Since our initial review of the oral lipid-lowering adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid (Nexletol – Esperion) in 2020, cardiovascular outcomes data in statin-intolerant patients have become available.

View the Comparison Table: Some Lipid-Lowering Drugs

The FDA has approved inclisiran (Leqvio – Novartis), a small interfering RNA (siRNA) directed to proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA, as an adjunct to diet and maximally tolerated statin therapy for subcutaneous (SC) treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Inclisiran is the first FDA-approved PCSK9-directed siRNA therapeutic agent.

A synthetic form of the protein apoaequorin is the active ingredient in the over-the-counter dietary supplement Prevagen (Quincy Bioscience), which is heavily marketed to improve memory.

The FDA has approved the oral adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid for use alone (Nexletol – Esperion) and in a fixed-dose combination with the cholesterol absorption inhibitor ezetimibe (Nexlizet) as an adjunct to diet and maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-cholesterol (LDL-C). Bempedoic acid is the first ACL inhibitor to be approved in the US.

Icosapent ethyl (Vascepa – Amarin), the ethyl ester of eicosapentaenoic acid (EPA), has been approved by the FDA for use as an adjunct to maximally tolerated statin therapy to reduce the risk of major adverse cardiovascular events in adults with hypertriglyceridemia (≥150 mg/dL) who have either established cardiovascular disease (CVD) or diabetes and ≥2 additional risk factors for CVD. It is the only omega-3 polyunsaturated fatty acid (PUFA) product to be approved in the US for this indication. Icosapent ethyl and two other omega-3 PUFA prescription products (Lovaza, Epanova), which contain both EPA and docosahexaenoic acid (DHA), were approved earlier for treatment of severe hypertriglyceridemia (≥500 mg/dL).

The lipid-lowering drug rosuvastatin is now available in a sprinkle capsule formulation (Ezallor Sprinkle – Sun Pharma). Rosuvastatin tablets (Crestor, and generics) have been available since 2003.1,2

The new formulation is being marketed specifically for residents of long-term care facilities who have difficulty swallowing. Ezallor Sprinkle capsules can be swallowed whole or opened and their contents sprinkled over applesauce or mixed with water for administration via nasogastric tube.

For those long-term care residents who still have a reasonable indication for a statin but have difficulty swallowing whole tablets, crushing generic rosuvastatin tablets would be a much less expensive option.

Expanded Table: Statins

1. Rosuvastatin – a new lipid-lowering drug. Med Lett Drugs Ther 2003; 45:81
2. Lipid-lowering drugs. Med Lett Drugs Ther 2019; 61:17.

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View the Expanded Table: Statins

Cholesterol management guidelines from the American College of Cardiology/American Heart Association Task Force have recently been published. See Table 1 for a brief summary of their recommendations.

View the Expanded Table: Lipid-Lowering Drugs

The FDA has approved the HMG-CoA reductase inhibitor (statin) pitavastatin magnesium (Zypitamag – Zydus) for use in adults with primary hyperlipidemia or mixed dyslipidemia. The FDA considers pitavastatin magnesium bioequivalent to pitavastatin calcium (Livalo), which was approved in 2009.1

Statins remain the treatment of choice for most patients who require lipid-lowering therapy. Taken as an adjunct to diet modification, increased exercise, and smoking cessation, statins can reduce the risk of primary and secondary cardiovascular events and death in patients with or at high risk for atherosclerotic cardiovascular disease.2 Even in patients at low risk for cardiovascular disease, treatment with a statin can significantly reduce the incidence of cardiovascular events.3

Controlled trials in patients with cardiovascular disease have shown that high-intensity statin therapy (defined as reducing LDL-cholesterol [LDL-C] by ≥50% on average) reduces the incidence of cardiac events, stroke, and coronary death significantly more than less intensive regimens. In one meta-analysis, each additional 1 mmol/L (39 mg/dL) reduction in LDL-C was associated with a 20% reduction in major vascular events and a 10% reduction in all-cause mortality.4 In a randomized trial in 13,054 Japanese patients with stable coronary artery disease, over a median follow-up of 3.9 years, patients taking pitavastatin calcium 4 mg daily were significantly less likely than those taking 1 mg daily to have a cardiovascular event (4.3% vs 5.4%).5

