Primecuts – This Week In The Journals

January 10, 2011

By Michelle Scott, MD

Faculty Peer Reviewed

 It’s a new year and while our resolutions are meant to give us a fresh start- curb our spending, shed a few pounds, call our family more often- the reality is you don’t feel any different. You look the same, weigh the same (okay, maybe you’re a few pounds heavier after the holidays), have the same daily routine, but things are changing and fast. Where? On the hill. This past Wednesday, John Boehner was officially elected the new speaker of the house. Although first up on the Republican-lead congressional agenda is to dismantle the recent health care legislation, one of the earliest changes was actually initiated by the Obama administration. It was the deletion of advanced care planning as a covered service in the annual wellness visit for Medicare recipients [1].  This service, while officially dropped from health care reform following cries about “death panels,” had been picked up again in a new Medicare regulation set forth by Dr. Donald Berwick, head of Medicare/Medicaid services, in November.  The media speculates that the decision to delete this reference from the regulation was a move by democrats to focus their defenses on the health care bill.  However, many doctors and health care providers, regardless of their political inclinations, are likely to lament the loss of advanced care planning; one of the most important interactions we can have with our patients.

 In a recent featured article in Critical Care Medicine, Sanders et al. highlight the importance of discussing end of life issues and goals of care in their critique of partial do-not-resuscitate orders [2].  While partial orders are only thought to account for a small fraction of all DNR orders (<10%), they are increasingly popular.  The authors acknowledge that the purpose of a partial DNR is to allow patients to choose resuscitative efforts that match their concept of a tolerable death.  However, they propose that partial DNR orders may result in non-beneficial or even harmful therapy.  The therapeutic benefit of partial DNRs depends on the combination of therapies chosen, which requires the patient to comprehend the various treatments and their interactions.  As the authors phrase it “Choosing to include or exclude one element of a larger combination of treatments may inadvertently prevent what otherwise would be a successful resuscitation.” As an example they site a study which found that 104 of 445 patients (23%) who received full resuscitation survived until discharge, compared to 0 of 37 patients receiving partial resuscitation.  The authors recommend that providers discourage the use of partial DNR orders and rather engage in more accurate and comprehensive advanced care planning of which the DNR decision is only a part.  As an intern, I think “this is great in theory, if only there were more hours in a day.” However, it is incumbent upon us to keep these discussions on our radar, as they are one of the most beneficial interventions for our patients, ultimately shaping all their future medical care.

 Other critical care issues were also featured in the journals this week.  The Lancet published an article by Clifton et al, which attempted to assess the neuroprotective benefits of hypothermia in severe brain injury [3].  Extrapolating from data that showed mortality benefits from hypothermia protocols in cardiac arrest, the authors designed a randomized control trial that compared outcomes in patients with severe brain injury who were managed with early cooling (33°C for 48h) to those kept normothermic.  The primary outcome was general recovery and functional status 6 months after the event as determined by the Glasgow outcome scale score. Secondary outcomes included in-hospital complications and the number of interventions required in patient management.  There was no significant difference in outcomes between the groups. Thirty-one of 52 patients in the hypothermia group suffered severe disability or were in a vegetative state compared to 25 of 56 patients in the normothermia group (RR 1.08, 95% CI 0.76-1.53; p=0.67).  There was a 23% mortality rate amongst the hypothermia group compared to 14% in the normothermia group (RR 1.30, 95% CI 0.58-2.52; p=0.52).  However, patients in the hypothermia group received significantly more interventions in the first 96 hours than patients in the control group. This study thus showed no neuroprotective effects from hypothermia and was terminated early for futility.  Nevertheless, it is a good reminder that negative studies are also important in shaping evidenced-based patient management.

 Staying up to date with the evidence is the purpose of Primecuts and for us newly minted physicians we are taught that first and foremost we should follow the evidence whenever possible.  So how do we justify our actions when they seem contrary to the evidence?  Well, the New York Times is asking just that about implantable cardioverter defibrillators (ICD’s) [4].  In a retrospective cohort study published in JAMA, Al-Khatib et al found that 22.5% of ICD’s in the US were placed despite patients not meeting the criteria for device implantation [5].  The 2008 Guidelines for Device-Based Therapy indicate that ICDs should be used in patients with New York Heart Association (NYHA) class II/III heart failure with left ventricular ejection fractions (LVEF) <35% due to a prior myocardial infarction (MI) or nonischemic dilated cardiomyopathy (NIDCM) or NYHA class I heart failure with LVEF <30% from prior MI [6]. All patients should be at least 40 days post-MI and have received optimal medical therapy (implicitly excluding a new diagnosis of heart failure). ICD therapy is not indicated in patients with survival <1 year or in patients with class IV heart failure who are not candidates for cardiac transplantation or cardiac resynchronization therapy defibrillator (CRT-D) as their 1 year survival is low. Analyzing 111,707 cases submitted to the National Cardiovascular Data Registry/ICD Registry, the authors found that of patients with non-evidenced based devices (NEBD) 37% were within 40 days of a MI, 3.2% within 3 months of CABG, 12% with class IV heart failure, and 62% with newly diagnosed heart failure. Alarmingly, in-hospital death was significantly higher in NEBD patients compared to patients who met criteria (0.57% vs. 0.18%; p<0.001).  In addition, they were at higher risk for post-procedure complications including hematoma and death (3.23% vs 2.41%; p<0.001).  Median hospital stay was also significantly longer (3 days vs 1 day; p<0.001).  However, NEBD patients were also significantly older with more comorbid diseases, including AF/flutter, CVA, chronic lung disease, diabetes and ESRD, than patients receiving evidenced-based devices.  Given that the NEBD group had more comorbid disease and included sicker class IV heart failure patients, the group repeated analysis excluding class IV HF patients.  The rates of post procedure complications and death remained significantly higher in NEBD patients.  The group also assessed device placement by physician specialty: electrophysiologist had the lowest implant rates at 21%, followed by non-electrophysiolgist cardiologist at 25%, thoracic surgeons at 36%, and other specialties at 25% (p<0.001 for all comparisons). This study raises concerns that patients are suffering complications from procedures that are being performed without clear indications or survival benefits. In interviewing the authors, the NY Times probed for a hypothesis explaining the placement of so many non-evidenced based ICDs.  The authors concluded that non-electrophysiologist are less likely to be aware of the evidence although they could not rule out financial incentive as a possible factor.

