The Medical Letter on Drugs and Therapeutics
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ISSUE 1756
ISSUE 1756
June 8, 2026
Issue 1756
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Drugs for Hypercholesterolemia
June 8, 2026 (Issue: 1756)
Recently published multisociety guidelines for the
management of dyslipidemia emphasize early identification
and treatment of dyslipidemia to reduce the lifetime risk of
atherosclerotic cardiovascular disease (ASCVD) and death.
- AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation 2026; 153:e1154. doi:10.1161/cir.0000000000001423
- American Heart Association. The American Heart Association PREVENT online calculator. Available at https://bit.ly/4tUK3MJ. Accessed May 20, 2026.
- US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA 2022; 328:746. doi:10.1001/jama.2022.13044
- JE Blais et al. Safety and effectiveness of statins for primary prevention in adults with type 1 diabetes: an emulation. J Am Coll Cardiol 2025; 86:797. doi:10.1016/j.jacc.2025.07.013
- VKC Yan et al. Effectiveness and safety of statins in type 2 diabetes according to baseline cardiovascular risk: a target trial emulation study. Ann Intern Med 2026; 179:157. doi:10.7326/annals-25-00662
- YJ Lee et al. Intensive LDL cholesterol targeting in atherosclero-tic cardiovascular disease. N Engl J Med 2026; 394:1365. doi:10.1056/nejmoa2600283
- CP Cannon et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350:1495. doi:10.1056/nejmoa040583
- SJ Hong et al. Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized clinical trial. JAMA 2023; 329:1078. doi:10.1001/jama.2023.2487
- CB Newman et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2019; 39:e38. doi:10.1161/atv.0000000000000073
- Cholesterol Treatment Trialists' Collaboration. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet 2022; 400:832. doi:10.1016/s0140-6736(22)01545-8
- Cholesterol Treatment Trialists' (CTT) Collaboration. Effects of statin therapy on diagnosis of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes Endocrinol 2024; 12:306. doi:10.1016/s2213-8587(24)00040-8
- Cholesterol Treatment Trialists' (CTT) Collaboration. Assessment of adverse events attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials. Lancet 2026; 407:689. doi:10.1016/s0140-6736(25)01578-8
- Inhibitors and inducers of CYP enzymes, P-glycoprotein, and other transporters. Med Lett Drugs Ther 2023 January 25 (epub). Available at: medicalletter.org/downloads/CYP_PGP_Tables.pdf.
- BS Wiggins et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association. Circulation 2016; 134:e468. doi:10.1161/cir.0000000000000456
- The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011; 365:2255. doi:10.1056/nejmoa1107579
- Drug interaction: dabigatran (Pradaxa) and statins. Med Lett Drugs Ther 2017; 59:26.
- JE Jun et al. Combination of low- or moderate-intensity statin and ezetimibe vs. high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: a propensity-matched nationwide cohort study. Eur J Prev Cardiol 2024; 31:1205. doi:10.1093/eurjpc/zwae081
- Y Ouchi et al. Ezetimibe lipid-lowering trial on prevention of atherosclerotic cardiovascular disease in 75 or older (EWTOPIA 75): a randomized, controlled trial. Circulation 2019; 140:992. doi:10.1161/circulationaha.118.039415
- CP Cannon et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372:2387. doi:10.1056/nejmoa1410489
- M Banach et al. Impact of lipid-lowering combination therapy with statins and ezetimibe vs statin monotherapy on the reduction of cardiovascular outcomes: a meta-analysis. Mayo Clin Proc 2025; 100:2152. doi:10.1016/j.mayocp.2025.01.018
- Bempedoic acid (Nexletol) for lowering LDL cholesterol. Med Lett Drugs Ther 2020; 62:53.
- KK Ray et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med 2019; 380:1022. doi:10.1056/nejmoa1803917
- AC Goldberg 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. JAMA 2019; 322:1780. doi:10.1001/jama.2019.16585
- CM Ballantyne et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol 2020; 27:593. doi:10.1177/2047487319864671
- SE Nissen et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med 2023; 388:1353. doi:10.1056/nejmoa2215024
- SE Nissen et al. Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients. JAMA 2023; 330:131. doi:10.1001/jama.2023.9696
- A new indication for bempedoic acid (Nexletol). Med Lett Drugs Ther 2024; 66:75.
- F Sbrana et al. Severe HDL cholesterol reduction with bempedoic acid and fenofibrate. N Engl J Med 2025; 392:1241. doi:10.1056/nejmc2413726
- Alirocumab (Praluent) to lower LDL-cholesterol. Med Lett Drugs Ther 2015; 57:113.