Approval of pitavastatin magnesium was based on the results of trials with pitavastatin calcium; no new efficacy trials were required. The Medical Letter's review of pitavastatin calcium concluded that recommended doses of the drug had not been shown to decrease LDL-C more than other statins with longer safety records and there was no good reason to use it. That conclusion applies to pitavastatin magnesium as well.

1. Pitavastatin (Livalo) – the seventh statin. Med Lett Drugs Ther 2010; 52:57.
2. Lipid-lowering drugs. Med Lett Drugs Ther 2016; 58:133.
3. CTT Collaboration et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380:581.
4. CTT Collaboration et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376:1670.
5. I Taguchi et al. High-dose versus low-dose pitavastatin in Japanese patients with stable coronary artery disease (REAL-CAD): a randomized superiority trial. Circulation 2018; 137:1997.

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The results of the recently published FOURIER trial have shown a reduction in cardiovascular events with addition of the PCSK9 inhibitor evolocumab (Repatha) to statin therapy in patients with atherosclerotic cardiovascular disease (ASCVD).

The results of a recently published study suggest that taking the oral direct thrombin inhibitor dabigatran etexilate (Pradaxa) with either simvastatin (Zocor, and others) or lovastatin (Altoprev, and others) increases the risk of major hemorrhage.

In our recent article on Lipid-Lowering Drugs,1 we said that statins can reduce the risk of first cardiovascular events and death (primary prevention) in patients at high risk for atherosclerotic cardiovascular disease (CVD) and significantly reduce the incidence of cardiovascular events in patients at lower risk for CVD. Now the United States Preventive Services Task Force (USPSTF) has issued new recommendations on the appropriate use of statins for primary prevention of CVD.2

The USPSTF states that clinicians should periodically screen all persons 40-75 years old for cardiovascular risk factors and evaluate their 10-year risk of CVD using the ACC/AHA Pooled Cohort Equation.3 It recommends starting low- to moderate-intensity statin therapy (lowintensity statin therapy lowers LDL-cholesterol <30%; moderate-intensity statin therapy lowers it 30-<50%) in adults 40-75 years old without CVD who have one or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of >10%. For patients with the same characteristics but a 7.5-10% 10-year risk, the USPSTF recommends that clinicians "selectively offer" the same treatment.

The new recommendations do not apply to patients with familial hypercholesterolemia or LDL-cholesterol levels ≥190 mg/dL, who should take a statin regardless of calculated risk. The USPSTF found the evidence insufficient to recommend starting a statin for primary prevention in persons >75 years old.

1. Lipid-lowering drugs. Med Lett Drugs Ther 2016; 58:133.
2. US Preventive Services Task Force et al. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 316:1997.
3. American Heart Association and American College of Cardiology. ASCVD Risk Estimator. Available at: tools.acc.org. Accessed November 22, 2016.

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Lipid-lowering drugs should be taken indefinitely; when they are stopped, plasma lipoproteins return to pretreatment levels. HMG-CoA reductase inhibitors (statins) remain the drugs of choice for treatment of most patients who require lipid-lowering therapy.

The FDA has approved the subcutaneously injected PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor alirocumab (Praluent – Sanofi/Regeneron) as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease who require additional lowering of LDL-cholesterol (LDL-C). It was not approved for general use in statin-intolerant patients. Alirocumab is the first PCSK9 inhibitor to be approved in the US. Evolocumab (Repatha – Amgen), another PCSK9 inhibitor, was recently approved in Europe and has been recommended for approval for the same indications in the US by an FDA Advisory Committee.

