PrimeCuts: This Week in the Journals

March 15, 2010

bellevuehospitalChristopher Tully MD

Faculty peer reviewed

Hello again Primecutters and welcome to another edition of your favorite weekly blog. Our fearless editor has allowed me a repeat performance of last week and I am honored to provide the followers of this column with another scintillating tale of the week’s medical knowledge.Dyslipidemia is a common clinical problem and its control is a mainstay of inpatient and outpatient internal medicine. While statins are miraculous in their ability to treat and control abnormal lipid levels, many patients require additional medical treatment to reach pre-determined goals. In an effort to widen the options for these secondary agents, researchers publishing in the NEJM studied the role of the thyroid hormone analog, eprotirome, in the treatment of dyslipidemia (1). Thyroid hormones are known to reduce LDL through a mechanism of increased hepatic clearance due to increased expression of the hepatic LDL-receptor gene. This randomized, placebo-controlled, double blind, double-dummy trial enrolled 189 patients on stable statin therapy to receive either eprotirome or placebo for 12 weeks. The study found that compared to placebo, increasing doses of eprotirome (25, 50 or 100 micrograms) produced statistically significant decreases in LDL, apolipoprotein B, lipoprotein (a), and triglycerides at 12 weeks. Study participants achieved these decreases without significant adverse effects associated with excess thyroid hormone including tachycardia, weight loss, atrial dysrhythmias or accelerated bone turnover. While this paper clearly provides evidence for eprotirome as an adjunct agent, there are still questions regarding its overall benefit and worth. Firstly, there is the undesirable decrease in HDL and apolipoprotein A-I, conferring an increased cardiovascular risk on the studied population. Secondly, although the primary outcome called for analysis at 12 weeks, based on the provided graphs and tables many of the reductions in LDL, apolipoprotein B and lipoprotein (a) achieved at 12 weeks appear to normalize back to pretreatment levels at 16 weeks, raising concern for treatment tolerance. Finally, excess thyroid hormone is not a benign treatment and although the side effect profile was minimal to none in this trial, concern must be raised for more increased adverse effects in a larger trial population. So while eprotirome clearly has academic benefit in the treatment of dyslipidemia, clinically there are still many unanswered questions.

In the world of anticoagulation, there are truly only two outpatient options, the potentially harmful and difficult to control oral vitamin K antagonists or inconvenient and expensive injectable Xa inhibitors. There is, however, a growing body of evidence surrounding the use of orally active factor Xa inhibitors (such as apixaban or rivaroxaban). Building on the work by the RECORD investigators with rivaroxaban, the ADVANCE investigators, publishing in the Lancet, compared the use of apixaban to enoxaparin in a randomized, double-blind, phase 3 trial of patients undergoing elective unilateral or bilateral total knee replacement (2). The primary outcome was a composite of adjudicated asymptomatic or symptomatic deep venous thrombosis, non-fatal pulmonary embolism and all-cause death for a period of 12 days or within 2 days of last drug delivery. The primary outcome occurred in 147 (15%) of patient’s receiving apixaban versus 243 (24%) receiving enoxaparin, for a relative risk reduction of 0.62 and absolute risk reduction of 9.3%. The adverse effect of bleeding was similar between the two populations. As the evidence supporting the use of oral Xa inhibitors as prophylaxis for venous thromboembolism in surgical procedures grows, it is reasonable to assume that we will see investigations of the use of these agents in common internal medicine morbidities such as atrial fibrillation and deep venous thrombosis, perhaps providing physicians and patients with another safe and convenient, albeit expensive, anti-coagulation treatment option.

In this era of economic hardship and budget shortfalls, many state governments are struggling to find ways to pay for services that constituents expect while not further punishing already financially strapped citizens. In New York, a state not afraid to enact legislation to curb harmful societal habits (high cigarette taxes and ban on smoking in bars, and the trans-fat ban in New York City), the current governor is proposing a ban on sugary drinks as a way to increase the state’s coffers while improving the population’s health. While this issue is far beyond a strictly health-driven policy decision, researchers in the Coronary Artery Risk Development in Young Adults (CARDIA) study publishing in the Archives of Internal Medicine analyzed the effect of price on the intake of soda and pizza (3) and found results that many support the governor’s plan. Although extrapolating this data is difficult given the limits of the food studied, their research indicated that price increases in soda and pizza were associated with significant declines in overall daily energy intake, lower weight and decreased insulin resistance scores among the studied participants. Although not clear-cut, these studies show that the local, state and national policies directed toward altering the price of less healthy foods may serve as an option in steering individuals toward more healthy diet choices.

Finally, although the shock of the earthquake in Haiti is fading, those interested in learning more about the healthcare story in the impoverished country should read Mountains Beyond Mountains by Tracy Kidder, which tells the story of Paul Farmer and his Boston-based non-profit Partners in Health (4). It is a truly inspiring story regarding the work of a small group of devoted healthcare providers and the type of work that can be accomplished. As Tracy Kidder published in the NEJM, the presence of Partners in Health in Haiti at the time of earthquake surely saved thousands of lives during the initial chaos of the event (5).

Thanks again for taking the time to follow with Primecuts. I do not think I will be back for a third week, so until the next time, keep reading.

Faculty peer reviewed by Barbara Porter MD MPH,  Clinical Assistant Professor of Medicine, NYU Medical Center

1) Ladenson, Paul W. et al. Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia. NEJM 2010;362(10):906-916.

2) Lassen, Michael Rud et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomized double-blind trial. Lancet 2010;375 (807-815).

3) Duffey, Kiyah et al. Food Price and Diet and Health Outcomes: 20 Years of the CARDIA Study. Arch Intern Med 2010;170(5):420-426.

4) Kidder, Tracy. Mountains Beyond Mountains: Healing the World: The Quest of Dr. Paul Farmer, A Man who would Cure the World. Random House; September 9, 2003

5) Kidder, Tracy. Recovering from Disaster – Partners in Health and the Haitian Earthquake. NEJM 2010:362(9):769-772.