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Multi-regional data supports the largest randomized trial ever conducted by Canadian primary care

Dr. Scott Garrison, a smiling white man with short brown hair. The Health Data Research Network logo is at bottom.
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Can blood pressure medication taken at bedtime rather than breakfast significantly reduce the risk of cardiovascular events? After reading research from Spain with promising findings, Dr. Scott Garrison wanted to know more. “If the timing of medication was proven to have an impact on health outcomes, it could be hugely beneficial since it’s such a small, low cost change to make.”

Dr. Garrison, a family physician with a PhD in Experimental Medicine, turned to HDRN Canada’s Data Access Support Hub (DASH) to launch the largest pragmatic randomized trial ever conducted by Canadian primary care. DASH is a one-stop data access service portal for researchers requiring health administrative data from more than one province or territory in Canada. Dr. Garrison’s multi-regional study used data from five provinces to examine whether the timing of blood-pressure medication has any impact on health outcomes. 

“The main thrust of what we’re doing is trying to incorporate pragmatic trials of fairly simple interventions into daily care. Medication timing is an easy one to start with as it isn’t challenging for physicians or patients to implement,” explained Dr. Garrison, who is also the founder of the Pragmatic Trials Collaborative, a group of practicing primary care providers from across Canada that conducts large community-based pragmatic trials. Pragmatic trials are a type of clinical research that aims to assess the effectiveness of specific medical interventions in a real-world setting, making use of routinely-collected data to produce results that translate into improved health care policies and practice.

Dr. Garrison’s BedMed study recruited 3357 participants through 436 primary care providers based in British Columbia, Alberta, Saskatchewan, Manitoba and Ontario. Potential participants were identified using electronic medical records at primary care clinics. The research team then provided each clinic with recruitment packages and consenting participants were allocated using central randomization to either a bedtime or morning use of their medication. Participants also consented to administrative health data being accessed and analysed to support the trial and determine outcomes such as mortality, hospitalization, stroke, hip fractures or nursing home admission. 

“High blood pressure while you sleep is a bigger risk than high blood pressure during the day, so there was good cause to examine the impacts that medication timing might have on heart attack and stroke, as well as other health effects like risk of falling, visual problems due to glaucoma or vascular dementia – all of which relate to blood pressure,” said Dr. Garrison. “With this pragmatic trial, we were able to look at falls and fractures, cognition problems and vision, on top of cardiovascular events, and conclude that there was no difference with medication timing.” While the study ultimately found no difference in outcomes based on the timing of when medication was taken, the process of conducting the pragmatic trial “answered an important question about medication timing that will inform how primary care providers advise their patients in the future,” he added.  

Data stewards at five HDRN Canada member organizations played a key role in the pragmatic trial’s success, particularly with the consent process, Dr. Garrison said, adding that using multi-regional data from five Canadian provinces allowed for more participants and produced more generalizable results. Accessing the data through HDRN Canada’s DASH service facilitated a streamlined and coordinated experience across multiple data centres.

Dr. Garrison presented the results of the BedMed study at the European Society of Cardiology 2024 Congress. “There were around a thousand cardiologists in the audience and I could see that it was an important study to them because there was concern about how reliable the prior evidence was in this area, and about whether they should be changing the timing of these drugs.” The BedMed study is currently under review with JAMA.

Next steps for the research team included using the same data sets to publish a paper on the differences in health behaviours between people who volunteer for randomized trials and those who don’t. “Because we are working with administrative data, we are in a unique position where we can examine the health behaviours and outcomes of people who volunteer for trials like BedMed, and compare them to those who were invited but don’t volunteer. We already know volunteers are different, but this work can tell us how different they are when it comes to screening and preventive measures,” Dr. Garrison said.

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