Treatment Strategies for Drug-Resistant Hyperlipidemia, Part 2

What side effects and risks are associated with medications for lowering LDL cholesterol? Can those risks be avoided?

Dr. Pradeep Natarajan, MD, MMSc, identifies the side effects for major LDL-C-lowering strategies as well as strategies to mitigate the risks. First-line therapies including statins and ezetimibe are discussed as well as considerations for pursuing non-statin medications such as bempodoic acid, PCSK9 mAbs, and PCSK9 siRNAs to lower LDL-C.

00:00 | Introduction
00:27 | Side effects of statin
02:50 | Minimizing statin-associated side effects
04:16 | The relationship between statins and diabetes
05:03 | Key considerations for novel non-statin agents

This video was peer reviewed by Dr. Jonathan Salik, TMD, MHPEd, Instructor of Medicine, Massachusetts General Hospital; and Dr. Sugantha Sundar, MD, Assistant Professor of Anesthesia, Beth Israel Deaconess Medical Center, to validate the quality and accuracy of the content.

References:
Wasan KM, Brocks DR, Lee SD, Sachs-Barrable K, Thornton SJ. Impact of lipoproteins on the biological activity and disposition of hydrophobic drugs: implications for drug discovery. Nat Rev Drug Discov. 2008;7(1):84-99. doi:10.1038/nrd2353

Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, et al. Major lipids, apolipoproteins and risk of vascular disease. JAMA. 2009;302(18):1993-2000. doi:10.1001/jama.2009.1619

Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459-2472. doi:10.1093/eurheartj/ehx144

Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(25):2387-2397. doi:10.1056/NEJMoa1410489

Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-1722. doi:10.1056/NEJMoa1615664

Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107. doi:10.1056/NEJMoa1801174

Goldberg AC, Leiter LA, Stroes ESG, et al. Effect of Bempedoic Acid vs. Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial [published correction appears in JAMA. 2020 Jan 21;323(3):282]. JAMA. 2019;322(18):1780-1788. doi:10.1001/jama.2019.16585

Ray KK, Wright RS, Kallend D, et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382(16):1507-1519. doi:10.1056/NEJMoa1912387

Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006;114(25):2788-2797. doi:10.1161/CIRCULATIONAHA.106.624890

Gupta A, Thompson D, Whitehouse A, et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomized, double-blind placebo-controlled trial and its non-randomized non-blind extension phase. Lancet. 2017;389(10088):2473-2481. doi:10.1016/S0140-6736(17)31075-9

Swerdlow DI, Preiss D, Kuchenbaecker KB, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomized trials. Lancet. 2015;385(9965):351-361. doi:10.1016/S0140-6736(14)61183-1

Notice: At this time, the content in this video is not accredited.