AUTHOR: Fred F. Ferri, MD
TABLE 1 Risk Factors for Heart Disease
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BP, Blood pressure; CHD, congenital heart disease; HDL, high-density lipoprotein cholesterol.
∗HDL cholesterol >60 mg/dl counts as a negative risk factor; its presence removes one risk factor from the total count.
TABLE 6 Drugs Affecting Lipoprotein Metabolism
Drug Class | Agents and Daily Doses | Lipid/Lipoprotein Effects | Side Effects | Contraindications |
---|---|---|---|---|
HMG-CoA reductase inhibitors (statins) | Lovastatin (10-40 mg) Pravastatin (10-80 mg) Simvastatin (5-80 mg) Fluvastatin (20-40 mg) Atorvastatin (10-80 mg) Rosuvastatin (5-40 mg) Pitavastatin (2-4 mg) | LDL↓ 20%-60% HDL↑ 5%-15% TG↓ 7%-30% | Myalgias, myositis Increased liver enzymes New-onset diabetes (with intensive therapy) Unproven concerns about memory loss | Active or chronic liver disease Pregnancy Concomitant use of certain drugs∗ |
Bile acid sequestrants | Colestipol (5-20 g) Colesevelam (2.6-3.8 g) Cholestyramine (4-16 g) | LDL↓ 15%-30% HDL↑ 3%-5% TG No change or increase | Gastrointestinal distress, constipation, drug interaction, hypertriglyceridemia Decreased absorption of fat-soluble vitamins | TG >300 mg/dl GI motility disorder |
Omega-3 fatty acids | Fish oils (4-6 g) | TG↓ 45% HDL↑ 13% | Increased bleeding time Nausea | Caution with anticoagulant therapy |
Nicotinic acid | Immediate release (niacin) (1.5-3 g) Extended release (Niaspan) (1-2 g) | LDL↓ 5%-25% HDL↑ 15%-35% TG↓ 20%-50% | Flushing Hyperglycemia Hyperuricemia (or gout) Upper GI distress Hepatotoxicity | Chronic liver disease Severe gout Diabetes Peptic ulcer disease Pregnancy/lactation |
Fibric acids | Gemfibrozil (600 mg bid) Fenofibrate (45-145 mg) | LDL↓ 5%-20% HDL↑ 10%-20% TG↓ 20%-50% | Dyspepsia Gallstones Myopathy (especially with concomitant use of gemfibrozil and statins) | Severe renal disease (dose adjustment for fenofibrate) Severe hepatic disease Caution with statins Can worsen LDL cholesterol |
Ezetimibe (cholesterol absorption inhibitor) | Ezetimibe (10 mg) | LDL↓ 18% HDL↑ 1% TG↓ 8% | Abdominal pain; myalgias | Liver disease Avoid with resins and fibrates |
GI, Gastrointestinal; HDL, high-density lipoprotein; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; LDL, low-density lipoprotein; TG, triglyceride.
∗Cyclosporine, macrolide antibiotics, various antifungal agents, and cytochrome P-450 inhibitors (fibrates and niacin should be used with appropriate caution).
Dosages of simvastatin 80 mg are no longer recommended. Potential interactions with amlodipine and ranolazine warrant doses ≤2 mg daily.
Colesevelam reduces glucose and A1c ∼0.5% and has been approved for treatment of diabetes with dyslipidemia.
Modified from The National Cholesterol Education Program, JAMA 285:2486, 2001. In Boyden TF et al: Implementing new guidelines in the management of blood cholesterol, Am J Med 127:705, 2014.