Combining a statin with another drug that lowers low-density lipoprotein cholesterol (LDL-C), such as colesevelam (Welchol), niacin (Niaspan, and others), or ezetimibe (Zetia), can reduce LDL-C levels more than a statin alone, but studies convincingly demonstrating that such combinations improve clinical outcomes have been lacking. The results of a long-term randomized, double-blind clinical trial (IMPROVE-IT) recently presented at the American Heart Association's Scientific Sessions 2014 indicate that addition of ezetimibe to simvastatin in high-risk patients reduces cardiovascular events.1

IMPROVE-IT compared the efficacy of simvastatin 40 mg plus placebo with that of simvastatin 40 mg plus ezetimibe 10 mg (Vytorin) in preventing the primary endpoint, a composite of cardiovascular events (cardiovascular death, MI, hospital admission for unstable angina, coronary revascularization, or stroke) in patients with acute coronary syndrome and normal LDL-C levels (≤125 mg/dL; mean 95 mg/dL). After one year, mean LDL-C was reduced further with the addition of ezetimibe (to 53.2 vs. 69.9 mg/dL with simvastatin alone). After 7 years, 2742 events had occurred among the 9077 patients taking simvastatin plus placebo and 2572 among the 9067 taking simvastatin plus ezetimibe (event rate: 34.7% vs. 32.7%; p = 0.016). There was no significant difference between the 2 groups in noncardiovascular adverse events, including gallbladder-related events, myopathy, or cancer.

1. C Cannon et al. IMProved Reduction of Outcomes: Vytorin Efficacy International Trial. Available at www.timi.org. Accessed November 21, 2014.

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In 2012, the FDA required manufacturers of HMG-CoA reductase inhibitors (statins) to add a warning to their labels about reports of increased blood glucose and glycosylated hemoglobin (HbA1c) levels. Since then, several new studies have been published.

HMG-CoA reductase inhibitors (statins) inhibit the enzyme that catalyzes the rate-limiting step in cholesterol synthesis. The subsequent reduction in hepatic cholesterol leads to increased expression of LDL receptors, which in turn increases uptake and clearance of LDL-C from the blood. Statins also lower very low-density lipoprotein cholesterol (VLDL-C) and triglycerides. Most statins increase high-density lipoprotein cholesterol (HDL-C), but only modestly.

The FDA has approved mipomersen (Kynamro – Genzyme) and lomitapide (Juxtapid – Aegerion), each in addition to a low-fat diet and other lipid-lowering medications, to reduce cholesterol levels in patients with homozygous familial hypercholesterolemia (HoFH).

Fibrates, niacin and fish oil are promoted for treatment of hypertriglyceridemia. HMG-CoA reductase inhibitors (statins) can lower elevated serum concentrations of triglycerides, but less so than fibrates, niacins or fish oil. Lifestyle changes such as weight reduction, exercise and decreasing alcohol intake can also lower serum triglyceride levels and should be tried first.

Citing some recent reports, the FDA has announced changes in the safety labeling of all HMG-CoA reductase inhibitors (statins).

The results of the AIM-HIGH trial conducted by the US National Heart, Lung and Blood Institute (NHLBI) were recently published. The goal of the trial was to test whether addition of niacin to intensive statin therapy would further reduce the risk of cardiovascular disease. The trial was stopped prematurely after an average follow-up of 3 years because niacin therapy had not shown any clinical benefit.

The FDA has approved Juvisync (Merck), a fixed-dose combination of the antihyperglycemic DPP-4 inhibitor sitagliptin (Januvia) and the HMG-CoA reductase inhibitor simvastatin (Zocor, and others).

The FDA has announced changes in the labeling of simvastatin to reduce the risk of myopathy. These changes include limiting the use of the 80-mg maximum dose to patients who have been taking it for 12 months or more without evidence of myopathy and new recommendations for use of simvastatin with other drugs. Simvastatin is available alone (Zocor, and others) and in combination with ezetimibe (Vytorin) and with niacin (Simcor).

