Primecuts – This Week In The Journals

May 23, 2016

PrimeCuts 7 min read

1280px-Flip_flops_-_just_pick_one_upBy Priya Patel, MD

Peer Reviewed

This last week, ISIS had a number of terrorist attacks, confirming a shift from traditional battlefield tactics back to targeted attacks seen prior to 2014. They confirmed their role in the bombings at a gas plant in Baghdad which killed 10 and injured 24 [1]. Just days prior to this, 66 were killed in a bombing in a Baghdad food market and 87 others were injured [2].

In the U.S., even more attention has been turned towards likely Republican candidate Donald Trump as the presidential primaries are coming to an end. The New York Times sparked a nationwide exploration into his past relationships with women in his professional and private life when they wrote an in-depth exposé on these relationships over the past 40 years, characterized by “unwelcome romantic advances, unending commentary on the female form, a shrewd reliance on ambitious women, and unsettling workplace conduct.” [3]

Now, moving on to the latest news in medicine. 

Tocilizumab, the next new treatment for giant cell arteritis. 

Tocilizumab, a monoclonal antibody that acts against the interleukin-6 receptor, was looked at as a novel therapy for giant cell arteritis (GCA) in a recent paper published in the Lancet. IL-6 induces acute phase responses and has been implicated in the pathogenesis of GCA. IL-6 concentrations have been shown to be higher in all layers of medium and large-sized vessels in patients with GCA, and these levels may increase during flares and decrease with treatment with steroids [4]. Villeger et al. conducted the first randomized, placebo-controlled trial to study the efficacy and safety of tocilizumab in patients with newly diagnosed or recurrent GCA [5]. A total of 30 patients were randomly assigned in a 2:1 fashion to either treatment of intravenous tocilizumab every 4 weeks for 1 year + oral prednisolone with tapering, or placebo + oral prednisolone with tapering. The primary endpoint of remission at 12 weeks of treatment (meaning normal ESR and CRP and the absence of symptoms on low dose prednisolone of 0.1mg/kg/day) occurred in 85% of the intervention group compared to 40% of the placebo group (risk difference 45%, 95% CI 11–79; p=0.0301).  Additionally, 85% of patients in the intervention group maintained remission at the end of the year compared to just 20% in the placebo group (risk difference 65%, 95% CI 36–94; p=0.0010). While the standard therapy, steroids, is widely accepted, the side effects of long-term corticosteroid use are well-known and include osteoporosis, joint necrosis, and adrenal insufficiency [6]. Tocilizumab could be a great alternative to avoid these side effects and help patients maintain remission if future studies confirm these findings.

Does cardiac index really influence renal function in heart failure patients? 

Decreased renal function in hospitalized heart failure patients has long been attributed to a low cardiac index (CI). However, recent studies have challenged this idea by demonstrating a lack of correlation between cardiac output and renal function. Several recent studies have even showed paradoxical correlations between cardiac output and renal function. The ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial was a randomized trial evaluating the use of pulmonary artery catheterization in patients hospitalized with heart failure [7]. Hanberg et al. analyzed data from this large trial, including patients either randomized to the PAC arm of the ESCAPE trial, or enrolled in the PAC registry of the ESCAPE trial, to study the relationship between CI and renal function in patients with decompensated heart failure [8]. Of note, patients included were mostly white males in their 50s-60s. The authors did not find statistically significant associations supporting the idea that low cardiac output is an important drive for renal dysfunction in this population.  Further breakdown of these patients into those with co-morbidities such as diabetes and hypertension, those with EF >40%, and those receiving classic heart failure medications such as loop diuretics, beta-blockers and ace inhibitors still did not show a relationship between CI and renal function. One of the major limitations of this study is the limitation of evaluating kidney function via creatinine and estimated GFR.  Also, the etiology of kidney disease in these patients at baseline is unknown. Nonetheless, the lack of relationship found between cardiac and kidney function supports the concept that decreased renal function in patients hospitalized with heart failure may not be attributed to a low CI. Instead there may be other factors that directly influence renal function, such as neurohormonal systems.

Mortality benefit of statins sustained through extended follow-up. 

Statins have become standard treatment in those with cardiovascular disease. However, there is controversy over longer term use of statins, particularly due to concern for increased cancer incidence [9, 10]. In an extended follow-up of the LIPID study, researchers evaluated all-cause mortality, cause-specific mortality and new cancer diagnoses in the 7721 of the original 9014 patients evaluated in the LIPID study [11,12]. The original LIPID study was a double-blind, randomized trial of 9014 patients with coronary artery disease treated with pravastatin 40mg daily versus placebo over 6 years looking at mortality from CAD [11]. Initially after the 6-year double-blind period, the study showed a statistically significant decrease in all-cause, cardiovascular and coronary heart disease-related mortality in the pravastatin group. Given the mortality benefit in the LIPID trial, all participants (regardless of original randomization group) were offered statin therapy, and 88% of those in the statin group and 86% of those in the placebo group were started on a statin. During extended follow-up over 10 years, patients who had been assigned pravastatin maintained a significantly lower risk of death from CHD, from cardiovascular disease, and from any cause [12]. There were no significant differences in mortality from cancer or in the incidence of organ-specific cancers between the groups. Overall, this study further validates the efficacy of statins and does not support an association of long-term statin use with cancer.

Amiodarone and Lidocaine could play a role in out-of-hospital cardiac arrest. 

