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Southwest Pulmonary and Critical Care Fellowships
In Memoriam

Pulmonary Journal Club

(Click on title to be directed to posting, most recent listed first)

May 2017 Phoenix Pulmonary/Critical Care Journal Club
October 2015 Phoenix Pulmonary Journal Club: Lung Volume Reduction
September 2015 Tucson Pulmonary Journal Club: Genomic Classifier
   for Lung Cancer
April 2015 Phoenix Pulmonary Journal Club: Endo-Bronchial Ultrasound in
   Diagnosing Tuberculosis
February 2015 Tucson Pulmonary Journal Club: Fibrinolysis for PE
January 2015 Tucson Pulmonary Journal Club: Withdrawal of Inhaled
    Glucocorticoids in COPD
January 2015 Phoenix Pulmonary Journal Club: Noninvasive Ventilation In 
   Acute Respiratory Failure
September 2014 Tucson Pulmonary Journal Club: PANTHEON Study
June 2014 Tucson Pulmonary Journal Club: Pirfenidone in Idiopathic
   Pulmonary Fibrosis
September 2014 Phoenix Pulmonary Journal Club: Inhaled Antibiotics
August 2014 Phoenix Pulmonary Journal Club: The Use of Macrolide
   Antibiotics in Chronic Respiratory Disease
June 2014 Phoenix Pulmonary Journal Club: New Therapies for IPF
   and EBUS in Sarcoidosis
March 2014 Phoenix Pulmonary Journal Club: Palliative Care
February 2014 Phoenix Pulmonary Journal Club: Smoking Cessation
January 2014 Pulmonary Journal Club: Interventional Guidelines
December 2013 Tucson Pulmonary Journal Club: Hypothermia
December 2013 Phoenix Pulmonary Journal Club: Lung Cancer
   Screening
November 2013 Tucson Pulmonary Journal Club: Macitentan
November 2013 Phoenix Pulmonary Journal Club: Pleural Catheter
   Infection
October 2013 Tucson Pulmonary Journal Club: Tiotropium Respimat 
October 2013 Pulmonary Journal Club: Pulmonary Artery
   Hypertension
September 2013 Pulmonary Journal Club: Riociguat; Pay the Doctor
August 2013 Pulmonary Journal Club: Pneumococcal Vaccine
   Déjà Vu
July 2013 Pulmonary Journal Club
June 2013 Pulmonary Journal Club
May 2013 Pulmonary Journal Club
March 2013 Pulmonary Journal Club
February 2013 Pulmonary Journal Club
January 2013 Pulmonary Journal Club
December 2012 Pulmonary Journal Club
November 2012 Pulmonary Journal Club
October 2012 Pulmonary Journal Club
September 2012 Pulmonary Journal Club
August 2012 Pulmonary Journal Club
June 2012 Pulmonary Journal Club
June 2012 Pulmonary Journal Club
May 2012 Pulmonary Journal Club
April 2012 Pulmonary Journal Club
March 2012 Pulmonary Journal Club
February 2012 Pulmonary Journal Club
January 2012 Pulmonary Journal Club
December 2011 Pulmonary/Sleep Journal Club
October, 2011 Pulmonary Journal Club
September, 2011 Pulmonary Journal Club
August, 2011 Pulmonary Journal Club
July 2011 Pulmonary Journal Club
May, 2011 Pulmonary Journal Club
April, 2011 Pulmonary Journal Club
February 2011 Pulmonary Journal Club 
January 2011 Pulmonary Journal Club 
December 2010 Pulmonary Journal Club

 

Both the Phoenix Good Samaritan/VA and the Tucson University of Arizona fellows previously had a periodic pulmonary journal club in which current or classic pulmonary articles were reviewed and discussed. A brief summary was written of each discussion describing thearticle and the strengths and weaknesses of each article.

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Entries in SERAPHIN (1)

Monday
Dec162013

November 2013 Tucson Pulmonary Journal Club: Macitentan

Pulido T, Adzerikho I, Channick RN, Delcroix M, Galiè N, Ghofrani HA, Jansa P, Jing ZC, Le Brun FO, Mehta S, Mittelholzer CM, Perchenet L, Sastry BK, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau G; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809-18. [CrossRef] [PubMed]

Treatment of pulmonary arterial hypertension (PAH) with endothelin receptor antagonists (ERA) has been shown to improve exercise capacity and functional status, but not mortality. A recent systematic review found uncertainty regarding ERAs’ effects on mortality (1). Macitentan, a new molecule structurally similar to bosentan, targets endothelin-A and endothelin-B receptors, offers greater tissue penetration, and has more sustained receptor binding.

SERAPHIN was an industry-sponsored, double-blinded, randomized controlled trial which examined the effect of long-term macitentan use on PAH morbidity and mortality. Between May 2008 and December 2009, 742 patients in 39 countries were randomized to placebo, macitentan 3 mg daily, or macitentan 10 mg daily. Participants had to be ≥12 years of age with Group 1 PAH confirmed by right heart catheterization and have WHO functional class II, III, or IV heart failure. Participants taking intravenous or subcutaneous prostanoids were excluded, but other concomitant treatments were allowed. The composite endpoint of worsening of PAH (initiation of intravenous or subcutaneous prostanoids, lung transplantation, or atrial septostomy) or death from any cause was the primary endpoint. Secondary outcomes included the composite outcome of hospitalization or death due to PAH, change in 6-minute walk (6MW), improvement in WHO functional class, and adverse events.

As compared to placebo, both the 3 mg and 10 mg daily dose of macitentan were found to reduce the composite endpoint of worsening PAH or death with hazard ratios of 0.70 (CI 95% 0.52-0.96) and 0.55 (CI 95% 0.32-0.76), respectively. Both also improved the composite endpoint of hospitalization or death due to PAH, 6MW and WHO functional class. The proportions of participants with elevated liver enzymes were comparable across the 3 groups (1-5%); however, participants in the 3 mg and 10 mg macitentan groups were more likely to experience anemia, 8.8% and 13.2%, respectively, than the 3.2% of participants in the placebo group.

Treatment with macitentan significantly decreased the composite endpoint of worsening PAH or death. The major driver of this reduction was fewer instances of worsening of PAH rather than fewer deaths. Similar to previous trials, SERAPHIN fails to clearly demonstrate that ERA use reduces all cause or PAH-specific mortality. While macitentan use did appear to result in meaningful reductions in symptom burden and hospitalization, the effect on 6MW is smaller than that previously reported for other ERAs (1). Macitentan use does appear to be safe with a slightly higher risk of anemia being observed. The incremental benefit of macitentan over existing treatments is unknown.

Candy Wong, MD; Cristine Berry, MD; Joe Gerald, PhD

University of Arizona

Tucson, AZ

Reference

  1. Liu C, Chen J, Gao Y, Deng B, Liu K. Endothelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD004434. DOI: 10.1002/14651858.CD004434.pub5. [CrossRef] [PubMed]

Reference as: Wong C, Berry C, Gerald J. November 2013 Tucson pulmonary journal club: macitentan. Southwest J Pulm Crit Care. 2013;7(6):349-50. doi: http://dx.doi.org/10.13175/swjpcc174-13 PDF