- Evolocumab (Repatha) – a second PCSK9 inhibitor to lower LDLcholesterol. Med Lett Drugs Ther 2015; 57:140.
- Lerodalcibep (Lerochol) for hypercholesterolemia. Med Lett Drugs Ther 2026; 68:73.
- JG Robinson et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372:1489. doi:10.1056/nejmoa1501031
- MS Sabatine et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376:1713. doi:10.1056/nejmoa1615664
- EQ Klug et al. Efficacy and safety of lerodalcibep in patients with or at high risk of cardiovascular disease: a randomized clinical trial. JAMA Cardiol 2024; 9:800. doi:10.1001/jamacardio.2024.1659
- D Kereiakes et al. Long term efficacy and safety of lerodalcibep in patients with atherosclerotic cardiovascular disease (LIBERATE-CVD). Atherosclerosis 2024; 395:118513. doi:10.1016/j.atherosclerosis.2024.118513
- ML O'Donoghue et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation 2022; 146:1109. doi:10.1161/circulationaha.122.061620
- SG Goodman et al. Long-term efficacy, safety, and tolerability of alirocumab in 8242 patients eligible for 3 to 5 years of placebo-controlled observation in the ODYSSEY OUTCOMES trial. J Am Heart Assoc 2023; 12:e029216. doi:10.1161/jaha.122.029216
- EA Bohula et al. Evolocumab in patients without a previous myocardial infarction or stroke. N Engl J Med 2026; 394:117. doi:10.1056/nejmoa2514428
- NA Marston et al. Evolocumab to reduce first major cardiovascular events in patients without known significant atherosclerosis and with diabetes: results from the VESALIUS-CV trial. JAMA 2026; 335:1400. doi:10.1001/jama.2026.3277
- Expanded indication for PCSK9 inhibitors. Med Lett Drugs Ther 2025; 67:201.
- A Zimerman et al. Long-term cognitive safety of achieving very low LDL cholesterol with evolocumab. NEJM Evid 2025; 4:EVIDoa2400112. doi:10.1056/evidoa2400112
- Inclisiran (Leqvio) for LDL-cholesterol lowering. Med Lett Drugs Ther 2022; 64:43.
- KK Ray et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med 2020; 382:1507. doi:10.1056/nejmoa1912387
- FJ Raal et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N Engl J Med 2020; 382:1520. doi:10.1056/nejmoa1913805
- A Agarwala et al. Dyslipidemia management in women of reproductive potential: an expert clinical consensus from the National Lipid Association. J Clin Lipidol 2024; 18:e664. doi:10.1016/j.jacl.2024.05.005
- D De Oliveira-Gomes et al. Apolipoprotein B: bridging the gap between evidence and clinical practice. Circulation 2024; 150:62. doi:10.1161/circulationaha.124.068885
- CDL Johannesen et al. Apolipoprotein B and non-HDL cholesterol better reflect residual risk than LDL cholesterol in statintreated patients. J Am Coll Cardiol 2021; 77:1439. doi:10.1016/j.jacc.2021.01.027
- Lipoprotein(a) and cardiovascular risk. Med Lett Drugs Ther 2026 (in press).
- VA Bittner et al. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome. J Am Coll Cardiol 2020; 75:133. doi:10.1016/j.jacc.2019.10.057
- KK Ray et al. Effect of inclisiran on lipids in primary prevention: the ORION-11 trial. Eur Heart J 2022; 43:5047. doi:10.1093/eurheartj/ehac615
- ML O'Donoghue et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk: insights from the FOURIER trial. Circulation 2019; 139:1483. doi:10.1161/circulationaha.118.037184
- Z Ahmad et al. Update on familial hypercholesterolemia: an expert clinical consensus from the National Lipid Association. J Clin Lipidol 2026; 20:708. doi:10.1016/j.jacl.2026.01.011
- FJ Raal et al. Inhibition of PCSK9 with evolocumab in homozy-gous familial hypercholesterolaemia (TESLA Part B): a randomised, doubleblind, placebo-controlled trial. Lancet 2015; 385:341. doi:10.1016/s0140-6736(14)61374-x
- DJ Blom et al. Efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia: the ODYSSEY HoFH trial. J Am Coll Cardiol 2020; 76:131. doi:10.1016/j.jacc.2020.05.027
- Two new drugs for homozygous familial hypercholesterolemia. Med Lett Drugs Ther 2013; 55:25.
- FJ Raal et al. Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med 2020; 383:711. doi:10.1056/nejmoa2004215
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