Drugs that lower low-density lipoprotein cholesterol (LDL-C) concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions. Lipid-regulating drugs must be taken indefinitely; when they are stopped, plasma lipoproteins return to pretreatment levels in 2-3 weeks.

The FDA has approved the marketing of pitavastatin (Livalo – Kowa), an HMG-CoA reductase inhibitor (“statin”), for treatment of primary hyperlipidemia or mixed dyslipidemia. It has been available in Japan since 2003. All of the statins now available in the US are listed in the table on page 58.

Red yeast rice is a food product that has been used in Chinese cooking and medicine for centuries. It is available in the US in a capsule formulation and is often used by patients who want a "natural" product to lower cholesterol.

The National Cholesterol Education Program recommends that LDL-C be lowered to less than 100 mg/dL (2.6 mmol/L) and considers a value <70 mg/dL (1.8 mmol/L) a reasonable goal for patients at very high risk.

Modestly elevated C-reactive protein (CRP) concentrations have been associated with an increased risk of coronary heart disease. The recently published and heavily publicized results of the JUPITER trial will lead many patients to ask health care professionals whether they should have a CRP test to see if they should be taking a statin.

Advertisements for atorvastatin (Lipitor), the market leader facing generic competition, have been in the news recently in the US. Lovastatin, pravastatin and simvastatin are all available generically at a much lower retail price or lower co-pay than atorvastatin.

The FDA has approved the marketing of a second fixed-dose combination of extended-release niacin (Niaspan) with a generic statin. Niaspan/simvastatin (Simcor - Abbott) is approved for use in patients with hypercholesterolemia or mixed dyslipidemia (high LDL-cholesterol, low HDL-cholesterol and high serum triglycerides). Niaspan/lovastatin (Advicor) was marketed previously for the same indications.

Drugs that lower low-density lipoprotein cholesterol (LDL-C) concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions. They should not be used as a substitute for lifestyle changes; a combination of diet, exercise and lipid-lowering drugs is optimal for prevention of coronary disease. Lipid-regulating drugs must be taken indefinitely; when they are stopped, plasma lipoprotein levels return to pretreatment levels in 2-3 weeks.

An unpublished 2-year randomized study (ENHANCE) on the effect of adding ezetimibe 10 mg to simvastatin 80 mg in 720 patients with heterozygous familial hypercholesterolemia has been in the news recently. About 80% of these patients had previously been treated with statins. The primary endpoint was the change in the intima-media thickness (IMT) of the carotid artery (baseline 0.68 and 0.69 mm); the IMT increased by 0.0111 mm with ezetimibe plus simvastatin and 0.0058 mm with simvastatin 80 mg alone (p=0.29). The ezetimibe- simvastatin combination lowered LDL-C by 58% compared to 41% lowering with simvastatin alone (p<0.01). The study was not powered to assess cardiovascular events; cardiovascular deaths occurred in 2 patients treated with both drugs and 1 on simvastatin alone.

Ezetimibe, an inhibitor of cholesterol absorption, is available both alone (Zetia) and in combination with 10, 20, 40 and 80 mg of simvastatin (Vytorin). No data have been published on the effect of ezetimibe on cardiovascular events with or without simvastatin. Whether addition of ezetimibe to a statin is as effective as raising the dose of the statin in decreasing the number of cardiovascular events remains to be determined in larger studies that are underway.

Neither Zetia or Vytorin is recommended for initial treatment of hypercholesterolemia.

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The drugs of choice for treatment of some fungal infections are listed in the tables. Some of the indications and dosages recommended here have not been approved by the FDA. Other guidelines are available from the Infectious Diseases Society of America (www.idsociety.org).

