J CUn Epidcmiol Vol. 46, No. II, pp. 13OS1314, 1993 Printed in Great Britain. All rights reserved 089574356/93 $6.00 + 0.00 Copyright 0 1993 Pergamon Press Ltd THE IMPACT OF AGE ON RISK OF ADVERSE DRUG REACTIONS TO DIGOXIN MARCOPAHOR,‘*~JACK M. GURALNIK,~ GIOVANNI GAMBASSI,~ ROBERTO BERNABEI,’ LUCIANA CAROSELLA’ and PIERUGO CARBONIN,’ for the GRUPPO ITALIANO DI FARMACOMGILANZA NELL’ANZIANO ‘Cattedra di Gerontologia, Universita’ Cattolica de1 Sacro Cuore, Rome, Italy, *Epidemiology, Demography and Biometry Program, National Institute on Aging, Bethesda, MD 20892 and ‘Gerontology Research Center, National Institute on Aging, Baltimore, MD, U.S.A. zyxwvutsrqponmlkjihg (Received in revised form 14 June 1993) Abstract-To assess the association of age and other potential risk factors with digoxin toxicity, adverse drug reactions to digoxin (ADRDIG) were studied in all patients (n = 1338) on digoxin therapy consecutively admitted to 41 clinical wards throughout Italy during 4 months in 1988. At the time of admission, 28 patients (2.1%) had evidence of ADRDIG. In multivariate logistic regression analysis, significant associations with ADRDIG were found for age > 80 years compared to age 65-79 years (OR = 2.75,95% CI = 1.17-6.45), daily digoxin dosage of 30.25 mg (OR = 2.51, 95% CI = 1.16-5.47), serum creatinine > 120 pmol/L (OR = 3.75, 95% CI = 1.69-8.32), and for treatment with amiodarone, propafenone, quinidine or verapamil (OR = 2.60, 95% CI = 1.07- 6.30). Those aged < 65 years had a similar risk of digoxin toxicity as those aged 65-79 years (OR = 1.07, 95% CI = 0.284.12). Adverse drug reactions to digoxin were found in 1 in 50 patients hospitalized on digoxin therapy. Patients aged 65-79 years were not at increased risk for digoxin toxicity compared to younger patients, while advanced age (2 80 years) was an independent risk factor for this outcome. Digoxin Adverse drug reactions Elderly Hospital admission Pharma- coepidemiology Multivariate analysis INTRODUCTION Digoxin in one of the most frequently pre- scribed drugs in the community [l] and in hospital settings [2]. The elderly population is more likely to be on digoxin therapy because of the increased prevalence of heart failure and atria1 fibrillation with increasing age. In clinical practice it is commonly believed the digoxin toxicity is more frequent in the older population [3]. The drug has a very narrow therapeutic index and there is a higher risk of toxicity in those who suffer from multiple diseases, con- *All correspondence should be addressed to: Marco Pahor, M.D., Cattedra di Gerontologia, Universita’ Cattolica de1 Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy. tThis work was partially completed when Dr Pahor was a visiting scientist at the U.S. National Institute on Aging. sume multiple drugs and have impaired renal function [4]. In addition to altered pharmacoki- netics leading to higher serum levels, the elderly may be more sensitive to digoxin. Toxic mani- festations have been frequently found with normal serum digoxin levels [5-91. Despite the conventional wisdom that digoxin toxicity increases with age, only 2 of 9 pharma- cosurveillance studies on digoxin found a stat- istically significant correlation between age and adverse drug reactions to digoxin (ADRDIG) [ 10, 111. In the remaining studies there was no significant difference in mean age in those with and without ADRDIG although most showed a trend towards higher age in the toxic group [5,6, 12-161. These inconsistent results may be explained by the low proportion of very old 1305