Lowering Cholesterol Case Studies

Case 1: ω-3 Fatty Acids

Q: TZ, a 52-year-old woman with borderline-high triglyceride levels, wants to purchase supplements of ω-3 fatty acids. Her primary care physician had suggested that she increase her intake of these compounds by eating more fish, but TZ dislikes seafood. What should the pharmacist recommend?

A: Very long-chain polyunsaturatedfatty acids like docosahexaenoic (DHA) and eicosapentaenoic (EPA) reduce triglyceride levels.¹ Seafood and fatty fish are good sources of DHA and EPA, and the American Heart Association advises consuming 2 or 3 weekly servings of such foods to reduce cardiovascular risk.² However, the omega-3 fatty acid intake recommended for patients who need to lower triglycerides is 2 to 4 g per day, which can be difficult to achieve with diet alone. Fish oil supplements contain varying amounts of DHA and EPA and can lower triglyceride levels by 25% to 34%.³

Something to consider with fish oil supplements—particularly DHA—is that in high doses they may increase low-density lipoprotein (LDL) cholesterol. Products containing only EPA do not affect LDL.³ In addition to recommending EPA-only supplements awarded the United States Pharmacopeia symbol of quality assurance, the pharmacist should advise TZ to consume flaxseed, almonds, hazelnuts, pecans, or peanuts, all of which are rich in omega-3s.

Case 2: Garlic

Q: HY is a 47-year-old man seeking advice about garlic supplements for high cholesterol. He has hypercholesterolemia and hypertension and is scheduled for oral surgery in a month. HY takes 40 mg of atorvastatin and 10 mg of lisinopril daily. A relative told him that garlic can lower cholesterol and is good for heart health. What should the pharmacist recommend?

A: Garlic supplements may reduce low-density lipoprotein (LDL) and total cholesterol, but study results are contradictory. Data from a meta-analysis of 39 trials showed that garlic reduces LDL by 9 mg/dL and total cholesterol by 17 mg/dL in patients with total cholesterol of more than 200 mg/dL but has no notable effect on high-density lipoprotein (HDL) and triglyceride levels.⁴ Results from another meta-analysis of patients with coronary artery disease showed that those who consumed garlic had total cholesterol levels 16 mg/dL lower than those of patients on a placebo (P = .032), but there was no significant difference between garlic and placebo and effects on HDL, LDL, and triglycerides.⁵ Garlic is linked to an increased risk of bleeding. Daily garlic doses of 4 g or higher have been shown to increase prothrombin time and prolong bleeding after several weeks.⁶ AlthoughHY may derive a modest benefit from garlic, he should not begin taking supplements because of his upcoming surgery. The pharmacist should tell him to maintain a diet high in omega-3 fatty acids and low in saturated fat and undertake regular physical activity.

Case 3: Aspirin as Primary Prevention

Q: NW wants to take baby aspirin. He is 64 years old and has diabetes and hyperlipidemia, for which he takes metformin 500 mg and atorvastatin 20 mg daily. He has no prior events indicative of cardiovascular disease but had a gastrointestinal bleed 2 months ago. He is concerned about his high cholesterol and heard that baby aspirin can prevent heart attacks. What should the pharmacist recommend?

A: The decision to initiate low-dose aspirin for primary cardiovascular disease (CVD) prevention must be weighed against the risk of major bleeding. The US Preventive Services Task Force (USPSTF) recommends low-dose aspirin for adults aged 40 to 59 years with a 10-year risk of atherosclerosis heart disease of at least 10% and an increased risk of CVD.⁷ Patients with a high risk of bleeding and those unable to take low-dose aspirin every day are less likely to benefit.⁷

The USPSTF advises against the use of low-dose aspirin for primary prevention of CVD in adults 60 years and older because of the higher risk of bleeding.⁷ Similarly, the American College of Cardiology and the American Heart Association discourage low-dose aspirin use in individuals older than 70 and those who have an increased risk of bleeding.⁸ A history of gastrointestinal bleeding, bleeding at other sites, thrombocytopenia, and anticoagulant or nonsteroidal anti-inflammatory drug use places adults at greater risk of bleeding.⁸. Because NW is 64 years old and has experienced gastrointestinal bleeding, he is not a candidate for primary prevention with low-dose aspirin.

