Case studies on cholesterol lowering

Case 1: -3 Fatty Acids

Q: TZ, a 52-year-old female with borderline triglyceride levels, wishes to purchase -3 fatty acid supplements. Her primary care physician had suggested she increase her intake of these compounds by eating more fish, but TZ does not like seafood. What should the pharmacist advise?

A: Very long chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) reduce triglyceride levels.¹ Seafood and fatty fish are good sources of DHA and EPA, and the American Heart Association recommends consuming 2 to 3 servings of these foods a week to reduce cardiovascular risk.² However, the recommended omega-3 fatty acid intake for patients who need to lower triglycerides is 2-4 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 be aware of with fish oil supplements, especially DHA, is that in high doses they can raise 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 Seal 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 on garlic supplements for high cholesterol. He has high cholesterol and hypertension and is scheduled for oral surgery in a month. HY takes 40 mg of atorvastatin and 10 mg of lisinopril per day. A relative told him that garlic can lower cholesterol and is good for heart health. What should the pharmacist advise?

A: Garlic supplements may reduce low-density lipoprotein (LDL) and total cholesterol, but study results are contradictory. Data from a meta-analysis of 39 studies showed that garlic reduced LDL by 9 mg/dL and total cholesterol by 17 mg/dL in patients with total cholesterol greater than 200 mg/dL, but it did not noticeable effect on high-density lipoproteins. HDL) and triglyceride levels.⁴ Results from another meta-analysis of patients with coronary heart disease showed that those who consumed garlic had total cholesterol levels 16 mg/dL lower than those of patients receiving placebo (P = 0.032), but there was no 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 doses of garlic of 4 g or more have been shown to increase prothrombin time and prolong bleeding after several weeks.⁶ While HY may get a modest benefit from garlic, she is not expected to start taking supplements due to her upcoming surgery. Your pharmacist should tell you to maintain a diet rich in omega-3 fatty acids and low in saturated fat and to get regular physical activity.

Case 3: Aspirin as primary prevention

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

A: The decision to initiate low-dose aspirin for the prevention of primary cardiovascular disease (CVD) must be weighed against the risk of major bleeding. The US Preventive Services Task Force (USPSTF) recommends low-dose aspirin for adults ages 40 to 59 with a 10-year risk of atherosclerotic heart disease of at least 10% and an increased risk of CVD.⁷ Patients with a high risk of bleeding and those who cannot take low-dose aspirin every day are less likely to benefit.⁷

The USPSTF does not recommend the use of low-dose aspirin for the primary prevention of cardiovascular disease in adults 60 years of age and older due to the increased risk of bleeding.⁷ Similarly, the American College of Cardiology and the American Heart Association discourage the use of low-dose aspirin in individuals older than 70 and in those who have an increased risk of bleeding.⁸ A history of gastrointestinal bleeding, bleeding at other sites, thrombocytopenia, and use of anticoagulants or nonsteroidal anti-inflammatory drugs places adults at increased risk for bleeding.⁸. Because NW is 64 years old and has had GI bleeding, he is not a candidate for primary prevention with low-dose aspirin.

Case 4: Yeasted Red Rice

Q: DP is a 49-year-old woman who wants to learn about natural products for lowering cholesterol. A month ago she was diagnosed with hypercholesterolemia and started taking rosuvastatin 5mg per day, which she recently had to stop due to severe muscle pain. DP she prefers to avoid statin therapy altogether. She recalls seeing an article online about the power of red yeast rice (RYR) to reduce cholesterol levels. What should the pharmacist advise?

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 studies showed that, on average, RYR reduced low-density lipoprotein (LDL) cholesterol by 39.4 mg/dL compared with placebo after 2-24 months.10 RYR doses across studies ranged 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-strength statins and found similar LDL reduction in both groups (mean difference, 0. 54 mg/dL).¹⁰ RYR resulted in minimal improvement in high-density lipoprotein and triglyceride levels, and no increase in myopathy was observed 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 due to the increased risk of myotoxicity. You should also be advised to select a United States Pharmacopoeia-certified RYR product that contains a daily dose of 3 to 10 mg of monacolin K. If you start taking RYR, DP should inform your doctor.

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 guide for improving 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. Nut 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 the lipid profile in patients with coronary artery disease: a systematic review and meta-analysis of randomized clinical trials. Int J Clin Practice. 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. Use of aspirin 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 Guidelines on 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 substitutes for statins? I 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. The traditional Chinese lipid-lowering agent red yeast rice results in a significant reduction of LDL, 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 at Piscataway, and a transitional clinical pharmacist at Morristown Medical Center.