Download Use of digoxin in older patients

Gerontologija 2010; 11(2): 120–123
GERONTOLOGIJA
Theory and practice
Use of digoxin in older patients
V. Lesauskaitė, T. Jankauskas
Geriatric Clinic, Kaunas University of Medicine
Abstract
In the treatment of worsening of systolic heart failure important role maintains digoxin. In the management of older patients it is important to take into account age-related changes
of pharmacokinetics and pharmacodynamics, decreased glomerular filtration rate, sex and concomitant diseases. Older individuals have lower tolerance of digitalis than younger. They
have increased risk of digitalis toxicity. Digitalis Investigation
Group clinical study has proven that in patients aged 65 years
and older only small serum digoxin concentration (0.5–0.9 ng/
mL) is related to reduce in all cause mortality. The recommended daily dose of digoxin for these patients is 0.125 mg per day.
Digoxin could be administered to all patients with heavy heart
failure and decreased systolic function together with ACE inhibitors, beta blockers, spironoilactone, diuretics. Thus, the role
of digoxin in treatment of heart failure remains secondary.
Keywords:
older patients, digoxin toxicity, daily dose of digoxin
Treatment of chronic heart failure (HF) has rapidly
progressed during last 20 years. Big randomized clinical
studies have shown benefit of suppression of renin-angiotensin-aldesteron and sympathic nervous systems. Heart
Address: prof. habil. dr. Vita Lesauskaitė
Kauno medicinos universiteto Geriatrijos klinika
A. Mickevičiaus 9, Kaunas
E-mail: [email protected]
resinchronizing treatment was introduced. Optimization of
medicamental treatment with angiotensin converting enzyme (ACE) inhibitors and / or angiotensin receptor blockers, beta-blockers, aldosteron antagonists reduced morbidity and mortality due to HF. Nevertheless, in many patients
despite treatment HF is progressing. In the treatment of
worsening of systolic HF important role maintains digoxin
[1]. Digitalis glycosides which are among the most ancient
medications in treatment for cardiovascular diseases have
been firstly described by British doctor William Withering
in 18th century [2, 3]. Cardiac glycosides have positive
inotropic action, they improve contractile function, not
increasing heart rate. In cellular level digoxin is suppressing enzyme sodium-potassium adenosine triphophatase,
thus increasing intracellular level of calcium. Digoxin has
potential of neurohormonal suppression [2–4]. The first
big clinical trials RADIANCE (Randomized Assessment
of Digoxin and Inhibitors of Angiotensin Converting Enzyme) and PROVED (Prospective Randomized Study of
Ventricular Function and Efficacy of Digoxin) performed
in 1990 have proven big clinical benefit of digoxin use
in treatment of worsening of HF [4, 5]. DIG (Digitalis Investigation Group) trial has shown that digoxin improves
clinical symptoms and reduces hospitalization in patients
with systolic HF treated with ACE inhibitors and diuretics.
However, in patients treated with digoxin and in placebe
group mortality was similar, there was no influence on cardiovascular mortality [6, 7].
Use of digoxin in older patients
Thus, the aim of digitalis therapy is to improve quality of life, decreasing the symptoms and signs of heart
failure and to prevent hospitalization.
Heart failure is the most frequent cause of hospitalization among persons aged 65 years and above [2, 8].
Cardiac glycosides are widely used in older patients to
treat congestive HF and supraventricular tachyarrhythmias such as atrial fibrillation [9].
In the management of older patients it is important to
take into account age-related changes of pharmacokinetics and pharmacodynamics, decreased glomerular filtration rate, sex, and concomitant diseases [10]. Older individuals have lower tolerance of digitalis than younger
and the risk of digitalis toxicity is increasing with age
[2–4, 11]. Digitalis toxicity in 80% of cases is diagnosed
in patients aged 65 years and above [4]. Mortality from
acute digoxin intoxication in older age ranges from 8 to
58% [9]. In older age electrolyte imbalance and impaired
renal function is met more often. Although serum creatinine level is normal, glamerular filtration rate can be
decreased especially in patients with lower body mass
[12]. The most frequent causes predisposing to intoxication with digoxin are loss of potassium due to diuretics
or secondary hyperaldesteronism, older age, myocardial
infarction or ischemia, hypothyrosis, hypercalcemia, renal failure. Older patients often have several diseases,
they use many medications. Drugs increasing digoxin
toxicity are chinidin, eritromycin, verapamil, diltiazem,
captopril, anticholinergics, ibuprofen, amiodarone, clarithromycin [3].
