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2-7 THE EFFECT OF DIGOXIN ON MORTALITY AND
MORBIDITY IN PATIENTS WITH HEART FAILURE
Digoxin had no effect on overall mortality. It reduced
the number of hospitalizations. The reduction in death or
hospitalization for worsening HF was greatest in patients
with ejection fractions < 0.25, those with enlarged
hearts, and those with class III and IV HF. NEJM February
20, 1997: 336: 525-33.2-7 THE EFFECT OF DIGOXIN ON MORTALITY AND
MORBIDITY IN PATIENTS WITH HEART FAILURE
"Although digoxin is one of the most commonly
prescribed drugs for the treatment of heart failure (HF),
there is uncertainty about its long-term efficacy and
safety." The long-term effect of digoxin on
mortality and hospitalization for HF is unknown. This
study was designed to evaluate the long-term effects.
Conclusion: Digoxin did not reduce overall mortality; it
reduced the rate of hospitalization.
STUDY
- 1. Randomized
(double-blind) 7000 patients (mean age 63) to
digoxin or placebo.
- 2. All had left
ventricular ejection fractions under 0.45.
- 3. All received
diuretics and/or angiotensin converting enzyme
inhibitors.
- 4. Follow up —3
years.
RESULTS
- Overall mortality:
digoxin group —35%; placebo group —
35%.
- In the digoxin group
there was a trend toward a decreased risk of
death attributed to worsening HF (risk ratio
— 0.88). This was offset by an increase in
other cardiac causes of death (presumed
arrhythmia, coronary artery disease,
bradyarrhythmias, and cardiac surgery).
- Hospitalizations:
digoxin group — 6 % fewer than
placebo-group; hospitalizations for worsening HF
— 8% fewer.
- No difference in risk
of hospitalizations for ventricular arrhythmia
and cardiac arrest.
- Suspected
"digitalis" toxicity: 12% digoxin
group; 9% in placebo group.
DISCUSSION
- In this study,
patients with left ventricular ejection fractions
of 0.45 or less, digoxin when added to ACE
inhibitors and diuretics had no effect on overall
mortality. There were fewer deaths due to
worsening heart failure and more deaths from
other cardiac causes.
- Rate of
hospitalization for worsening HF was less in the
digoxin group. (Other studies have also found
that worsening HF and hospitalizations occurred
less often in patients treated with digoxin.)
- The study included a
wide spectrum of patients with HF with diverse
causes and a broad range of symptoms (31% class
III).
- At the median dose of
0.25 mg digoxin daily, few patients were
hospitalized for toxicity. The great majority had
serum digoxin within normal limits.
- The reduction in
death or hospitalization for worsening HF was
greatest in patients with ejection fractions <
0.25, those with enlarged hearts, and those with
class III and IV HF.
CONCLUSION
Digoxin had no effect on overall mortality. It reduced
the number of hospitalizations.
NEJM February 20,
1997: 336: 525-33. Original investigation from the
Digitalis Investigation Group.
See editorial: "End
of the Oldest Controversy in Medicine. Are We Ready to
Conclude the Debate on Digitalis?’ NEJM February 20,
1997; 336: 575-76.: "For most patients with heart
failure, digitalis remains an effective, safe and
inexpensive choice for the relief of symptoms, despite
its inability to alter the natural history of the
disease. To the extent that symptom relief has driven
most of the drug’s clinical use, the results of the
trial should not lead most physicians to change their
prescribing patterns."
But the trial "...changes one fundamental aspect of
the treatment of heart failure: digoxin’s inability
to substantially influence morbidity and mortality
eliminates any ethical mandate for its use and
effectively relegates it to be prescribed for treatment
of persistent symptoms after the administration of drugs
that do reduce the risk of death and hospitalization
(such as angiotensin-converting- enzyme inhibitors and
beta-adrenergic blockers). As the list of such drugs
increases in the coming years, the use of digoxin will
gradually, but inevitably, diminish."
Comment:
Heart failure is a deadly condition. In this large study
of persons, mean age 63, one third were dead in 3 years
despite the best available treatment.
I believe the fact that digoxin reduced the rate of
hospitalizations, and thus improved quality of life, is a
recommendation for its use.
This study added digoxin to ACE inhibitors and diuretics.
It did not compare digoxin alone with placebo. In many
parts of the world the more expensive drugs are not
available. Digoxin will remain a mainstay of therapy.
Interesting side note: A short article in The Charlotte
Observer recently reported that the FDA has finally
approved Lanoxin for use. Lanoxin was introduced in the
US in 1934, before passage of the Food, Drug, and
Cosmetic Act (1938). A few years ago, the FDA asked
Glaxco-Wellcome to file a new drug application to set
pharmacological standards for makers of generic drugs.
Lanoxin remains the gold standard. RTJ
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