Preventable and Non-Preventable Risk Factors for Adverse Drug Events Related to Hospital Admission in the Elderly

J. Doucet, A. Jego, D. Noel, C.E. Geffroy, C. Capet, A. Coquard, E. Couffin, A.L. Fauchais, P. Chassagne, D. Mouton-Schleifer and E. Bercoff


Clin Drug Invest. 2002;22(6) 

In This Article


Initially 2814 patients were consecutively included in the study, but patients were excluded when information about treatment was insufficient (77 patients) or when the analyses of the two investigators were conflicting (46 patients). 2691 patients (mean age 82.4 ± 7.8 years) were included in the final study.

Five hundred ADEs were considered 'probable' and concerned 429 inpatients (84.3 ± 6.5 years old; men 18.6%, women 81.4%). The mean duration of hospitalisation was 14.1 ± 11.3 days. The mean number of drugs was 7 ± 3 drugs per patient. The mean creatinine clearance, assessed by Cockroft's formula, was 47.5 ± 13.6 ml/min. Creatinine clearance was between 30 and 60 ml/min in 54.9% of patients and was less than 30 ml/min in 21.2%.

Of the 500 ADEs, 346 (69.2%) involved cardiovascular, metabolic, renal or neuropsychological symptoms ( Table I ). 41.8% of the ADEs were severe and 11 patients died: four because of haemorrhagic signs with an anticoagulant drug (heparin 2, acenocoumarol 2), one from dehydration (furosemide), two from renal failure (bumetanide + captopril, enalapril + diclofenac), three from aspiration pneumonia (haloperidol + bromazepam, flunitrazepam, prazepam + clomipramine) and one from cardiogenic shock linked to an antiarrhythmic drug (cibenzoline). Other ADEs (58.2%) were moderate. The outcome was favourable in 97.2% of the ADEs.

The 500 ADEs were caused by 1034 drugs, either alone or in combination. The drugs were mainly cardiovascular (43.7%) and psychotropic (31.1%) agents ( Table II ).

Drugs or drug combinations responsible for the ADEs had been administered for 1 month or more in 276 ADEs (55.3%), and for less than 1 month in 224 ADEs (44.7%). 91.6% of the drugs involved in an ADE were discontinued as soon as the ADE was diagnosed. The dosage was only decreased in 9.4% of the other drugs.

One or more risk factors were recorded in 406 of the 500 ADEs(81.2%). These were mainly DDIs and/or interfering acute diseases ( Table III ). DDIs were the most frequent risk factors; one DDI was involved in 303 of the 500 ADEs (60.6%).

An interfering acute disease (mainly acute dehydration) was involved in 221 ADEs (44.2%). This was significantly more frequent in ADEs resulting from drugs or drug combinations administered for 1 month or more (152 of 276 vs 69 of 124, respectively, p < 0.05).

Drug doses were excessive in 14.8% of ADEs. Eleven percent of ADEs were a result of one or more interfering chronic diseases that had not been taken into account by the physician at the time of prescription. Chronic renal failure was the main associated chronic disease (about two-thirds of chronic diseases).

Finally, 653 risk factors (isolated or associated) were recorded in 406 of the 500 ADEs; two or more risk factors were associated with 216 of the 500 ADEs ( Table IV ).

Among the 653 risk factors, 270 (41.3%) were preventable (some DDIs, excess doses and interfering chronic diseases) and 383 were nonpreventable (other DDIs and interfering acute diseases) [ Table III ]. One hundred and forty-one of 303 drug combinations were inappropriate (46.5%), resulting in DDIs. The other DDIs involved in ADEs were adapted to the clinical context and were considered non-preventable.

In many situations there was a combination of several risk factors. Some of these were preventable and others were non-preventable for the same ADEs. One risk factor alone or the combination of all risk factors was considered to be preventable in 201 of the 500 ADEs (40.2%), which represented 49.5% of the ADEs due to one or more risk factors ( Table IV ).