The Association of Potentially Inappropriate Medication at Older Age With Cardiovascular Events and Overall Mortality: A Systematic Review and Meta-Analysis of Cohort Studies

Abstract

Objective: The aim of this systematic review was to identify, evaluate, and meta-analyze cohort studies reporting the association of potentially inappropriate medication (PIM) intake with mortality and cardiovascular events.

Design: A systematic review and meta-analysis of prospective and retrospective cohort studies were conducted. Study appraisal included a thorough risk of bias assessment. Data synthesis followed a random-effects model.

Data sources: The included studies were retrieved from the databases MEDLINE and ISI Web of Knowledge. Additionally, the authors checked the references of the included studies for further relevant literature.

Eligibility criteria for selecting studies: For inclusion in a study, the population needed to be older than 60 years of age and not restricted to having one specific disease. The outcome had to address all-cause mortality or cardiovascular events. Studies that examined polypharmacy or specific drugs were excluded.

Results: At first, 13 studies were included in a meta-analysis. The association of PIM with overall mortality was not statistically significant (risk ratio; 95% confidence interval, 1.13; 0.95-1.35). However, the majority of studies showed a high risk of specific forms of bias. These biases can be excluded by applying a new user design. It ascertains that adverse events occurring early in therapy are recorded. After restricting the meta-analysis to three studies with a new user design, the association of PIM use and mortality was statistically significant (risk ratio; 95% confidence interval, 1.59; 1.45-1.75). Only one study focused on cardiovascular events and found no statistically significant association. However, the study was not conducted with a new user design.

Conclusion: In studies with adequate methods (new user design), PIM use, defined by Beers criteria or the HEDIS-DAE list, was associated with a 1.6-fold increased mortality in older adults. Physicians should therefore avoid prescribing PIM for older adults whenever feasible. Further new user design studies are required for cardiovascular outcomes and to compare the predictive value of different PIM criteria for mortality.

Keywords: Potentially inappropriate medication; medication problems; meta-analysis; older adults; potentially inappropriate prescribing; systematic review.