Dyslipidemia: A Moving Target

Sometimes, it seems that dyslipidemia is a moving target. In 2013, the American College of Cardiology (ACC) and American Heart Association (AHA) issued guidelines.¹ The new recommendation, using a 10-year risk of atherosclerotic cardiovascular disease, increased the number of Americans recommended for statin therapy. In 2016, the US Preventive Services Task Force (USPSTF) released recommendations for primary prevention statin therapy.²

The recommendations differ slightly. Today, 21.5% of adults are already on lipid-lowering therapy. Following the USPSTF recommendations, an additional 15.8% of Americans (17.1 million) between 40 and 75 would receive primary prevention. The numbers for the ACC/AHA guidelines are considerably higher; an additional 24.3% (26.4 million) of Americans would be treated. This younger population would include more people who have diabetes than those identified by the USPSTF.³ Both documents agree, however, on the levels indicating elevated cholesterol (see Table 1^2,4,).

In addition, more than 60% of American adults use complementary and alternative medicines. Several nutraceuticals are used to treat dyslipidemia. The different guidelines and home management approaches can be confusing for pharmacists and patients alike. Table 2^1,2,4,5 lists basic information about dyslipidemia screening.

Conflicting Guidelines, Common Message

The most important mandate for treatment is a baseline risk of a future cardiovascular event. One reason that guidelines differ is imprecise risk estimation tools. The most important point is this: Regardless of which approach clinicians employ, a significant proportion of Americans have dyslipidemia and remain untreated.^1,2 Finding these patients means looking for those who have 1 or more cardiovascular disease (CVD) risk factors, which in addition to dyslipidemia include diabetes, hypertension, and smoking.^1,2

Among patients with dyslipidemia, the most common problem is elevated low-density lipoprotein (LDL). The first intervention is lifestyle modification, including improved diet, increased exercise, and weight loss. Note that for every 6 pounds lost, high-density lipoprotein (HDL, increases by 1 mg/dL. Clinicians should encourage patients aged 40 to 75 years who have no CVD history, 1 or more risk factors, and a calculated 10-year CVD event risk equal to or exceeding 10% to start treatment. The standard treatment for dyslipidemia is use of low to moderate doses of a statin (Table 3¹), which effectively lowers LDL and reduces cardiovascular risk. However, more than half of patients are untreated, and among those who are treated, many do not respond completely.⁶

Statin + ? = Response

Nonresponders may need additional pharmacologic treatment. Clinicians should ensure that patients optimize adherence, lifestyle changes, and statin usage before adding a nonstatin drug.

Bile acid sequestrants (eg, cholestyramine, colestipol, and colesevelam) block intestinal bile acid reabsorption, upregulating hepatic LDL receptors to recruit circulating cholesterol for bile synthesis. They are usually used with statins or with nicotinic acid. Bile acid sequestrants are preferred in women who are pregnant or planning to become pregnant and contraindicated in patients with hypertriglyceridemia. Bloating, nausea, cramping, and constipation are common. They should be taken with food and administered 4 hours before or 1 hour after thiazides, beta-blockers, warfarin, digoxin, and thyroxine.^1,2

Ezetimibe inhibits intestinal cholesterol and phytosterol absorption, lowering LDL by 15% to 20%. Ezetimibe may create small HDL increases and mild triglyceride (TG) decreases. Clinicians may prescribe ezetimibe alone in patients intolerant to statins or add it to statins for patients nonresponsive to statins at maximum doses. Adverse effects are rare.⁷

PCSK9 inhibitors (alirocumab, andevolocumab) are subcutaneous injections given once or twice monthly that prevent PCSK9 from attaching to LDL receptors. Usually, patients’ LDL cholesterol falls by 40% to 70%. The most common adverse reactions include nasopharyngitis or upper respiratory tract infection, injection site reactions, and influenza.^8,9

Nutraceuticals

Patients also use some dietary supplements to address dyslipidemia. Fiber supplements and commercially available margarines and other products containing plant sterols (sitosterol and campesterol) or stanols may reduce LDL cholesterol by up to 10% by competitively displacing cholesterol from intestinal micelles. They have no effect on HDL or TGs.¹⁰

High-dose omega-3 fatty acids can reduce TGs. Guidelines recommend 1 to 6 gm/day eicosapentaenoic acid and docosahexaenoic acid. Some studies indicate that the anti-inflammatory dose of fish oil is 2.7 g or more daily (>9 OTC capsules). People who self-medicate with fish oil usually take 1 or 2 capsules daily, a dose insufficient for TG levels >500 mg/dL; they need prescription-strength fish oil capsules. Adverse effects include burping and diarrhea. Giving fish oil capsules with meals in divided doses may lessen the adverse effects.^11-13

End Note

Dyslipidemia is a condition with serious consequences. Patients and prescribers have many questions, and frequent review of the changing landscape can keep pharmacists up-to-date.

Jeannette Y. Wick RPH, MBA, FASCP, is an assistant director of the Office of Continuing Professional Education at the University of Connecticut School of Pharmacy.

References

• Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934. doi: 10.1016/j.jacc.2013.11.002.
• US Preventive Services Task Force. 2016 USPSTF cholesterol guidelines. healthcare.uiowa.edu/familymedicine/fpinfo/Lipid/USPSTF%20Lipid.htm. Published November 2016. Accessed October 10, 2017.
• Dixon S, Devine L, Kim S; Oklahoma State Medical Proceedings. Statin guidelines: the past, the present, and the future. http://okstatemedicalproceedings.org/index.php/OSMP/article/view/21/html_1. Accessed October 10, 2017.
• National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult TreatmentPanel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.
• Goldberg AC; Merck Manual/Professional Version. Dyslipidemia (hyperlipidemia). https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/lipid-disorders/dyslipidemia. Updated August 2015. Accessed October 10, 2017.
• Cholesterol fact sheet. CDC website. www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_cholesterol.htm. Updated April 30, 2015. Accessed September 25, 2017.
• Zetia [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc; 2002. http://merck.com/product/usa/pi_circulars/z/zetia/zetia_pi.pdf. Accessed October 23, 2017.
• Praluent [prescribing information] Bridgewater, NJ: Sanofi Aventis US LLC; 2015. accessdata.fda.gov/drugsatfda_docs/label/2015/125559Orig1s000lbledt.pdf. Accessed October 23, 2017.
• Repatha [prescribing information]. Thousand Oaks, CA: Amgen Inc; 2016. http://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/repatha/repatha_pi_hcp_english.pdf. Accessed October 23, 2017.
• Hainer R. Cholesterol-lowering supplements: what works, what doesn’t. CNN website. http://cnn.com/2009/HEALTH/08/20/cholesterol.lowering.supplements/index.html. Published August 20, 2009. Accessed October 10, 2017.
• National Center for Complementary and Integrative Health. Omega-3 supplements: in depth. http://nccih.nih.gov/health/omega3/introduction.htm. Updated July 12, 2016. Accessed October 10, 2017.
• Cleland LG, James MJ, Proudman SM. Fish oil: what the prescriber needs to know. Arthritis Res Ther. 2006;8(1):202.
• Kreijkamp-Kaspers S, McGuire T, Bedford S, et al. Your questions about complementary medicines answered: fish oil. Aust Fam Physician. 2015;44(7):469-470.