Statins have been shown to reduce the risk of stroke in patients at high risk for cardiovascular disease (Treat Guidel Med Lett 2005; 3:15). A recent issue of The New England Journal of Medicine includes the results of a study sponsored by the manufacturer in which 80 mg of atorvastatin (Lipitor – Pfizer) or placebo was given to 4731 patients without coronary artery disease who had had a stroke or transient ischemic attack (TIA) within one to six months before study entry (The Stroke Prevention by Aggressive Reduction in Cholesterol Levels [SPARCL] Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355:549). Patients were not required to have elevated cholesterol levels to enroll. The authors conclude that the study results support starting atorvastatin treatment soon after a stroke or TIA.

The primary study endpoint was a nonfatal or fatal stroke. During a median follow-up of 4.9 years, patients treated with atorvastatin had 265 strokes compared to 307 strokes with placebo. Patients treated with atorvastatin had 56 fewer ischemic strokes and 22 more hemorrhagic strokes. They also had 39 fewer coronary events. There were 216 deaths among patients treated with atorvastatin and 211 among those treated with placebo.

Whether patients with a recent ischemic stroke or TIA would be as well protected against a recurrence and against coronary events by a lower dose of atorvastatin or by another less potent statin remains to be determined. The risk of myopathy and rhabdomyolysis with statins is dose-related; atorvastatin is the second-most potent statin on the US market (rosuvastatin is the most potent), and 80 mg is its maximum dose. Statins have an antithrombotic effect, and an increase in hemorrhagic stroke in patients with cerebrovascular disease treated with statins has been reported previously (Heart Protection Collaborative Study, Lancet 2004; 363:757). It is doubtful whether patients with a recent hemorrhagic stroke should be treated with statins at all, let alone a maximum dose of atorvastatin.

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Coenzyme Q10, a fat-soluble antioxidant also known as ubidecarenone, ubiquinone and CoQ10, is marketed as a dietary supplement in the US, both as a single ingredient and in various combination products.

The FDA recently approved the use of atorvastatin (Lipitor) to reduce the risk of heart attack and stroke in patients without heart disease who have type 2 diabetes plus other risk factors, with or without hypercholesterolemia. The agency also approved the drug's use to reduce the risk of stroke in high-risk nondiabetic patients without heart disease, whether or not they have hypercholesterolemia. Similar indications were previously approved for simvastatin (Zocor).

A highly concentrated omega-3 polyunsaturated fatty acid (PUFA) preparation (Omacor - Reliant) has been approved by the FDA as an adjunct to diet for treatment of very high plasma triglyceride concentrations (>=500 mg/dL). Omacor is a combination of the ethyl esters of icosapentaenoic (EPA) and docosahexaenoic (DHA) acids. It is the first drug derived from omega-3 PUFAs to be sold by prescription.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

Drugs that lower low-density lipoprotein cholesterol (LDL-C) concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions. In controlled trials in patients with coronary disease, some of these drugs have reduced mortality by 20% to 30%.

New guidelines from The National Cholesterol Education Program recommend, as a therapeutic option, lowering treatment goals for LDL cholesterol (LDL-C) from <100 mg/dL to <70 mg/dL for patients at very high risk for coronary heart disease and from 130 mg/dL to <100 mg/dL for those at moderately high risk. A likely consequence of these recommendations is increased use of statins and use of higher doses with a concomitant increase in adverse effects.

Vytorin, a fixed-dose combination of the cholesterol absorption inhibitor ezetimibe (Zetia - Merck/Schering Plough) and the HMG-CoA reductase inhibitor ("statin") simvastatin (Zocor - Merck), has been approved by the FDA for treatment of hypercholesterolemia. It is available as tablets containing 10 mg of ezetimibe combined with 10, 20, 40 or 80 mg of simvastatin.

Caduet (Pfizer), a combination of the calcium-channel blocker amlodipine (Norvasc - Pfizer) and the HMG-CoA reductase inhibitor (statin) atorvastatin (Lipitor - Pfizer), is now available in the US. It was approved by the FDA for use in patients with indications for treatment with both amlodipine, which is used to treat hypertension and/or angina pectoris, and atorvastatin, which is used to treat dyslipidemia. The combination is bioequivalent to the 2 components taken separately.