Case 4: Red Yeast Rice

Q: DP is a 49-year-old woman who wants to know about natural cholesterol-lowering products. A month ago, she was diagnosed with hypercholesterolemia and started on rosuvastatin 5 mg daily, which she recently had to discontinue because of severe muscle aches. DP prefers to avoid statin therapy altogether. She remembers seeing an online article about the power of red yeast rice (RYR) to reduce cholesterol levels. What should the pharmacist recommend?

A: RYR has been shown to reduce cholesterol levels. One of its ingredients, monacolin K, inhibits cholesterol production and is chemically identical to lovastatin, the first marketed pharmaceutical statin.⁹. A meta-analysis of 20 trials showed that on average RYR reduced low-density lipoprotein (LDL) cholesterol by 39.4 mg/dL compared with placebo after 2 to 24 months.10 RYR doses among studies varied from 1200 to 4800 mg per day and contained 4.8 to 24 mg of monacolin K. Three of the studies compared RYR with low-intensity statins and found in similar LDL reduction in both groups (mean difference, 0.54 mg/dL).¹⁰ RYR led to minimal improvement in high-density lipoprotein and triglyceride levels, and myopathy was not observed to increase with daily monacolin K doses of 3 to 10 mg.¹¹

DP may experience some LDL-lowering benefits with RYR but should continue not to take it with statins or cytachrome P450 3A4 inhibitors because of the increased risk of myotoxicity. She should also be counseled to select a United States Pharmacopeia-certified RYR product that contains a daily monacolin K dose of 3 to 10 mg. If she starts taking RYR, DP should notify her physician.

References

1. Goldberg RB, Sabharwal AK. Fish oil in the treatment of dyslipidemia. Curr Opin Endocrinol Diabetes Obes. 2008;15(2):167-174. doi:10.1097/MED.0b013e3282f76728
2. Lichtenstein AH, Appel LJ, Vadiveloo M, et al. Dietary guidance to improve cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2021;144(23):e472-e487. doi:10.1161/CIR.0000000000001031
3. Bradberry JC, Hilleman DE. Overview of omega-3 fatty acid therapies. P T. 2013;38(11):681-691.
4. Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. 2013;71(5):282-299. doi:10.1111/nure.12012
5. Kheirmandparizi M, Keshavarz P, Nowrouzi-Sohrabi P, et al. Effects of garlic extract on lipid profile in patients with coronary artery disease: a systematic review and meta-analysis of randomized clinical trials. Int J Clin Pract. 2021;75(12):e14974. doi:10.1111/ijcp.14974
6. Woodbury A, Sniecinski R. Garlic-induced surgical bleeding: how much is too much? AA Case Rep. 2016;7(12):266-269. doi:10.1213/XAA.0000000000000403
7. US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Aspirin use to prevent cardiovascular disease: US Preventive Services Task Force recommendation statement. JAMA. 2022;327(16):1577-1584. doi:10.1001/jama.2022.4983
8. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
9. Dujovne CA. Red yeast rice preparations: are they suitable substitutions for statins? Am J Med. 2017;130(10):1148-1150. doi:10.1016/j.amjmed.2017.05.013
10. Gerards MC, Terlou RJ, Yu H, Koks CHW, Gerdes VEA. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain – a systematic review and meta-analysis. Atherosclerosis. 2015;240(2):415-423. doi:10.1016/j.atherosclerosis.2015.04.004
11. Fogacci F, Banach M, Mikhailidis DP, et al. Safety of red yeast rice supplementation: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019;143:1-16. doi:10.1016/j.phrs.2019.02.028

About the Authors

Jahnavi Yetukuri, PharmD, is a PGY-1 pharmacy resident at Atlantic Health System in Morristown, New Jersey.

Rupal Patel Mansukhani, PharmD, FAPhA, NCTTP, is a clinical associate professor of pharmacy practice and administration at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey in Piscataway, and a transitions-of-care clinical pharmacist at Morristown Medical Center.