Ontario study identifies potentially harmful drug combinations prescribed to older adults

The research, published in BMJ and led by Dr. Paula Rochon, Director of Research at the Weston and O’Born Centre for Mature Women’s Health at Sinai Health, has revealed that certain drug combinations are a common but unrecognized contributor to drug related harm at the population level and add unnecessary costs to the healthcare system.

A potentially inappropriate prescribing cascade (PIPC) happens when a medication’s side effect gets mistaken for a new health problem, leading to another prescription that may not have been needed in the first place. One common example flagged in the study involves non-steroidal anti-inflammatory drugs (NSAIDs). Commonly prescribed for pain, these drugs are associated with a rise in blood pressure, which can lead to a new prescription for high blood pressure, rather than a second look at the original pain medication. Older adults are especially vulnerable to this pattern because they're more likely to be on multiple medications at once, due to having multiple conditions, making it harder for both patients and clinicians to trace a new symptom back to an existing drug.

"These sequences of events are common but often missed in clinical practice," said Dr. Rochon, who holds the Barry J. Goldlist Chair in Aging and Health at Sinai Health and is also a professor of medicine at the University of Toronto. "Knowing what medications, you are taking, when they were started and for what indication is important in order to identify possible prescribing cascades that may be problematic "

The study brought together an interdisciplinary, international team of collaborators and leaders in drug prescribing and geriatric medicine research from the United States, Belgium, Italy, Israel and Ireland, along with Sinai Health researchers Drs. Vasily Giannakeas, Nathan Stall and Christina Reppas-Rindlisbacher and research staff Wei Wu and Joyce Li.

With the expertise of 12 international panelists specializing in internal medicine, geriatric medicine and clinical pharmacology, the research team previously created a list of 65 PIPCs. Using this list and population-level prescription data from ICES, Ontario’s health data institute working with Lavina Matai and Zhiyin Li, the researchers examined each PIPC against three factors: how common the initial drug was in the population, how often it was followed by the second drug, and how strong the link was between the two. That analysis allowed them to pinpoint the 24 potentially inappropriate prescribing cascades most commonly seen in the population and with a potential to cause harm.

Seeing the pattern behind every prescription

For Dr. Rochon, the findings highlight a gap that opens quietly, one prescription at a time. “Our concern is that so often these conversations between the health care prescriber and the patient are being missed, so people don’t recognize the sequences of events and that they are connected to one another,” she said.

Closing that gap means physicians need to think about medication history at every visit, not just what a patient is currently taking, but why each drug was started in the first place, and whether the next one was really needed. 

The work also carries a particular weight for mature women, as they tend to live with more chronic conditions than men over their lifetime. Mature women are prescribed more drug therapies, and experience more adverse drug events. By being on multiple medications at once, they are more exposed to the risk that a drug's side effect gets mistaken for a new diagnosis rather than traced back to its source.

The team’s findings point to promising next steps. 

The first involves technology. Automated clinical decision support tools could flag a prescribing cascade in real time and prompt a second look before a new prescription is added. This information could be leveraged in one of several automated ways to help clinicians be aware of these potentially inappropriate prescribing cascades at the point of care.  

Next is optimizing the role of pharmacists as part of the care team and more directly integrating them into the prescribing process alongside physicians. Their expertise can help identify these potentially inappropriate prescribing cascades for further evaluation.

This research was funded by the Canadian Institutes of Health Research (CIHR) and supported by ICES.