Primecuts: This Week In The Journals

June 1, 2010

By Mario Fusaro, MD

Faculty Peer Reviewed

We begin this week’s Memorial Day edition of Primecuts by taking a moment to recognize the service men and women of our country.  As people celebrated the holiday weekend with barbeques and beach trips, we should not lose sight of its main significance, to honor those charged with protecting our way of life.  While the veteran population ages, they look to us to protect their health as they once protected our freedoms.   As medical personnel, we can honor this debt by striving for excellence and providing the best possible care to those who have already provided for us.  In doing so, we can give back something truly tangible and exhibit our very own gesture of thanks. 

 Primecuts starts on a topic affecting many veterans, Chronic Obstructive Pulmonary Disease (COPD).  COPD is one of the leading causes of morbidity and mortality in the US today.  The mainstays of treatment include oxygen, bronchodilators and steroids.  A host of other treatments such as: lung-volume reduction surgery, antibiotics and now β-blockers are emerging.  This week, The Archives of Internal Medicine challenges the widely held belief that beta blockers are contraindicated in COPD.  They  published an observational cohort study[1] looking at the impact of of cardioselective and non-cardioselective β-blockers on all-cause mortality and COPD exacerbations in patients with and without cardiac related comorbidities.  The study followed 2,230 COPD patients 45 years of age and older for an average of 7.2 years.  After controlling for severity of illness, the authors showed a reduction in all cause mortality in the β-blocker treated cohort HR 0.68 (95% CI, 0.56-0.83) as well as a reduction in COPD exacerbations HR 0.71 (95% CI, 0.60-0.83) in the same group.  Sub group analysis revealed similar outcomes in patients with no overt cardiovascular disease and even more benefit in patients taking only cardioselective β-blockers.  As cardiovascular disease is a common cause of mortality in COPD patients, it would stand to reason that β-blockers might reduce this risk.  The surprising reduction in the primary endpoint in patients seemingly free of cardiac disease begs the question, is there another mechanism by which β-blockers improve the disease or is there actually a hidden cardiac process at work?

 Speaking of  COPD, JAMA this week revisits the role of antibiotics in the treatment of COPD exacerbations.  Although there are several possible etiologies for COPD exacerbations, pulmonary infection is felt to be the most common[2].  This study was a retrospective analysis[3] of 84,621 patients over 40 years of age admitted with an acute COPD exacerbation.  The authors reviewed the effect of antibiotic treatment on the primary endpoints: rate of in hospital mortality, readmission within 30 days or rate of mechanical ventilation 2 days after admission. In patients taking antibiotics, in-hospital mortality was reduced (1.59% to 1.04 %), as was mechanical ventilation rates (1.80% vs. 1.07%) and readmission rates were also reduced (8.79% vs. 7.91%). 

Not surprisingly, rates of C. difficile infection were increased in the antibiotic group.  In the past, antibiotics were only considered efficacious in those with changes in sputum production and/or quality of sputum.  These authors suggest a role for antibiotics in all exacerbations.  It remains to be seen what this liberal use of antibiotics might have on patterns of antibiotic resistance in the future.

 Switching organ systems, we turn to discussion of two drugs which have received quite a bit of press lately, the proton pump inhibitors (PPI) and histamine-2 receptor blockers (H2).   These two classes are some of the most widely prescribed drugs in America today.  Recently, they have come under fire due to possible associated increased rates of pneumonia, clopidogrel ineffectiveness and increased rates of C. difficile colitis.  The FDA has most recently warned that an increased risk of hip fractures can be added to these concerns..  This finding was demonstrated in the journal Gastroenterology.  In a case-control study[4] of 164,223 patients over 10 years, the authors compared patients with and without hip/femur fracture and their use of  PPI or H2RA.  The authors found that there was an increased risk of fracture in the patients currently using PPI for >2 years with at least one comorbid condition (i.e. alcoholism, glucocorticoid use and renal disease) OR 1.25 (95% CI, 1.16-1.35) but no increased risk in those without comorbidities.  These findings were also noted in the H2 drugs but to a lesser extent.  There was a dose-dependent relationship observed with higher daily doses of PPI causing more disease.  After cessation of these meds, the risk of fracture decreased proportionally over time.  Although these findings shed more light on the risks of widespread usage of acid suppressing agents, more prospective studies are needed to determine the risk/benefit ratio in certain patient populations.  Regardless we all need to think twice maybe trhee times before we commit a patient to longterm acid suppression.

 For the final section of Primecuts, we embark on the topic of carotid endarterectomy (CEA) vs. carotid stenting for the treatment of carotid-artery stenosis (CAS).  A recent publication in the New England Journal of Medicine examines the two therapies.  This study was a randomized controlled trial[5] of 2502 patients with symptomatic and asymptomatic CAS defined as CAS >50% by angiography and >70% by ultrasound or CT.  The primary endpoints were stroke, myocardial infarction (MI), death within the periprocedural time (within 30 days of procedure) or stroke within 4 years thereafter.  The study revealed a non-significant difference in mortality between the two methods at any time.  There was an increased risk of stroke with stenting versus CEA during the peri-procedural period (HR 1.79 [1.14-2.82] p=0.01) and within 4 years post procedure (HR 1.40 [1.04-1.89] p=0.03).  However, during the periprocedural period, there was an increased risk of MI with CEA vs. stenting of 2.3% vs. 1.1% (p=0.03), respectively.  Ultimately, the authors concluded that there was no clear superior method based on patient outcomes.  This study highlights the challenges faced in deciding which therapy to choose for which patient.  Similarities in outcome and differences in predominating complications incurred leave providers to essentially ‘pick-their-poison.’  With no clear superior method, providers will likely choose a therapy based on their own biases and experience.

Dr. Fusaro is an incoming first year resident at NYU Langone Medical Center

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

Works cited 

1.  Rutten F, Zuithoff PA, Hak E, Grobbee DE, Hoes AW. β-Blockers May Reduce Mortality and Risk of Exacerbations in Patients With Chronic Obstructive Pulmonary Disease. Arch Intern Med. 2010;170(10):880-887.

2.  Rosell A, Monsó E, Soler N, Torres F, Angrill J, Riise G, Zalacaín R, Morera J, Torres A. Microbiologic Determinants of Exacerbation in Chronic Obstructive Pulmonary Disease. Arch Intern Med. 2005;165:891-897.

3.  Rothberg MB, Pekow PS, Lahti M, Brody O, Skiest DJ, LindenauerPK. Antibiotic Therapy and Treatment Failure in Patients Hospitalized for Acute Exacerbations of Chronic Obstructive Pulmonary Disease. JAMA. 2010;303(20):2035-2042

4.  Corley DA, Kubo A, Zhao W, Quesnberry C. Proton Pump Inhibtors and Histamine-2 Receptor Antagonists Are Associated With Hip Fractures Among At-Risk Patients. Forthcoming 2010.

5.  Brott TG, Hobson RW, Howard G, Roubin GS, Clark WM, Brooks W, Mackey A, Hill MD, Leimgruber PP, Sheffet AJ, Howard VJ, Moore WS, Voeks JH, Hopkins LN, Cutlip DE, Cohen DJ, Popma JJ, Ferguson RD, Cohen SN, Blackshear JL, Silver FL, Mohr JP, Lal BK, Meschia JF, for the CREST Investigators. Forthcoming 2010.