TABLE 5 Combination Therapies for LDL
Statin plus ezetimibe | Ezetimibe added to a statin may further reduce LDL by 20% or more and reduce triglycerides by 7%-13%. The combination provides equivalent LDL reduction to a fourfold increase in statin dose. Daily ezetimibe added to a low-dose statin given 2-3 times/wk can improve tolerance. Combination pills containing statin and ezetimibe are available. Most common side effects reflect those of the individual drugs. Combination ezetimibe and simvastatin has been shown to decrease cardiovascular events in patients with renal disease and acute coronary syndrome. | ||
Statin and PCSK9 inhibitors | This combination is the most effective known treatment for hypercholesterolemia. There are no known negative interactions between these two therapies. This combination reduces CHD events more than statin alone. | ||
Statin plus bile acid sequestrants | Bile acid sequestrants in combination with statins further decrease LDL from 24% to 60%.Cholestyramine and colestipol can interfere with the absorption of statins. Colesevelam does not affect statin absorption. The statin-colesevelam combination is not ideal for patients with high triglycerides but may be useful in those with type 2 diabetes mellitus because colesevelam reduces glycemia. | ||
Statin plus niacin | Adding niacin to a statin can lower LDL by 10% to 20%, in addition to beneficial effects on triglycerides. When used in combination with a statin, the maximum dose of niacin should be 2000 mg/day. This combination in subjects with already low LDL levels did not reduce CHD events. | ||
Bile acid sequestrants plus niacin | Before the availability of statins, bile acid sequestrants plus niacin were used to lower LDL in high-risk patients. The availability of colesevelam and extended-release niacin has made this combination tolerable for many patients who are unable to use statins. | ||
Ezetimibe plus bile acid sequestrants | Ezetimibe inhibits cholesterol absorption, and sequestrants enhance cholesterol excretion through conversion to bile acids. The combination can have additive effects. This combination is useful for patients who cannot take statins. |
CHD, Coronary heart disease; LDL, low-density lipoprotein; PCSK9, proprotein convertase subtilisin/kexin type 9.
From Melmed S et al: Williams textbook of endocrinology, ed 14, St Louis, 2019, Elsevier.
Background Color Denotes Class and Level of Evidence: Green = Class I (Strong) Recommendation; Yellow = Class Iia (Reasonable) Recommendation; Blue = Grade A (High) Level of Evidence; Orange = Grade B (Moderate) Level of Evidence. Ascvd, Atherosclerotic Cardiovascular Disease; Cac, Coronary Artery Calcium; LDL-C, Low-Density Lipoprotein Cholesterol.
From Goldman L, Shafer AI: Goldmans Cecil medicine, ed 26, St Louis, 2019, Elsevier.
TABLE 3 Statin Benefit Groups and Recommended Therapy
Statin Benefit Group | High Intensity | Moderate Intensity | Additional Testing |
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Clinical ASCVD | Yes | Consider | None |
Primary LDL-C >190 mg/dl | Yes | Consider | None |
Diabetes without ASCVD and 10-yr risk ≥7.5%∗ | Yes | Consider | None |
Diabetes without ASCVD and 10-yr risk <7.5%∗ | Consider | Yes | Case-by-case |
Primary prevention and 10-yr risk ≥7.5%∗ | Consider | Yes | Case-by-case |
Primary prevention and 10-yr risk <7.5%∗ | Consider | Consider | Case-by-case |
ASCVD, Atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol.
∗Based on Pooled Cohort Risk Equations.
If age >75 yr or not candidate for high intensity.
If abnormal high-sensitivity C-reactive protein, coronary artery calcium, ankle-brachial index, lifetime risk.
From Boyden TF et al: Implementing new guidelines in the management of blood cholesterol, Am J Med 127:705, 2014.
TABLE 4 High-, Moderate-, and Low-Intensity Statin Therapy∗
Statin Therapy | Daily Dose | ||
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High Intensity ↓LDL-C ≥50% | Moderate Intensity ↓LDL-C 30<50% | Low Intensity§ ↓LDL-C <30% | |
Atorvastatin | (40||)-80 mg | 10(20)mg | |
Rosuvastatin | 20(40)mg | (5)10 mg | |
Simvastatin | 20-40 mg¶ | 10 mg | |
Pravastatin | 40(80)mg | 10-20 mg | |
Lovastatin | 40 mg | 20 mg | |
Fluvastatin | 80 mg (Fluvastatin XL) | 20-40 mg | |
Fluvastatin | 40 mg∗∗ | ||
Pitavastatin | 2-4 mg | 1 mg |
FDA, U.S. Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; XL, extended-release.
