Polypharmacy and adverse drug reactions in Japanese elderly taking antihypertensives: a retrospective database study

Background: The concomitant use of multiple medications by elderly patients with hypertension is a relatively common and growing phenomenon in Japan. This has been attributed to several factors, including treatment guidelines recommending prescription of multiple medications and a continuing increase in the elderly population with multiple comorbidities. Objective: This study was aimed at investigating the association between polypharmacy, defined as the concomitant use of five or more medications, and risk of adverse drug reaction (ADR) in elderly Japanese hypertensive patients to examine the hypothesis that risk of ADR increases with the administration of an increasing number of co-medications. Methods: Using a retrospective cohort design, the data regarding all hypertensive patients aged 65 years or older were extracted from the Risk/Benefit Assessment of Drugs - Analysis and Response Council antihypertensive medication database. The data were reviewed for classification of patients into one of three groups according to drug use at the initiation of therapy - a monotherapy group composed of patients who had taken the investigated drug only, a comedication group composed of patients who had taken the investigated drug and a maximum of three other medications, and a polypharmacy group composed of patients who had taken the investigated drug and four or more other medications - and determination of the number of ADR events experienced. Estimated rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using a Poisson regression model adjusted for drug category and patient age and sex. Various sensitivity analyses were performed to confirm the robustness of the study findings. Results: Of 61,661 elderly Japanese patients (men, 41.8%; 75 years or older, 35.1%) registered in the database, 2491 patients (4.0%) experienced a total of 3144 ADR events during the study period. The rate of ADR per 10,000 person-days was 2.0 for the monotherapy group, 5.1 for the co-medication group, and 8.6 for the polypharmacy group. After adjusting for age, sex, and initial antihypertensive therapy, the RR was estimated at 2.4 (95% CI, 2.2-2.6) for the co-medication group and 4.3 (95% CI, 3.8-4.8) for the polypharmacy group, when compared with the monotherapy group. Conclusion: The use of polypharmacy increases the risk of ADR among elderly Japanese patients with hypertension, calling for regular medication review to eliminate the administration of unnecessary co-medications.