The recent "PROVE IT" trial in patients with coronary heart disease showed clinical benefits associated with reducing LDL cholesterol concentrations lower than the 100 mg/dL (2.59 mmol/L) or less that had been considered optimal.

Management of intermittent claudication, the most common symptom of peripheral arterial disease (PAD), involves both risk factor modification and symptomatic treatment (WR Hiatt, N Engl J Med 2001; 344:1608; RM Schainfeld, J Am Board Fam Pract 2001; 14:443).

Rosuvastatin (Crestor - AstraZeneca), an HMG-CoA reductase inhibitor (or "statin"), was recently approved by the FDA for lowering serum cholesterol and triglyceride concentrations and raising HDL cholesterol levels. Rosuvastatin, like other statins, inhibits the enzyme that catalyzes the rate-limiting step in cholesterol synthesis, but it is claimed to be more potent than the others. All of these drugs must be taken indefinitely; if they are discontinued, lipid levels return to baseline.

Drugs that lower low-density lipoprotein (LDL) cholesterol concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions, and also improve vasodilatation. In controlled trials in patients with coronary disease, they have reduced mortality by 30% to 40%. Lipid-regulating drugs must be taken indefinitely; when they are stopped, plasma lipid levels return to pretreatment levels in 2-3 weeks.

The FDA recently approved three new drugs for treatment of hyperlipidemia. Ezetimibe (ez et' i mibe; Zetia) is the first in a new class of drugs that inhibit intestinal absorption of cholesterol. Extended-release lovastatin (Altocor) is a new formulation of lovastatin (Mevacor, and others). Extended-release niacin plus (immediate-release) lovastatin (Advicor) is the first fixed-dose combination of lipid-lowering drugs.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

New recommendations for drug treatment of hypercholesterolemia, if widely followed, will lead to a marked increase in the number of people taking lipid-regulating drugs.

Many drugs are now marketed for prevention and treatment of postmenopausal osteoporosis. All regimens should include an adequate intake of calcium and vitamin D.

Amprenavir is the fifth protease inhibitor to become available for treatment of HIV infection. It was approved by the FDA for use with other drugs in the treatment of HIV-infected adults and children at least four years old.

Drugs that lower-density-lipoprotein (LDL) cholesterol concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions, improve coronary vasodilatation, and decrease mortality from coronary heart disease. All of these drugs must be continued indefinitely; when they are stopped, plasma cholesterol concentrations generally return to pretreatment levels. Elevated serum triglyceride concentrations appear to be an independent risk factor for cardiovascular disease in both women and men, but direct evidence of clinical benefit from triglyceride reduction is lacking.

Micronized fenofibrate (Tricor - Abbott), a fibric acid derivative structurally similar to clofibrate (Atromid-S, and others) and gemfibrozil (Lopid, and others), has been approved by the FDA for treatment of hypertriglyceridemia. Increased serum triglyceride concentrations have been associated with an increased risk of coronary heart disease (J Jeppesen et al, Circulation, 97:1029, 1998).

Cerivastatin (Baycol - Bayer), a new HMG-CoA reductase inhibitor (or "statin"), has been approved by the FDA for treatment of hypercholesterolemia. Cerivastatin is the sodium salt of a synthetic fluorophenyl pyridinyl-substituted heptanoic acid.

Drugs that lower elevated plasma cholesterol concentrations can prevent formation, slow progression and cause regression of atherosclerotic lesions, and may also improve coronary vasodilatation (JW Jukema et al, circulation, 91:2528, 1995: CB Treasure er al, N Engl J Med, 332:481, 1995; TJ Anderson et al, N Engl J Med, 332:488, 1995). All these drugs must be continued indefinitely; when htey are stopped, plasma cholesterol concentrations generally return to pretreatment levels.