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19 January 2010 Annals of Internal Medicine Tip Sheet

Annals of Internal Medicine is published by the American College of Physicians on the first and third Tuesday of every month. These highlights are not intended to substitute for articles as sources of information. For a copy of an article, call 1-800-523-1546, ext. 2656, or 215-351-2656, or visit www.annals.org. Past highlights are accessible as well.

1. Prescribed Opioids Associated with Significant Risk for Overdose

Prescriptions of some opioids, such as oxycodone, have increased significantly over the past decade. As long-term opioid therapy for chronic noncancer pain becomes more common, the deaths associated with opioids increase. Opioid overdose is among the most common causes of death nationwide. Researchers sought to determine the rate of opioid overdose in relation to an average prescribed daily opioid dose among patients receiving medically-prescribed, long-term opioid therapy. Researchers observed 9,940 adults receiving at least three opioid prescriptions for chronic noncancer pain within 90 days. Fifty-one of the 9,940 adults receiving long-term opioid therapy had one or more overdose events during follow-up. Six of those events were fatal. Most of the observed overdoses occurred in patients receiving lower opioid doses although risks for overdoses increased for patients receiving higher doses. Due to uncertainties regarding effectiveness and the risk for overdose, long-term opioid therapy should be prescribed carefully for noncancer pain. Researchers recommend that physicians closely monitor opioid patients, dose judiciously, and continually reevaluate the benefit of the drugs. A. Thomas McLellan, PhD., author of an editorial on the study and Deputy Director of the White House Office of National Drug Control Policy states, “The threat to patient safety is too great to allow current pain management and opioid prescribing practices to remain as they are.”

2. Leptin Therapy Could Hold Key to Long-term Weight Loss

Hormone Helps to Regulate Energy Homeostasis, Neuroendocrine Function, and Metabolism

Leptin is a hormone that plays a central role in fat metabolism. Patients with genetic leptin deficiency are obese, and treatment with leptin leads to dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese people who produce leptin normally are resistant to the weight-loss effects of the hormone. Leptin deficiency is a clinical syndrome associated with distinct conditions such as recent weight loss, diet- or exercise-induced hypothalamic amenorrhea, and lipoatrophy. Recombinant human leptin is an emerging potential therapy for these leptin-deficient conditions because in replacement doses, it normalizes energy homeostasis, neuroendocrine function, and metabolism. Replacement of leptin in physiologic doses may help people who have recently lost weight because relative leptin deficiency may drive them to eat more, expend less energy, and regain weight. Leptin also restores ovulatory menstruation in women with hypothalalmic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy.

3. Atrial Fibrillation Risk Lower with Some Classes of Antihypertensives

Atrial fibrillation, or irregular heartbeat, is a major risk factor for thromboembolic events, particularly stroke. This risk is especially high in patients with high blood pressure. Antihypertensive drugs are known to reduce the risk for atrial fibrillation by lowering blood pressure. However, some classes of antihypertensives may have greater risk reduction through other mechanisms. Researchers studied 4,661 patients with atrial fibrillation against 18,642 matched control patients from a population of 682,993 patients treated for hypertension in the United Kingdom. They compared the risk for atrial fibrillation among hypertensive patients taking angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or beta-blockers to the reference group taking calcium channel blockers. The researchers found that patients on long-term ACE-inhibitor, ARB, or beta blocker therapy had a reduced risk for atrial fibrillation compared to patients on calcium channel blockers. Patients and physicians should consider these differences when choosing an antihypertensive therapy.

4. Higher Statin Doses Not Always Best at Preventing Coronary Artery Disease

Statins have proven highly effective at lowering cholesterol. Typically, a treat-to-target approach, which means treating to a target cholesterol level, is taken with statin therapy. However, some experts believe that a tailored approach that uses different dosages based on pateints’ risk for cardiovascular disease may be a better strategy for reducing the risk of coronary artery disease. Researchers developed a computer simulation to compare two treatment approaches at the population level-- giving fixed doses of statins on the basis of a person’s five-year coronary artery disease risk (tailored treatment), or increasing statin doses to achieve particular lipid level targets (treat-to-target). Compared with the intensive treat-to-target approach, the tailored fixed-dose strategy saved more quality-adjusted life-years and treated fewer persons with high-dose statin therapy. Researchers conclude that tying statin treatment individual risk for heart disease and potential benefits may be better than approaches that focus primarily on achieving certain lipid level targets.