Primecuts – This Week In The Journals

November 22, 2010

By Megha Shah, MD

Faculty Peer Reviewed

Things we love about Thanksgiving- turkeys, stuffing, mashed potatoes, pumpkin pie, and …Primecuts. Primecuts? Yes! What better way to be the life of your Thanksgiving party (those of you who are lucky and not working) than to share the latest in medical news with your loved ones? So sit back, grab a biscuit, and enjoy!

First off, a new drug to add to the arsenal of lipid-modifying agents? The New England Journal of Medicine this week reports the results of the Defining the Efficacy and Tolerability of CETP Inhibition with Anacetrapib (DEFINE) trial. Anacetrapib, marketed by Merck who also funded the trial, is a cholesteryl ester transfer protein inhibitor that raises high-density lipoprotein (HDL) cholesterol and reduces low-density lipoprotein (LDL) cholesterol. In this randomized, double-blind study, a group of 1623 patients with coronary heart disease already on a statin with acceptable LDL levels (defined as 50-100mg/dL) were randomized to receive either anacetrapib or placebo. The results showed that in 24 weeks, patients taking anacetrapib had a 39.8% reduction in their LDL beyond that seen in patients taking placebo (p<0.001). In addition, patients taking anacetrapib had a 138.1% increase in HDL beyond that seen with placebo (p<0.001). At 76 weeks, cardiovascular events occurred in 16 patients treated with anacetrapib versus 21 patients receiving placebo (p= 0.40). Though the authors of the study concluded that the drug significantly affects plasma lipid levels with an acceptable side-effect profile, whether the drug will significantly prevent cardiovascular events such as myocardial infarction remains to be seen. According to a statement by Merck in the New York Times, a larger study with researchers at Oxford University is currently underway with preliminary results expected in 2015. [1,2]

The Journal of the American Medical Association this week published a multi-center study on a new combination therapy for the treatment of hepatocellular carcinoma (HCC). In this study, 96 patients with advanced HCC, Eastern Cooperative Oncology Group (ECOG) performance status of zero (asymptomatic), and a Child-Pugh A status with no prior therapy were randomized to receive either doxorubicin with sorafenib or doxorubicin with placebo. Patients who received sorafenib with doxorubicin had a median overall survival of 13.7 months versus 6.5 for those received placebo (p<0.006) and progression-free survival of 6.0 and 2.7 months respectively (p<0.006) with similar safety profiles. Though this combination has not yet been approved for routine clinical use, it shows great promise. [3]

Early online publication of data presented at the American Heart Association’s Scientific Sessions 2010 in The Lancet shows that catheter based renal sympathetic denervation may be efficacious in the reduction of blood pressure in patients with treatment resistant hypertension. In this multicenter, randomized trial, 106 patients with refractory hypertension, defined as a systolic blood pressure of 160mm Hg or more while on three or more antihypertensive drugs, were randomized to either undergo renal denervation or continue with medical management. At six months, 84% of the patients who underwent renal denervation had a reduction in systolic blood pressure of 10mm Hg or more versus 35% of those who continued medical management (p<0.0001). While complications from the catheter based procedure were minimal and results positive, further large scale studies will be needed to better define the appropriate indications and usage. [4]

Be careful what you breathe! In a study published in the Journal of the American College of Cardiology, researchers in Germany assessed the association of urban particulate matter (PM) and carotid intima-media thickness (CIMT). Researchers used data from the Heinz Nixdorf Recall (HNR) study which looks at risk factors associated with subclinical atherosclerosis in approximately 5,000 participants. Of that total, 3,380 were identified as living in high traffic areas with PM levels measured by chemistry transport models. The results showed that participants living in high PM areas had a 4.3% increase in CIMT over those who did not. While the study authors concluded that air pollution may have a measurable effect on atherogenesis, further confirmatory studies will need to be done. This study though does point out air pollution as a cardiovascular risk factor that may be overlooked and that, down the line, may be used to identify high risk populations. [5]

Lastly, another reason not to use post-menopausal hormone replacement therapy. The New York Times  reports on findings from the European Prospective Investigation into Cancer and Nutrition. According to the data, which was presented at the American Association for Cancer Research earlier this month, women who use hormone replacement therapy are at an increased risk for ovarian cancer. The study, which included approximately 130,000 postmenopausal women over a period of nine years, showed that those on HRT had a 29% greater risk of ovarian cancer. Further, women with hysterectomies who used estrogen-only replacement had a 63% increased risk. Though official statistical analyses are not yet complete, this likely is a topic that will need to be discussed more thoroughly with our patients in the future. [6]

That’s it for this weeks’ Primecuts- here’s wishing you and your loved ones a happy Thanksgiving and an even happier Black Friday!

Dr.  Shah is a 2nd-year resident at NYU Langone Medical Center

Judith Brenner, MD, is an associate editor, Clinical Correlations

Image Courtesy of Wikimedia Commons

References:

1.  Cannon CP, Shah S, Dansky HM et al. Safety of Anacetrapib in Patient with or at High Risk for Coronary Heart Disease. NEJM. Published online November 17, 2010.

2.  Singer, Natasha. Merck Drug for Cutting Cholesterol is Promising. New York Times. November 17, 2010.  http://www.nytimes.com/2010/11/18/health/research/18merck.html

3.  Ghassan KA, Johnson P, Knox JJ et al. Doxorubicin Plus Sorafenib vs. Doxorubicin Alone in Patients with Advanced Hepatocellular Carcinoma. JAMA. 304 (19): 2154-2160. November 2010.

4.  Esler, Murray et al. Renal Sympathetic Denervation in Patients with Treatment-Resistant Hypertension (the Symplicity HTN-2 Trial): a Randomized Controlled Trial. The Lancet. Early online publication. November 17, 2010.  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62039-9/fulltext

5.  Bauer M, Moebus S, Mohlenkamp S et al. Urban Particulate Matter Air Pollution Is Associated With Subclinical Atherosclerosis. J Am. Coll. Cardiol. Vol 56: 1803-1808. 2010.  http://content.onlinejacc.org/cgi/content/abstract/56/22/1803

6.  Rabin, RC. Study Ties Ovarian Cancer and Hormone Therapy. New York Times. November 12, 2010.

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