title: Clinical efficacy of water extract of stem bark of Terminalia arjuna (Roxb. ex DC.) Wight & Arn. in patients of chronic heart failure: a double-blind, randomized controlled trial.
abstract: BACKGROUND
  The stem bark of Terminalia arjuna (Roxb. ex DC.) Wight and Arn. (Arjuna) is used in Indian system of medicine (Ayurveda) for treatment of various cardiac diseases, including heart failure. However, well designed clinical trials exploring its efficacy and safety in chronic heart failure (CHF) are lacking.
  
  
  OBJECTIVE
  To ascertain the add-on efficacy and safety of a standardized water extract of stem bark of Arjuna (Arjuna extract) in CHF patients on standard pharmacotherapy.
  
  
  METHODS
  Double-blind, parallel, randomized, placebo-controlled add-on clinical trial.
  
  
  METHODS
  After approval of institutional ethics committee, 100 patients of CHF of New York Heart Association (NYHA) functional class II on standard pharmacotherapy having an echocardiographic left ventricular ejection fraction (LVEF) ≤ 40% were consecutively recruited with informed consent and randomized 1:1 to Arjuna extract 750 mg or matching placebo twice daily. The primary outcome measure was change in LVEF at 12 weeks. Secondary outcome measures included changes in (i) NYHA functional class, (ii) distance covered in 6 min walk test (6MWT), (iii) quality of life (QoL), as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ), (iv) plasma brain natriuretic peptide, (v) plasma cytokines (interleukin-6, high sensitivity C-reactive protein and tumour necrosis factor-α) and (vi) oxidative stress markers [serum thiobarbituric acid reactive substances (TBARS), red blood cell (RBC) superoxide dismutase (SOD), RBC catalase and RBC glutathione (GSH)] at 6 and 12 weeks. Safety assessment was done by adverse event monitoring and laboratory investigations. Results were expressed as mean ± SD or median (interquartile range) and analysed with intention-to- treat principle using appropriate two-sided statistical tests. A p-value < 0.05 was considered significant.
  
  
  RESULTS
  Arjuna extract was well-tolerated, but did not change LVEF (24.3 ± 7.1 versus 25.5 ± 7.7%; p = 0.4) or secondary outcome measures except preservation of RBC catalase activity [1275(104, 10350) versus 1243.5(104, 10350) U/g haemoglobin; p = 0.01] compared to placebo. Significantly greater percentage increases occurred in distance covered in 6 MWT, RBC-SOD, RBC catalase, RBC GSH and in symptom severity and stability domains of KCCQ in patients on Arjuna extract versus those on placebo, on a post-hoc analysis, between subgroups of patients who improved in these outcomes.
  
  
  CONCLUSIONS
  Arjuna extract did not improve LVEF in CHF patients over 12 weeks, although there was improvement in functional capacity, antioxidant reserves and symptom-related QoL domains in some patients.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029 New Delhi, India.. Electronic address: skmaulik@aiims.ac.in.
authors.forename: Subir K
authors.initials: SK
authors.lastname: Maulik
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029 New Delhi, India.; Department of Pharmacology, Sree Gokulam Medical College & Research Foundation, Venjaramoodu, Trivandrum, 695607 Kerala, India.
authors.forename: Vinu
authors.initials: V
authors.lastname: Wilson
authors.affiliation: Department of Cardiology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029 New Delhi, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Seth
authors.affiliation: Department of Cardiology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029 New Delhi, India.
authors.forename: Balram
authors.initials: B
authors.lastname: Bhargava
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029 New Delhi, India.
authors.forename: Pamila
authors.initials: P
authors.lastname: Dua
authors.affiliation: Department of Cardiology, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, 110029 New Delhi, India.
authors.forename: Sivasubramanian
authors.initials: S
authors.lastname: Ramakrishnan
authors.affiliation: Dabur India Limited, Ghaziabad, 201010 Uttar Pradesh, India.; Emami Limited, Kolkata, 700107 West Bengal, India.
authors.forename: Chandra K
authors.initials: CK
authors.lastname: Katiyar
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007194:India; D008297:Male; D008515:Medicine, Ayurvedic; D008875:Middle Aged; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D018547:Plant Stems / Q000737:chemistry; D011788:Quality of Life; D029766:Terminalia / Q000737:chemistry; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents
keywords: Arjuna; Ayurveda; Cardiac failure; Cardiovascular disease; Herbal drug; Terminalia arjuna