Digoxin toxicity can be displayed with various symptoms and signs: head ache, nausea, vomiting, diarrhea,
changes in vision of colors, general malaise. More complex are arrhythmias caused by digoxin: sinus bradycardia, sinus pauses, atrioventricular blocks, ventricular
tachyarrhythmias [3–5, 8, 9]. Risk for digitalis caused
arrhythmias is increased by age, low potassium level,
chronic obstructive pulmonary disease (COPD), amyloidosis, worsening of kidney disease [4]. Digoxin can
cause pulmonary vasoconstriction in COPD patients.
These patients due to hypoxia and acidosis make high
risk group. Digoxin therapy should be avoided in treatment of right ventricular failure, caused by COPD [6].
Therapeutic digoxin levels usually vary; the lower
limit ranges from 0.6–1.3 ng/mL, while the upper limit
generally is agreed to be 2.6 ng/mL [3, 13]. Although assessment of serum digoxin level is not recommended as
obligatory routine test, serum concentration associated
121
with toxicity overlap between therapeutic and toxic ranges because of big number of factors potentiating digoxin
toxicity.
DIG clinical study has proven that in patients aged
65 yrs and older only small serum digoxin concentration (0.5–0.9 ng/mL) is related to reduce in all-cause
mortality. Older patients quite often have chronic atrial
fibrillation and heart failure. In these patients serum digoxin concentration 0.5–0.8 ng/mL is optimal [13, 14].
The recommended daily dose of digoxin for these patients is 0.125 mg per day [2, 11]. The treatment should
be started with the same dose. Even lower digoxin
dose, 0.125 mg every second day, is recommended for
the patients aged 75 and older, women, patients with
renal failure, treated with big doses of diuretics, with
repeated pulmonary oedemas [2]. Special attention
should be payed to women. They have increased risk
of digitalis toxicity. In older women digitalis toxicity
is met more often than in men [13, 15, 16]. Big digoxin doses increase lethality of older females [15, 17].
Digoxin concetration 0.5–0.8 ng/mL is associated with
decreased lethality in women as compared with placebo
group, thus recommended serum digoxin concentration
is below 1 ng/mL [13, 15].
To control heart rate in older patients with impaired
mobility digoxin monotherapy can be sufficient [12, 18].
However, many older adults live rather active life, are engaged in sports. In physical activity digoxin alone can not
ensure control of heart rate. In these cases, digoxin can
be used together with beta-blockers or calcium channel
blockers (verapamil, diltiazem) [12, 19]. Combination of
digoxin with beta-blockers is more effective and safe in
comparison with combination of digoxin with calcium
channel blockers [12]. Digoxin nowadays is not a drug
of choise to control heart rate in atrial fibrillation [7].
Digoxin in combination with carvedilol increases ejection fraction of left ventricle and decreases symptoms
of heart failure more effectively than both medications
separately.
Digoxin is decreasing morbidity but has no influence
on survival. Digoxin could be administered to all patients with heavy heart failure and decreased systolic
function together with ACE inhibitors, beta blockers,
spironolactone, diuretics. Thus, the role of digoxin in
treatment of heart failure remains secondary. In treatment of older patients it is important to set the optimal
dose, considering age, gender, renal function, concomitant diseases and medications used.
122
V. Lesauskaitė, T. Jankauskas
Conclusions
1. Aging is associated with increased digitalis toxicity.
2. For older patients recommended digoxin daily dose
is 0.125 mg and serum digoxin concentration of­
1 ng­/mL is sufficient.
3. For patients aged 75 years and older, women, having
renal failure, treated with big doses of diuretics recommended dose of digoxin is 0.125 mg each other
day.
4. To control heart rate in physically active patients
combination of digoxin with beta-blockers is recommended.
References
1. McDonagh TA. Challenges in advanced chronic
heart failure: drug therapy. Future Cardiology. 2008;
4(5): 517–25.
2. Ahmed A. An update on the role of digoxin in older
adults with chronic heart failure. Geriatr Aging. 2008;
11(1): 37–41.