∗Individual responses to statin therapy varied in randomized, controlled trials and vary in clinical practice. A less-than-average response may have a biologic basis. Statins and dosages in bold were reduced in major cardiovascular events in randomized, controlled trials. Statins and doses in italics were approved by the FDA but were not tested in randomized, controlled trials.
Daily dose decreases LDL-C levels by an average of ≥50%.
Daily dose decreases LDL-C levels by an average of 30 to <50%.
§ Daily dose decreases LDL-C levels by an average of <30%.
|| Evidence from 1 randomized, controlled trial only; down-titration if patient is unable to tolerate atorvastatin, 80 mg.
¶ Although simvastatin, 80 mg, was evaluated in randomized, controlled trials, the FDA recommends against initiation of or titration to 80 mg of simvastatin because of increased risk for myopathy and rhabdomyolysis.
Reprinted with permission of the authors: Stone NJ 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 63(25, Part B):2889-2934, 2014.
Figure 1 Initiating statin therapy in individuals with clinical ASCVD.
∗Fasting lipid panel is preferred. In a nonfasting individual, a nonfasting non-HDL-C >220 mg/dl may indicate genetic hypercholesterolemia that requires further evaluation or a secondary etiology. If nonfasting triglycerides are >500 mg/dl, a fasting lipid panel is required.It is reasonable to evaluate the potential for ASCVD benefits and for adverse effects and to consider patient preferences in initiating or continuing a moderate- or high-intensity statin in individuals with ASCVD >75 yr of age. ALT, Alanine transaminase; ASCVD, atherosclerotic cardiovascular disease; CK, creatine kinase; FH, familial hypercholesterolemia; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ULN, upper limit of normal.
Modified from Stone NJ 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, 2013. In Mann DL et al: Braunwalds heart disease, ed 10, Philadelphia, 2015, Elsevier.
BOX 1 2013 ACC/AHA Summary of Key Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults
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ABI, Ankle brachial index; ACC, American College of Cardiology; AHA, American Heart Association; ALT, alanine transaminase; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CK, creatine kinase; hs-CRP, high sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; NYHA, New York Heart Association; RCTs, randomized clinical trials; TIA, transient ischemic attack.From 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 63(25 Pt B):2889-2934, 2014.
Patients with rare lipid disorders, hyperlipoproteinemias, patients resistant to treatment, on complex regimens, and with evidence of disease progression despite treatment should be referred to a lipid specialist.
∗Clinical ASCVD includes acute coronary syndromes, history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin.
These factors may include primary LDL-C of 160 mg/dl or greater or other evidence of genetic hyperlipidemias; family history of premature ASCVD with onset at less than 55 yr of age in a first-degree male relative or at less than 65 yr of age in a first-degree female relative; hs-CRP 2 mg/L or greater; CAC score 300 Agatston units or greater or 75th percentile or greater for age, sex, and ethnicity; ABI less than 0.9; or lifetime risk of ASCVD. Additional factors that might aid in individual risk assessment could be identified in the future.
§ High-risk individuals include those with clinical ASCVD, an untreated LDL-C 190 mg/dl or greater, suggesting genetic hypercholesterolemia, or individuals with diabetes 40 to 75 yr of age and LDL-C 70 to 189 mg/dl.
High Cholesterol (Patient Information)
Coronary Artery Disease (Related Key Topic)
Hyperlipoproteinemia, Primary (Related Key Topic)
Statin-Induced Muscle Syndrome (Related Key Topic)