
He has already been tried on 3 statins even at the lowest approved dose and appears to have complete statin intolerance. Thus, he would be a candidate for several potential non-statin options.
The guidelies would suggest that the addition of PCSK9 inhibition with a monoclonal antibody (mAbs) (i.e., evolocumab or alirocumab) would be the next best choice, which should confer an approximate 60% reduction in LDL-C. However, he travels frequently and it may be less convenient to transport the refrigerated PCSK9 mAbs prior to administration. Inclisiran does not require refrigeration, but it is given by subcutaneous injection at a clinic or alternative injection center (AIC) every 6 months after the baseline and 3 month dose. Inclisiran lowers LDL-C by approximately 50% and might be a good alternative for a patient with issues of medication adherence, and could be considered as an alternative to the PCSK9 mAb.
This patient might favor bempedoic acid as the choice of preference for additional oral non-statin therapies. The patient reports no difficulty with being compliant with his oral medications. By adding bempedoic acid one would expect at least an additional 22% LDL-C lowering for those not on background statin therapy which would achieve an LDL-C < 55 mg/dL.
There are no complete cardiovascular outcome trials for inclisiran yet (although on-going), and as such, evidence based options such as the PCSK9 mAbs (FOURIER and ODYSSEY trials) and bempedoic acid (CLEAR Outcomes trial) should be tried first.
This patient case quiz is part of an ACC course titled Bempedoic Acid: New Evidence Transforming the LDL-C Treatment Landscape. Educational grant support is provided by Esperion. To visit the Online Course page for the Bempedoic Acid: New Evidence Transforming the LDL-C Treatment Landscape Grant, click here.
References
Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Covington AM, DePalma SM, Minissian MB, Orringer CE, Smith SC, Waring AA and Wilkins JT. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk. Journal of the American College of Cardiology. 2022;80:1366-1418.
Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, Bays HE, Moriarty PM, Menon V, Grobbee DE, Louie MJ, Chen C-F, Li N, Bloedon L, Robinson P, Horner M, Sasiela WJ, McCluskey J, Davey D, Fajardo-Campos P, Petrovic P, Fedacko J, Zmuda W, Lukyanov Y and Nicholls SJ. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. New England Journal of Medicine. 2023;388:1353-1364.
Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby J-F, Tricoci P, White HD and Zeiher AM. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. New England Journal of Medicine. 2018;379:2097-2107.
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS and Pedersen TR. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine. 2017;376:1713-1722.
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