3. Patel V, James PA. Digitalis toxicity. Available at:
www.medscape.com
4. Brownwald E, Zipes DP, Libby P. Heart Disease.
6th edn. W.B. Saunders Company. 2001: 573–5; 739.
5. Haji SA, Movahed A. Update on digoxin therapy
in congestive heart failure. Am Fam Phys. 2000; 62(2):
401–9.
6. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart
failure. N Engl J Med. 1997; 336: 525–33.
7. Rich MW, McSherry F, Williford WO. Effect of
age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG Study. J Am
Coll Cardiol. 2001; 38: 806–13.
8. Forman DE, Rich MW. Heart failure in the elderly.
Congestive Heart Failure. 2003; 9(6): 311–23.
9. Roever C, Ferrante J, Gonzalez EC, Pal N, Roetzheim RG. Comparing the toxicity of digoxin and digito-
xin in a geriatric population: should an old drug be rediscovered? Southern Med J. 2000; 93(2): 199–202.
10. Marx GM, Blake GM, Galani E, et al. Evaluation of the Cocroft-Gault, Jelliffe and Wright formulae in
estimating renal function in elderly cancer patients. Ann
Oncol. 2004;15: 291–5.
11. Aronow WS. Treatment of heart failure in older
persons. Available at: URL: http://www.medscape.com/
viewarticle/456940
12. Falk RH. Ventricular rate. Control in the elderly:
is digoxin enough? Am J Geriatr Cardiol. 2002; 11(6):
353–6.
13. 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(7): 871–8.
14. Weir RAP, Mcmurray JJV, Taylor J, Brady AJB.
Heart failure in older patients. Br J Cardiol. 2006; 13:
257–66.
15. Barclay L. Digoxin dose important in women with
heart failure. N Eng J Med. 2002; 347(18): 1394–7.
16. Rathore SS, Wang T, Krumholz HM. Sex-based
differences in the effect of digoxin for the treatment of
heart failure. N Engl J Med. 2002; 347(18): 1403–10.
17. Barclay L. Beware high serum digoxin concentrations. JAMA. 2003; 289: 871–8.
18. Watson T, Shanstila E, Lip GHY. Management of
atrial fibrillation: on overview of the NICE guidance on
AF management. Br J Cardiol. 2007; 14(1): 23–8.
19. Khand AU, Rankin AC, Martin W, Taylor J, Gemmell I, Cleland JGF. Carvedilol alone or in combination
with digoxin for the management of atrial fibrillation in
patients with heart failure? J Am Coll Cardiol. 2003; 42:
1944–51.
Received 15 May, 2010
Accepted 17 June, 2010
Use of digoxin in older patients
DIGOKSINO VARTOJIMAS VYRESNIO AMŽIAUS
PACIENTAMS
V. Lesauskaitė, T. Jankauskas
Kauno Medicinos Universiteto Geriatrijos Klinika
Santrauka
Progresuojančio sistolinio širdies neoakankamumo gydyme svarbią vietą tebeturi digoksinas. Gydant vyresnio amžiaus
pacientus, svarbu atsižvelgti į amžiaus įtakotą pakitusią vaistų farmakokinetiką ir farmakodinamiką, mažėjantį glomerulų filtracijos greitį, lytį ir gretutrines ligas. Vyresnio amžiaus
pacientai blogiau toleruoja digitalio preparatus nei jaunesni, o
toksinio poveikio rizika didėja su amžiumi. DIG (Digitalis In-
123
vestigation Group) klinikiniame tyrime išanalizavus 65 metų
ir vyresnius pacientus, nustatyta, kad tik esant mažai digoksino koncentracijai (0,5–0,9 ng/ml) mažėja bendras mirštamumas. Šiems pacientams rekomenduojama digoksino dozė yra
0,125 mg dienai. Digoksinas galėtų būti skiriamas visiems
pacientams, sergantiesiems sunkiu širdies nepakankamumu
ir sumažėjusia sistoline funkcija kartu su AKFI, beta-adrenoblokatoriais, spironolaktonu, diuretikais. Digoksino vaidmuo,
gydant širdies nepakankamumą, išlieka antrinis.
Raktažodžiai:
vyresnis amžius, digoksino toksiškumas, digoksino dozavimas