Adverse drug events after hospitalization: Are we missing the mark?

Care transitions, from an acute care hospitalization to home, are an especially dangerous time for older adults and can affect patient outcomes, cause harm, and when done poorly, be extremely costly.^1,2 Patients receive medications from new and different providers which can lead to errors or discrepancies,³ including inappropriate discontinuation or unintentional inclusion of medications.⁴ Even if not prescribed in error, new medications have the potential to cause an adverse event. At least 20% of older adults will experience an adverse event in the weeks following hospitalization, with the majority being secondary to adverse drug-related events (ADEs). Of these, half are considered preventable or ameliorable.⁵

In this issue of JAMA Internal Medicine, Gurwitz,⁶ et al report results of a pharmacist-led intervention targeting high risk older adults in an attempt to improve medication safety during the transition of care from hospital to home. The authors focused specifically on patients prescribed one or more medications already known to be high-risk, specifically anticoagulants, diabetes agents and opioids. The intervention comprised home visits within 4 days of discharge including an in-home assessment of medication by a clinical pharmacist, printed educational resources, a follow-up telephone call 14 days later and communication with the patients’ primary care team. After 45 days of follow-up, 28% of participants experienced at least one adverse drug-related incident (i.e., an actual or potential ADE) with the most common causal medication being opioids. Despite the intensive intervention, the authors found no difference in the rate of adverse drug-related incidents or more specifically “clinically important medication errors” between the intervention and control groups. This latter outcome is especially noteworthy: while some adverse events will be unavoidable, the clinically important medication errors encompass those amenable to intervention, as a combination of preventable ADEs (ADEs due to errors in prescribing, dispensing, or use), ameliorable ADEs (ADEs which can be caught and mitigated early), and potential ADEs (medication errors which have potential to cause harm but have not yet done so). Notably, 58% of the ADEs in this study fell into these categories, suggesting that had the intervention been successful, a large number of ADEs might have been mitigated.

There are many features of this intervention that increased the likelihood it would be successful. First, pharmacist interventions have been shown to be among the most effective strategies to combat ADEs since pharmacists are uniquely suited for this role as medication experts, have expertise in addressing medication related problems and more deeply understand patients’ perspectives and actual use of medications in real life. Second, this study included communication with the primary care team via the electronic health record at both the home visit and for any urgent medication-related problems. This was a critical addition as lack of communication with primary care is a criticism of many prior pharmacist-led studies.

However, the study faced some pitfalls as well. Despite the large number of eligible participants, ultimate recruitment numbers were quite low. In fact, the eligibility criteria had to be expanded from patients aged ≥ 65 years old to include patients aged 50-65 years old in order to boost recruitment. Even with this broader inclusion criteria, the original goal of 500 participants was not met. This left the study underpowered: the finding that the intervention reduced clinically important medication errors by 19% - although not statistically significant and thus unconfirmed – would be a clinically meaningful improvement if true. In addition, it is likely that some ADEs occurred prior to the first home visit making this intervention poorly suited to prevent ADEs occurring immediately after discharge. At best, the intervention could identify and aid in fixing these early ADEs but would not prevent them.

While a number of attempts have been made to improve prescribing quality and reduce post-hospital ADEs by accompanying patients through their care transition, many have had disappointing results. We now have this pharmacist-led, thoughtful, human facing, intensive, primary care connected intervention that did not find a difference between the two groups of patients on high-risk medications, and in fact struggled simply to recruit enough patients to participate.⁶ Something isn’t working.

It is time to take the next leap forward. While careful and coordinated post-discharge follow-up should undoubtedly continue, we need to more carefully consider the medications we are prescribing, especially at hospital discharge. The best way to prevent ADEs is to not prescribe a drug that isn’t truly necessary in the first place. Therefore, we should first focus on limiting non-essential medication changes or additions in the hospital setting. Does the patient really need a prescription for opioids, or could the acetaminophen that they are already using be as effective? Is a new anti-hypertensive essential? These changes will aid the robust work focused on deprescribing medication once the patient has transitioned home.

Moreover, as a healthcare system we need to find a way to engage patients and caregivers in this work. The recruitment challenge this study faced may in fact be signaling a larger issue, that patient engagement is central to creating change. Patients may feel disempowered and so disengage from being an active participant in their medical care, especially with regards to medication use. This would pose a problem to any potential intervention, no matter how well-designed.⁷ Perhaps this study had a negative result not because pharmacists aren’t integral to medication planning, but because they need to be part of a larger system of care that centers the patient and caregiver in the process, empowering them to be active participants in medication prescribing and use. Medication reconciliation at admission and discharge has been another focus of study to improve prescribing safety at discharge, but this does not engage patients or their caregivers in identifying problems or activating patients to raise concerns or questions during this critical care transition. Helping patients and caregivers feel engaged with medications choices, effectively communicate, and know what to communicate, will be essential.

As this study illustrates, preventing adverse drug-related events is hard. Many attempted interventions have negative findings as this one does, or only incremental gains with costly, challenging and complex interventions, leaving many in the medical community to worry that we are still far from the right answer. Perhaps then, our focus should fall more heavily not just on “swooping in” to rectify adverse drug-related events after hospitalization, but rather decreasing non-essential medication prescribing and changes during the transition out of the hospital and engaging patients and their caregivers throughout. Solving the problem will require attention to judicious discharge prescribing and also systems-level changes that involve a team of providers and empower both patients and caregivers to be at the center of and direct their care.