Bleeding from ruptured esophageal varices is the main complication of portal hypertension and a major cause of death. About one-third of variceal bleeding episodes are fatal while 70% of survivors re-bleed within a year. Propranolol, the drug of choice for primary prevention of variceal bleeding, has been found to be effective in 45% of patients who have never bled, and in only 40% of patients who have had a bleeding episode before. Thus, this drug does not protect a significant number of patients and combination therapy has been advocated as a result. Various drug combinations have been tried, most commonly propranolol with isosorbide mononitrate. However, the problem with combination therapy is an increased incidence of side effects, poor tolerability and lack of compliance. The search for an ideal drug combination that is effective, relatively free from side effects and easy to administer, has been elusive.
Spironolactone, a drug commonly used in cirrhotics with ascites to reduce fluid overload, has been found to have an independent portal hypotensive effect. This drug has been in use for a long period of time and has been found to be safe and free of side effects, except for occasional gynaecomastia.
This study, performed by a team lead by Professor Binay K. De, is described in a research article published in the World Journal of Gastroenterology. In the authors' view, the combination of spironolactone with propranolol scores over other combinations for variceal re-bleed, because of the different mechanisms of action of the two drugs and some of the unique properties of spironolactone.
Spironolactone has a direct portal hypotensive effect in addition to its ability to reduce plasma volume by diuresis. Spironolactone has a direct effect on the vasculature and suppressive effect on immunoactive and inflammatory cytokines, independent of its anti-aldosterone effect. An antifibrotic property has also been evidenced experimentally in rats. Because it is a long acting drug, a single daily dosage will suffice.
Using a rational study design, portal pressure was measured after hemodynamic stabilization of the patients. The drugs were administered and the effects were re-assessed on day eight. This allowed time for stabilization of drug levels in the plasma and also provided us information on the early portal hemodynamic changes following drug administration, because the maximal risk of re-bleeding is during the first two weeks.
However, further research using a larger number of patients with a long term follow up is warranted before declaring this combination to be the choice of treatment in preventing variceal re-bleeding.
Reference: De BK, Dutta D, Som R, Biswas PK, Pal SK, Biswas A. Hemodynamic effects of propranolol with spironolactone in patients with variceal bleed: A randomized controlled trial. World J Gastroenterol 2008; 14(12): 1908-1913 wjgnet/1007-9327/14/1908.asp
Correspondence to: Binay K De, Department of Medicine, Medical College, 64/4A/1A Dr. Suresh Chandra Banerjee Road, Calcutta 700010, India.
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
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The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Jing Zhu
World Journal of Gastroenterology