 But not all is bad press in the land of cardiology.  Published in the New England Journal of Medicine, the EMPHASIS-HF study showed that eplerenone reduced the risk of death and hospitalization amongst patients with Class II heart failure with an EF <35% [7].  These results come from the same group that produced the seminal RALES study which demonstrated that spironolactone reduced mortality and hospital readmission for patient with class III/IV heart failure as well as the EPHESUS study which showed that eplerenone reduced morbidity and mortality amongst patients with recent MI and LV dysfunction. The recent EMPHASIS-HF study randomized 2737 patients to either eplerenone or placebo.  Patients were included in the study if they were at least 55 years, had NYHA functional class II symptoms, an ejection fraction £30%, and were on treatment with a beta-blocker, angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) at the recommended or maximal tolerated dose.  The primary outcome was a composite of death from cardiovascular causes or a first hospitalization for heart failure.  The primary outcome occurred in 18.3% of patients in the eplerenone group compared to 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001). 12.5% of patient receiving eplerenone died compared to 15.5% receiving placebo (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P = 0.008) while 29.9% of patients in the eplerenone group were hospitalized for any reason compared to 35.8% of placebo group (hazard ratio, 0.77; 95% CI, 0.67 to 0.88; P<0.001). Death and hospitalization secondary to cardiac causes were also significantly lower in the eplerenone group.  The benefits of eplerenone, an aldosterone antagonist, in cardiovascular morbidity and mortality were once again clearly demonstrated in this study.   Presumably spironolactone, a cheaper aldosterone antagonist with more side effects, has a similar effect, but head to head comparisons are not yet available.

 This Primecuts edition has touched on aspects of our practice we can improve on and has given us some concrete recommendations for future patient care.  While we may have some difficulties with self-improvement (when did you say you were going to the gym?), let’s hope being a better evidenced-based doctor comes a little easier.

Dr. Scott is a first year resident at NYU Langone Medical Center

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

References: 

1. Pear R. US alters rule on paying for end-of-life planning. New York Times (New York Ed). 2011 Jan 04:Health: A15. http://www.nytimes.com/2011/01/05/health/policy/05health.html?ref=health

 2. Sanders A, Schepp M, Baird M. Partial do-not-resuscitate orders: A hazard to patient safety and clinical outcomes. Crit Care Med. 2011:39(1):14-18.

3. Clifton G, Valadka A, Zygun D, Coffey C, Drever P, Fourwinds S, Janis L, Wilde E, Taylor P, Harshman K, Conley A, Puccio A, Levin H, McCauley S, Bucholz R, Smith K, Schmidt J, Scott J, Yonas H, Okonkwo D. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomized trial. Lancet Neurology. 2010 Dec 20. Available from http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(10)70300-8/fulltext

 4. Grady D. Many Defibrillators Implanted Unnecessarily, Study Says. New York Times (New York Ed). 2011 Jan 5:Health: A12.  http://www.nytimes.com/2011/01/05/health/05device.html?ref=health

 5. Al-Khatib S, Hellkamp A, Curtis J, Mark D, Peterson E, Sanders G, Heidenreich P, Hernandez A, Curtis L, Hammill S. Non-Evidenced-Based ICD Implantations in the United States. JAMA. 2011 Jan 5:305(1):43-49.  http://jama.ama-assn.org/content/305/1/43.full

 6. Epstein A, DiMarco J, Ellenbogen K, Estes N, Freedman R, Gettes L, Gillinov A, Gregoratos G, Hammill S, Hayes D, Hlatky M, Newby L, Page R, Schoenfeld M, Silka M, Stevenson L, Sweeney M, Smith S, Jacobs A, Adams C, Anderson J, Buller C, Creager M, Ettinger S, Faxon D, Halperin J, Hiratzka L, Hunt S, Krumholz H, Kushner F, Lytle B, Nishimura R, Ornato J, Page R, Riegel B, Tarkington L, Yancy C. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008 May 27:51(21):e1-62.  http://content.onlinejacc.org/cgi/content/full/j.jacc.2008.02.032

 7. Zannad F, McMurray J, Krum H, van Veldhuisen D, Swedberg K, Shi H, Vincent J, Pocock S, Pitt B. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. NEJM. 2011 Jan 6:364(1):11-21.  http://www.nejm.org/doi/full/10.1056/NEJMoa1009492

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