Antiarrhythmic agents including lidocaine and amiodarone are frequent drugs of choice in the setting of shock-refractory ventricular fibrillation or pulseless ventricular tachycardia in patients presenting with cardiac arrest in the field. Earlier studies have shown that patients who received amiodarone in this setting were more likely to have return to spontaneous circulation and survive to be admitted to the hospital. In a recent study, Kudenchuk et al. explored the effects of survival and neurologic outcome in 3026 patients with out of hospital cardiac arrest with ventricular fibrillations or pulseless ventricular tachycardia unresponsive to defibrillation at ten different North American sites [13]. Participants were randomized to receive amiodarone, lidocaine or placebo after failing standard of care treatment of defibrillation.  In the per-protocol analysis, 24.4% of patients in the amiodarone group survived to hospital discharge, compared to 23.7% of patients in the lidocaine group, and 21.0% of patients who received placebo. The absolute risk difference for the primary comparison of amiodarone versus placebo was 3.2 percentage points (95% CI,-0.4 to 7.0; p=0.08). The rates of survival with a favorable neurologic outcome were similar in all of the groups. Of note, there was heterogeneity of treatment effect with respect to whether or not the arrest was witnessed (p=0.05). There was a statistically significant difference between the survival rates of patients who received amiodarone versus placebo, and for lidocaine versus placebo, but not for amiodarone versus lidocaine. This may indicate that amiodarone and lidocaine are both effective medications for refractory pulseless ventricular tachycardia and ventricular fibrillation after cardiac arrest, but the timing of the treatment is key.

Mini-cuts:

An adjusted one-dose administration of the oral cholera vaccine prequalified by the WHO, rather than the standard two dose regimen, was protective in residents of Dhaka, Bangladesh, a highly endemic area [14].

NYU’s own investigators led by Dr. Bangalore explored the benefit of coronary artery bypass graft (CABG) vs percutaneous coronary intervention (PCI) in patients with multi-vessel coronary disease and systolic dysfunction and found that both groups had similar primary outcomes of long-term survival. PCI was associated with higher risk of associated with risk of MI and repeat revascularization, and CABG was associated with higher risk of stroke [15].

A recent article in Chest performed a large cohort analysis of patients with fibrotic interstitial lung disease hospitalized at one institution over 3 years with acute respiratory worsening for any reason and found that they had a statistically significant increase in in-hospital and post-discharge mortality [16].

Dr. Priya Patel is a resident at NYU Langone Medical Center 

Peer reviewed by Karin Katz, M.D., Chief Resident, Internal Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References: 

  1. http://www.cnn.com/2016/05/15/middleeast/iraq-violence-isis/index.html
  2. http://www.nytimes.com/2016/05/12/world/middleeast/baghdad-market-bomb-isis.html 
  3. http://www.nytimes.com/2016/05/15/us/politics/donald-trump-women.html?_r=0 
  4. Emilie D, Liozon E, Crevon MC, et al. Production of interleukin 6 by granulomas of giant cell arteritis.Human Immunology. 1994;39(1):17–24.
  5. Villiger PM et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: A phase 2, randomised, double-blind, placebo-controlled trial. Lancet 2016 Mar 4.  http://www.sciencedirect.com/science/article/pii/S0140673616005602
  6. Buchman A. L. Side effects of corticosteroid therapy: Inflammatory bowel disease. J. Clin. Gastroenterol. 33, 289–294 (2001). http://journals.lww.com/jcge/Abstract/2001/10000/Side_Effects_of_Corticosteroid_Therapy.6.aspx
  7. Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA 2005;294:1625–33.
  8. Hanberg JS et al. Reduced Cardiac Index Is Not the Dominant Driver of Renal Dysfunction in Heart Failure. Journal of the American College of Cardiology, 2016; 67(19)2199-2208. http://m.amedeo.com/27173030
  9. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–1278. doi:10.1016/S0140-6736(05)67394-1 http://www.ctsu.ox.ac.uk/research/meta-trials/ctt/ctt-website
  10. Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G. Statins and the risk of colorectal cancer. N Engl J Med. 2005;352:2184–2192.
  11. LIPID Study Group, Tonkin A, Simes RJ. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1347–1357
  12. Hague WE et al. Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: Sixteen Years of Follow-Up of the LIPID Study. Circulation. 2016; 133:1851-1860.  http://www.mdlinx.com/cardiology/medical-news-article/2016/05/11/coronary-heart-disease-cardiovascular-diseases-cholesterol/6667461/
  13. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med 2016;374:1711-1722. http://www.nejm.org/doi/full/10.1056/NEJMoa1514204
  14. Qadri F et al. Efficacy of a single-dose, inactivated oral cholera vaccine in Bangladesh. N Engl J Med 2016 May 5; 374:1723.
  15. Bangalore, Sripal; Guo, Yu; Samadashvili, Zaza; Blecker, Saul; Hannan, Edward L. Revascularization in Patients with Multivessel Coronary Artery Disease and Severe Left Ventricular Systolic Dysfunction: Everolimus Eluting Stents vs. Coronary Artery Bypass Graft Surgery. Circulation. 2016 May 5;:?-? (2101292) http://circ.ahajournals.org/content/early/2016/05/04/CIRCULATIONAHA.115.021168.short?rss=1
  16. Moua T, Westerly BD, Dulohery MM, Daniels CE, Ryu JH, Lim KG. Patients With Fibrotic Interstitial Lung Disease Hospitalized For Acute Respiratory Worsening: A Large Cohort Analysis. Chest. 2016;149(5):1205-1214. http://journal.publications.chestnet.org/article.aspx?articleid=2481791