Digitalis Therapy in Heart Disease: Less is More?
Digoxin (from the foxglove plant, digitalis) , an inexpensive and old drug used in heart disease, is back in the news (1, 2, 3). Compelling evidence from recent studies show its benefic effects in the treatment of heart failure and in prevention of acute coronary syndromes.
The Digitalis Investigation Trial (DIG), published in 1997, showed that digoxin did not increase survival but did help to keep patients with congestive heart failure out of Hospital.
However, Rathore et al, on a post hoc analysis of data from The Digitalis Investigation Trial (DIG), dividing the man treated into three groups according to their blood digoxin concentration after one month of treatment: 0.5-0.8 ng/ml, 0.9-1.1 ng/ml and > 1.2 ng/ml, found that mortality in men in the lowest level group was 6.3% lower than that of men in the placebo group. In contrast, mortality in men in the intermediate and highest level groups was 2.6% and 11.8% higher respectively than that of the placebo group (4).
Also, Gheorghiade M et al, in another retrospective analysis of data from the DIG trial have indicated a beneficial effect of digoxin on morbidity and no excess mortality in women at serum concentrations from 0.5 to 0.9 ng/ml, whereas serum concentrations > or =1.2 ng/ml seemed harmful (5).
So, additional benefits in patients with congestive heart failure were not seen at higher doses traditionally considered to be therapeutic (with serum concentrations of 1.0 to 1.5 ng/ml). The higher doses may predispose to arrhythmias and to increase the mortality risk.
Leor J and colleagues in 1995 found in patients recovering from myocardial infarction that one year mortality was significantly higher among patients treated with a full dose [19 of 112 (17%)] than patients treated with a low dose of digoxin [1 of 41 (2%)] (6)
Quintiliano de Mesquita and Claudio Baptista found in patients that suffered myocardial infarction, treated with relatively low dosages of different cardiac glycosides, a global mortality of just 1.4% per year. The global mortality for the patients without previous myocardial infarction was 14.2% (0.5% per year). This case study involved 1150 patients with stable coronary heart disease. The follow-up period was 28 years. The cardiac glycosides employed were: Digitoxin, Digoxin, Acetyldigoxin, Betametyldigoxin, Proscillaridin-A or Lanatoside-C at daily therapeutic oral doses - nontoxic, preferably lower. These doctors from Brazil started in 1996 to prescribe even lower doses of digitalis to old patients, with no clinical signs of coronary heart disease, considering the heart of these patients as vulnerable (7, 8, 9).
P.S.: Digoxin treatment at low doses (<_ 0.125 mg/d) is likely to result in low serum concentrations (0.5 - 09 ng/ml)
1. Digitalis Safe In Patients With Common Form Of Heart Failure, Study Shows, Medical News Today, July 28, 2006 at http://www.medicalnewstoday.com/medicalnews.php?newsid=48086
2. Digitalis Safe In Patients With Common Form Of Heart Failure, Medical News Today, August 27, 2006 at http://www.medicalnewstoday.com/medicalnews.php?newsid=50551
3. Digoxin Can Reduce Mortality And Hospitalization In Heart Failure, Medical News Today, Dec 13, 2005 at http://www.medicalnewstoday.com/medicalnews.php?newsid=34894
4. Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM, Association of serum digoxin concentration and outcomes in patients with heart failure, JAMA. 2003;289:871-878 http://tinyurl.com/c7os3
5. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis, Adams KF Jr, Patterson JH, Gattis WA, O Connor CM, Lee CR, Schwartz TA, Gheorghiade M., J Am Coll Cardiol. 2005 Aug 2;46(3):497-504 http://tinyurl.com/8ppnp
6. Leor J, Goldbourt U et al. Digoxin and increased mortality among patients recovering from acute myocardial infarction: importance of digoxin dose, Cardiovasc Drugs Ther 1995 Oct;9(5):723-9 http://tinyurl.com/ao6ld
7. Cardiotonico: Insuperavel na Preservacao da Estabilidade Miocardica como Preventivo das Sindromes Coronarias Agudas e Responsavel pela Prolongada Sobrevida--Casuistica de 28 anos (1972-2000), Mesquita, QHde e Baptista, CAS. Ars Cvrandi. May 2002, Volume 35, republished in 2005 at http://www.infarctcombat.org/28anos/digitalicos.html, with summary in English at http://www.infarctcombat.org/heartnews-16.html.
8. Coracao do Idoso, Aparentemente Normal, Deve ser Considerado Vulneravel, Chapter from the book “Remedio Boicotado Substitui Ponte de Safena", Mesquita, QHde, 1996 http://www.infarctcombat.org/idoso/qhm.html
9. Two Heart Disease Theories, Same Therapeutic Treatment. Published in Dr. Thomas Cowan's Newsletter, Dec 2005 at http://www.fourfoldhealing.com/NL%20NovDec%202005.htm
10. The underuse of digoxin in heart failure, and approaches to appropriate use, Ali Ahmed, James B. Young, Mihai Gheorghiade. CMAJ, February 27, 2007; 176(5): 641 at http://tinyurl.com/2ovqun
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