Preventable ADRs leading to hospitalization — results of a long-term prospective safety study with 6,427 ADR cases focusing on elderly patients

ABSTRACT

Background: Studies evaluating the impact of age and potentially inappropriate medication (PIM) on avoidable adverse drug reactions (ADRs) are scarce.

Methods: In this prospective, multi-center, long-term (8.5 years) observational study, we analysed ADRs leading to hospitalization in departments of internal medicine. ADRs causality and preventability were assessed using standardised algorithms. PIM was defined based on the PRISCUS-list. Multivariate analyses and estimation of ADR incidence rates were conducted.

Results: Of all 6,427 ADR patients, a preventable ADR was present in 1,253 (19.5%) patients (elderly patients ≥70 years: 828). Risk factors for preventable ADRs in elderly patients were multimorbidity, two to four ADR-causative drugs, and intake of particular compounds (e.g. spironolactone) but not sex, PIM usage, or the total number of drugs. Regarding particular compounds associated with preventable ADRs, highest incidence rates for preventable ADRs were found for patients aged ≥70 years for spironolactone (3.3 per 1,000 exposed persons (95% CI: 1.4–6.6)) and intermediate-acting insulin (3.3 per 1,000 exposed persons (95% CI: 1.6–6.1)).

Conclusion: Avoiding PIM usage seems to be of limited value in increasing safety in elderly patients whereas our results underline the importance of an individualized medication review of the most commonly implicated drugs in preventable ADRs (supported by BfArM FoNr: V-11337/68605/2008–2010).

KEYWORDS:

• Adverse drug event
• adverse drug reaction
• hospital admission
• elderly patients
• potentially inappropriate medication (PIM)
• preventability
• PRISCUS

Article highlights

• In a large, long-term observational study conducted in Germany, a higher proportion of preventable ADRs was found in elderly patients compared with younger patients.

• Whereas in younger patients non-consideration of contraindications, non-adherence, and self-medication were of relevance, non-consideration of e.g. comorbidities, and missing (non-drug-related) prevention and monitoring strategies were essential in elderly patients.

• PIM usage according to the German PRISCUS list was not associated with preventable ADRs leading to hospital admission in elderly patients.

Acknowledgments

SS and MR wrote the manuscript; PT and JH contributed substantially to the manuscript; all authors reviewed the manuscript. PT and JH designed the research project. Research was conducted by SS, MR, JS, BD, WS, MH, KF, IG, JH, PT. MR and SS analyzed and interpreted data with substantial contributions from PT and JH. The authors report no conflicts of interest. The authors are grateful for the help received from the following members of the Network of Regional Pharmacovigilance Centers: Dr. Karen Saljé, Kathleen Klein, Manuela Arnold, Kathleen Wergin (Greifswald); Dr. Silke Müller, Grit Haase, Anita Zachow, Dr. Susanne Nehls (Rostock); Dipl.-Pharm. Astrid Scheuerlein, Dorothea Gruca (Jena); Silke Surber, Dipl.-med. Kerstin Fricke, Beate Henzgen, Prof. Reinhard Fuenfstueck, Prof. Harald Schmechel (Weimar); Dr. Steffen Haffner (Wuppertal); Denise Kohn (Munich).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclosed.

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Funding

The Network of Regional Pharmacovigilance Centers received financial support from the Federal Institute for Drugs and Medical Devices from 1996 to June 2011 (project number V-11337/68605).