Primecuts-This Week in the Journals

December 17, 2012

By Shyam Amin, MD

Faculty Peer Reviewed

 Welcome back to Clinical Correlations! These last couple months have been largely dominated by Hurricane Sandy and its aftermath. Just as New York City has landed back on its feet, we here at the NYU Department of Medicine and Clinical Correlations are determined to continue our mission to practice medicine with the best evidence available.

While our beloved Manhattan VA remains closed, our colleagues at the Minneapolis VA released an observational study in the Archives of Internal Medicine that looked at the optimal treatment duration for UTI in men. The study used the VA Outpatient Events file, which contains outpatient notes for nearly 5 million patients. Using this database, the authors identified 39,149 urinary tract infection (UTI) cases based on ICD9 codes and prescriptions written. The study compared shorter duration treatment (<=7 days) with longer duration treatment (>7 days) and the effect on UTI recurrence and C difficile infection. The results showed that longer-duration treatment showed no reduction in recurrence rate but did have significantly higher risk of C difficile infection. Although this study was not a randomized trial, it certainly makes a strong case for shorter-duration treatment for UTI in male outpatients.

An interesting randomized trial was released last week in Annals of Internal Medicine assessing the efficacy of a Clinical Decision-Support System (CDSS) in an HIV clinic. The CDSS was a computer alert given to the provider for three adverse events: virologic failure, suboptimal follow-up, and laboratory toxicity. The control group received static alerts on the patient-specific electronic medical record (EMR) page, whereas the intervention received interactive alerts viewed on the provider’s EMR home-page as well as in biweekly emails. The interactive alerts were optimized to prevent “alert fatigue” and to allow quick interventions, such as rescheduling a clinic visit with only a couple mouse clicks. The results of the study showed significantly increased CD4 cell counts (0.0053 vs 0.0032 x 109 cells/L per month; P = 0.040) and improved rate of suboptimal follow-up (20.6 vs. 30.1 events per 100 patient-years; P = 0.022). In the bigger picture, the study highlights the potential of using smart, streamlined alert systems in our EMR to improve patient care.

In the exciting realm of lipidology, a phase 2 clinical trial was reported in Lancet last week providing further evidence in support of PCSK9 inhibition in reducing LDL concentrations. PCSK9 is an intracellular protein that aids in the degradation of LDL receptors; inhibition of PCSK9 conversely increases LDL receptor concentration and thus allows greater rate of LDL uptake by hepatocytes. PCSK9 inhibition has recently become the hot new pharmacologic target in aims to lower LDL concentration. This study reports the efficacy and tolerability of AMG 145, a human monocloncal antibody against PCSK9, in patients with hypercholesterolemia on a statin. Subjects were randomly assigned to receive varying doses of AMG 145 given by subcutaneous injections at either 2 week or 4 week intervals. The results were impressive, with generally dose dependent reduction in LDL concentrations by 41.8% to 66.1% (p < 0.0001 for each dose vs placebo). The medication was well-tolerated, with similar rates of adverse events related to study drug between the intervention group and placebo (8% vs 7%) and no serious adverse events reported. A similar phase 2 clinical trial of AMG 145 was also published this week in Lancet for patients with hypercholesterolemia not currently on statins and reported similarly impressive results. These two studies of AMG 145, along with another recently studied PCSK9 antibody SAR236553/REGN727, show great promise for PCSK9 inhibition and represent what could soon become a new model for lipid management.

Finally, in Circulation last week is an article that continues to assess whether rhythm verse rate control should be preferred in patients with atrial fibrillation. The article reported a population-based observational study comparing rates of stroke or transient ischemic attacks in patients with atrial fibrillation being treated with either rhythm control or rate control. The results showed reduced stroke/TIA rate in the rhythm control group (1.74 versus 2.49, per 100 person-years, P < 0.001); the results remained significant after multivariable analysis (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74, 0.87). We all know the landmark AFFIRM trial that was a randomized control trial comparing rate and rhythm control. The authors of this article argue that the AFFIRM trial and other similar randomized controlled trials lacked adequate sample size to accurately report stroke rate, and therefore in their opinion, this population-based study is a more appropriate analysis. In my opinion, this study will not make me change the way I treat my patients with atrial fibrillation as the slightly reduced stroke risk with rhythm control is not quite enough to overcome the increased risk of adverse events with antiarrhythmics, but the article certainly is good food for thought. 

Dr. Shyam Amin is a resident at NYU Langone Medical Center 

Faculty Peer Reviewed by Neil Shapiro, MD, Editor-In-Chief, Clinical Correlations 

A few other notable articles this week:

1. Effect of Legumes as Part of a Low Glycemic Index Diet on Glycemic Control and Cardiovascular Risk Factors in Type 2 Diabetes Mellitus-This Archives of Internal Medicine article shows that diets supplemented with lentils, chickpeas, and beans can significantly improve your patients’ glycemic control.

2. Myocardial Infarction and Sudden Cardiac Death in Olmsted County, Minnesota, Before and After Smoke-Free Workplace Laws-Another article in Archives of Internal Medicine gives evidence that second hand smoke can increase your risk of myocardial infarction and sudden cardiac death.

3. Upper Endoscopy for Gastroesophageal Re?ux Disease: Best Practice Advice from the Clinical Guidelines Committee of the American College of Physicians-In the Annals of Internal Medicine, the ACP released updated guidelines for endoscopy in the management of GERD.