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Chapter 33: Drug Therapy for Dyslipidemias

Holly E. Gurgle; Donald K. Blumenthal

INTRODUCTION

Dyslipidemia is a major cause of ASCVDs, such as CHD, ischemic cerebrovascular disease, and peripheral vascular disease. Cardiovascular disease represents the number one cause of death among adults in many developed nations (Mozaffarian et al., 2015). Both genetic disorders and lifestyle contribute to the dyslipidemias, including hypercholesterolemia and low levels of HDL-C.

Classes of drugs that modify cholesterol levels include the following:

  • Inhibitors of HMG-CoA reductase (statins)

  • Bile acid–binding resins

  • Nicotinic acid (niacin)

  • Fibric acid derivatives (fibrates)

  • Inhibitor of cholesterol absorption (ezetimibe)

  • Omega-3 fatty acid ethyl esters (fish oil)

  • PCSK9 inhibitors

  • MTP inhibitor (lomitapide)

  • Inhibitor of apolipoprotein B-100 synthesis (mipomersen)

The 2014 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Stone et al., 2014) recommends a substantial shift in approach to cholesterol management compared to the ATPIII (Grundy et al., 2004; NCEP, 2002). Whereas ATPIII advocated treating to specific lipoprotein targets, the 2014 ACC/AHA guideline focuses on offering fixed doses of statins to patients in four statin benefit groups to reduce morbidity and mortality. Since the 2014 release of the ACC/AHA guideline, several additional expert consensus recommendations have been published, providing alternative opinions on cholesterol management (Jacobson et al., 2015) and recommendations regarding the role of nonstatin cholesterol treatments (Lloyd-Jones et al., 2016) in reduction of ASCVD risk (see Table 33–1).

Table 33–1Comparison of Key Clinical Guidelines for The Management of Cholesterol in Adults
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Table 33–1 Comparison of Key Clinical Guidelines for The Management of Cholesterol in Adults
ATPIII 2004 ACC/AHA 2014 NLA 2015 USPSTF 2016
Risk assessment strategy 10-year FRS; CHD risk factors 10-year PCE ASCVD risk factors used; FRS, PCE, or other 10-year PCE
Candidates for treatment Patients above LDL goal Patients in four statin benefit groups Patients above LDL goal Primary prevention in patients with risk
Recommended statin intensity Titrated to achieve LDL goal Moderate-to-high intensity Titrated to achieve LDL goal Low-to-moderate intensity
Recommendations

Risk groups and LDL goals:

  • High risk (LDL goal < 100, < 70 optional) if CHD, risk equivalent, or FRS ≥ 20%

  • Moderate-high risk (LDL goal < 130, < 100 optional) if ≥ 2 risk factors or FRS 10% to < 20%

  • Moderate risk (LDL goal <130, therapy started if LDL >160) if ≥2 risk factors or FRS <10%

  • Lower risk (LDL goal <160, therapy started if LDL >190) if 0 or 1 risk factor

Four statin benefit groups:

  • If ≥ 21 years old, clinical ASCVD, high-intensity statin (or moderate if > 75 years old)

  • If ≥ 21 years old and LDL ≥ 190, high-intensity statin

  • 40–75 years old with DM and LDL 70–189, moderate intensity (or high intensity if ASCVD ≥ 7.5%)

  • 40–75 years old with LDL 70–189, moderate-to-high intensity if ...

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