Cholesterol management guidelines from the American College of Cardiology/American Heart Association Task Force were last published in 2019.

View the Comparison Table: Some Lipid-Lowering Drugs

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.

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain and altered bowel habits, often accompanied by bloating.IBS is classified according to the predominant bowel symptom as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), or unclassified (IBS-U). Alterations in the microbiome, stress responses, sensory and motor function of the gut, and host genetic factors may be contributing factors. Since the exact cause of IBS is unknown, the goal of treatment is symptom control.

View the Table: Safety of Drugs for IBS in Pregnancy and Lactation

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

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.

Irritable bowel syndrome (IBS) is a common disorder characterized by chronic, intermittent abdominal pain or discomfort and altered bowel habits. It is subtyped according to the predominant bowel symptom as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), or unclassified (IBS-U). Since the exact cause of IBS is unknown, the goal of treatment is symptom control.

The treatment of atrial fibrillation includes anticoagulation, rate control, and rhythm control. New US guidelines for the management of atrial fibrillation have recently 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.

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 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.

A reader expressed disappointment that our recent listing of “Some Warfarin Drug Interactions”1 did not include acetaminophen. Perhaps it should have. Acetaminophen can increase the anticoagulant effect of warfarin, particularly with continued use, but it does so inconsistently. The mechanism of this interaction has not been established, but may be related to an acetaminophen metabolite inhibiting vitamin K-epoxide reductase, the target for warfarin’s anticoagulant effect.2

Patient susceptibility varies, possibly on a genetic basis; occasional use of acetaminophen generally has little or no effect on the international normalized ratio (INR) in patients on chronic warfarin therapy, but in some, even a few grams of the drug may cause a dramatic increase in INR. One study in healthy subjects found no effect of acetaminophen 4 g per day for 2 weeks, while another study in patients with the same acetaminophen dose for the same period of time found a moderate increase in INR.3,4 It might be prudent to monitor INR in patients on chronic warfarin therapy more closely than usual when they take more than 2 g per day of acetaminophen for more than a few days.

1. Pharmacogenetic-based dosing of warfarin. Med Lett Drugs Ther 2008; 50:39.
2. HH Thijssen et al. Paracetamol (acetaminophen) warfarin interaction: NAPQI, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle. Thromb Haemost 2004; 92:797.
3. D Kwan et al. The effects of acetaminophen on pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 1999; 39:68.
4. I Mahe et al. Paracetamol: A haemorrhagic risk factor in patients on warfarin. Br J Clin Pharmacol 2005; 59:371.

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Warfarin sodium (Coumadin, and others) and other coumarin anticoagulants prevent thrombosis, but patient response is highly variable and overanticoagulation can lead to hemorrhage. Genotyping patients for single nucleotide polymorphisms (SNPs) that affect coumarin metabolism and sensitivity may help clinicians estimate the therapeutic warfarin dose. The FDA has added a note to warfarin labeling recommending lowrange doses for patients with such genetic variations. Commercial tests for these variants are now available and cost about $500 per test.

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.

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%.

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.

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.

Colesevelam hydrochloride (Welchol - Sankyo Pharma), a nonabsorbed hydrophilic polymer that binds bile acids, has been approved by the FDA for reduction of plasma LDL cholesterol in patients with primary hypercholesterolemia.

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).

Atorvastatin (Lipitor - Parke-Davis), an HMG-CoA reductase inhibitor (or 'statin'), was recently approved by the US Food and Drug Administration for treatment of primary hypercholesterolemia and mixed dyslipidemia. A single stereoisomer of a pyrrole derivative, the new drug is chemically different from other statins.

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.

Fluvastatin (Lescol - Sandoz), an HMG-CoA reductase inhibitor, was recently marketed in the USA for treatment of hypercholesterolemia. A synthetic mevalonolactone derivative, it is chemically distinct from previously available drugs in this class.

Lowering elevated serum cholesterol concentrations can slow progression and sometimes cause regression of atherosclerotic lesions. Most authorities advise patients with high cholesterol concentrations to eat less fat and less cholesterol and, when appropriate, to lose weight. If these measures do not lower serum lipids sufficiently, drugs are frequently added to the regimen. When drugs are discontinued, serum cholesterol concentrations generally return to pretreatment levels.

Pravastatin - Bristol-Myers Squibb) and simvastatin (Zocor -Merck), two new inhibitors of cholesterol synthesis similar to lovastatin (Mevacor - Merck), have now been marketed in the USA for treatment of hypercholesterolemia. Lovastatin (Medical Letter, 29:99, 1987) is the most frequently prescribed of all cholesterol-lowering drugs in the USA. Pravastatin and simvastatin were previously reviewed in The Medical Letter when they became available in Canada (volume 33, page 18, 1991).

Pravastatin (Pravachol - Bristol-Myers Squibb) and simvastatin (Zocor - Merck), two new inhibitors of cholesterol synthesis similar to lovastatin (Mevacor - Merck), have been marketed in Canada and several European countries and may soon be available in the USA for treatment of high plasma cholesterol concentrations. Drugs already marketed here for this indication were recently reviewed in The Medical Letter (Volume 33, page 1, January 11, 1991).

Recent reports indicate that lowering elevated serum cholesterol concentrations not only decreases mortality from coronary artery disease, but may cause regression of atherosclerotic lesions (JP Kane et al, JAMA, 264:3007, Dec 19, 1990). Most authorities advise patients with high cholesterol concentrations to eat less saturated and total fat and lose weight. If these measures do not lower serum lipids, drugs are frequently added to the regimen. When drugs are discontinued, serum cholesterol concentrations generally return to pretreatment levels.

The recent surge of interest in lowering serum cholesterol concentrations has led to vigorous promotion of various hypocholesterolemic drugs in the USA. Since the risk of coronary heart disease is increased in patients with high serum cholesterol concentrations, most authorities advise such patients to eat less fat and try to lose weight (The Expert Panel, Arch Intern Med, 148:36, 1988). When these measures fail, cholesterol-lowering drugs are frequently recommended.