Discussion

This post-hoc analysis of a randomised controlled trial (MedBridge) in older patients identified multiple risk factors and protecting factors for drug-related readmissions within 12 months after hospital discharge. Sixteen risk factors related to age, previous hospital visits, medication use, multimorbidity and cardiovascular, liver, lung and peptic ulcer disease were identified. Protecting factors for drug-related readmissions were previous dementia diagnosis, and urinary tract infection and injuries, intoxications and other complications of external factors as discharge diagnosis. Sixteen percent of the hospital revisits assessed in this study were potentially preventable drug-related revisits. The two most prevalent diseases and causes related to preventable revisits were heart failure and COPD, and inadequate treatment and insufficient or no follow-up, respectively.
The identified risk factors in this study confirm results of previous studies showing that age, previous hospital visits, number of medications and comorbidity were positively associated with drug-related readmissions [1,3]. Although there is little agreement on specific diseases that affect drug-related visits in the literature, cardiovascular disease and its treatment are often reported as risk factors for drug-related (re)admissions [1,3,4]. Previous liver disease and peptic ulcer disease were the risk factors with the highest HRs, but are not commonly identified risk factors in other studies. Pharmacotherapy for management of severe liver disease and adjustment of pharmacotherapy based on changes in pharmacokinetics and pharmacodynamics due to liver disease are challenging for clinicians [16,17]. Hence, it seems plausible that inappropriate pharmacotherapy for patients with existing liver disease may cause hospital admissions. A previous study by our research group at Uppsala University Hospital, one of the current study sites, found that medications prescribed for peptic ulcer or gastroesophageal reflux disease were associated with an increased risk of readmission in older patients [18]. Furthermore, medications that may cause gastroduodenal bleeding (e.g., antiplatelets and anticoagulants) are often identified as risk factors for drug-related readmissions [1,3] and this risk may be higher in patients with previous peptic ulcer disease. However, our results on previous liver and peptic ulcer disease should be interpreted with caution, as the prevalence rates of these diseases in medical histories were low (n=16, 0.6%, and n=37, 1.4%, respectively) and no related revisits of patients with these diseases were identified in our random sample of 400 participants. Lung disease (mainly COPD) in the medical history and as discharge diagnosis were risk factors in our study, confirming the results of our previous study at Uppsala University Hospital showing that asthma and COPD were associated with an increased risk of readmission [18]. Interestingly, previous dementia diagnosis was a protecting factor for drug-related readmissions in our study, in contrast to other studies that have identified cognitive impairment or dementia as risk factors for drug-related (re)admissions [19,20]. A possible explanation may be that dementia generally occurs in more complex patients and that their readmissions may frequently be classified as ‘caused by progression of the disease’ (i.e., unlikely to be drug-related), rather than being caused by a DRP. This is supported by dementia not appearing as a protecting factor for all-cause readmission in our secondary analysis. The other protecting factors in our study (urinary tract infections and injuries, intoxications and other external factors as discharge diagnosis) may be explained by their relative unrelatedness to pharmacotherapy, in contrast to other discharge diagnoses.
The prevalence of potentially preventable drug-related revisits in our study (47% of all possibly drug-related visits and 16% of all unplanned visits) confirms the average prevalence in recent systematic reviews (43% of drug-related readmissions based on six studies [4] and 15% of all-cause readmissions based on four studies [3]). The diseases most often related to these preventable visits were cardiovascular disease (mainly heart failure, 28%) and COPD (13%), followed by gastrointestinal bleeding or ulcer (8.2%). These results seem in line with the identified risk factors for drug-related readmissions in this study. For both heart failure and COPD, inadequate use of medications is associated with poor clinical outcomes and exacerbations are often avoidable through better prescribing by clinicians and clearer instructions for patients [21–24]. Gastroprotective proton pump inhibitor treatment is an evidence-based strategy to prevent gastrointestinal bleeding or ulcers. However, recent Swedish studies focusing on the potential harmful effects of long-term proton pump inhibitor treatment may have led to the restrictive use of gastroprotection in older patients [25–27].
The three main causes (inadequate treatment, insufficient or no follow-up and non-compliance) that accounted for 78% of all preventable revisits in our study indicate the potential for improvement through better treatment guideline adherence and patient involvement and education [28,29]. Further, 39% of the potentially preventable drug-related revisits could have been prevented by the medication review in the MedBridge trial, if the review had been performed optimally. A previous process evaluation of the trial found a lack of integration of medication reviews into the daily workflow at the ward, inadequate time allotted for follow-up on treatment changes and no medication reconciliation upon discharge by the pharmacist in more than half of the patients [30]. Improving these shortcomings could make medication review an effective strategy to prevent hospital revisits. However, our results indicated that an estimated 6% reduction in hospital revisits within 12 months (39% of the 16% potentially preventable drug-related revisits) might be the maximum achievable by a hospital-based pharmacotherapy intervention, making it challenging to conduct adequately powered clinical trials.
This study has several strengths. The large study population with long and complete post-discharge follow-up and the use of a validated method to identify drug-related revisits increase the reliability of the results. There are also some limitations to the study. Only patients who had been admitted to general internal medicine or internal medicine subspecialty wards were included, which limits generalisability to a broader group. We excluded one-day admissions, patients who had recently undergone a medication review and patients receiving palliative treatment, which may have led to the exclusion of patients with both relatively mild and severe health conditions. All analyses and assessments were based solely on electronic data from the regional health registries and the hospitals’ general EHR systems, which could lead to potential under- or overestimation of study outcomes. Cytostatic treatment is often prescribed in a separate system that was not accessible to the researchers. Hence, cancer was a risk factor for all-cause readmissions in our study, but not drug-related readmissions. Anticancer drugs have been associated with readmissions in previous studies [1,3]. For risk factor analysis, we lacked data about medications upon discharge, although we included the number of medications upon admission. For the preventability assessment, we chose not to include which medications were involved in each drug-related visit, because of the generally complex pharmacotherapy and multiple medications involved (e.g., inadequate heart failure treatment often involves (the lack of) four different drug substances). We could have reported all therapeutic drug classes that were potentially involved, but the reliability of such results would have been questionable.

Conclusion

Risk factors for drug-related readmissions in older hospitalised patients were age, previous hospital visits, multimorbidity, medication use and cardiovascular, liver, lung and peptic ulcer disease. Potentially preventable drug-related hospital revisits are common and might be prevented through adequate medication use and follow-up in older patients with cardiovascular or lung disease. Interventions to reduce drug-related hospital visits are generally conducted in older patients with multiple medications in use. In addition, the study suggests focusing on patients with multiple previous visits and those with heart failure or COPD. Hospital revisits in these patients may be prevented through better treatment guideline adherence concerning adequate pharmacotherapy and treatment follow-up, and through better patient education and involvement.