Better health care could be just a matter of time

New funding allows FoMD scientists to measure health outcomes of patients taking blood pressure medication at different times of the day.

Laura Vega - 09 September 2016

Timing matters in medicine-in fact, it matters so much it could make a significant difference on how effective a medication can be. Thanks to generous funding, the University of Alberta's Pragmatic Trials Collaborative will take on a new quality improvement project that will measure the outcomes of patients taking blood pressure medication, depending on the time of day they take their prescription.

Scott Garrison, associate professor with the Faculty of Medicine & Dentistry's Department of Family Medicine is the director of the group. He and his team recently received a Partnership for Research and Innovation in the Health System (PRIHS) grant, which is a joint funding initiative between Alberta Innovates-Health Solutions and Alberta Health Services to improve health outcomes for patients across Alberta.

"I'm very passionate about evidence-based medicine," says Garrison. "And I believe there are many trials of great importance to both patients and providers that are being overlooked. Subtle differences in how we prescribe medications might make big differences to our patients."

BedMed-the name of the blood pressure trials venture-will repeat a study conducted by another team in Spain in 2010, which suggested that taking blood pressure medication at bedtime instead of in the morning caused a 61 per cent reduction in death, heart attack and stroke. If these results are confirmed by the new trial, they could lead to a significant change in current therapeutics.

BedMed: Quality improvement for cardiovascular health

Garrison's team will work with more than 8,000 patients on the BedMed project. Through constant monitoring and recording events they will measure the difference of blood pressure medication's effects according to the time of day it is taken.

In addition to measuring the events related to blood pressure (hospitalization for stroke, heart attack or heart failure) the group wants to analyze other outcomes of interest. "We know older adults care about their independence, so that's always going to be an outcome in our trials: are you able to stay independent at home longer?" Garrison says.

There will also be an analysis of potential risks and safety, an aspect the past trials in Spain did not consider. Garrison explains: "For example, everybody's blood pressure is usually lower at night. If patients have their blood pressure dropped even further at bedtime, it's conceivable they could feel lightheaded and might fall more at night if they get up to go to the bathroom."

The funding received allows the pragmatic trials group to begin this study in Alberta but the plan is to eventually obtain additional funds and expand the trials to other provinces like British Columbia and Manitoba, where the project has drawn the interest of many family physicians as well. More than 400 physicians have expressed their interest to participate with the Pragmatic Trials Collaborative in this trial, most of them in Alberta.

Getting patients INRange

Garrison's BedMed project follows closely after another project called INRange, a similar analysis on timing and effects of warfarin-a widely-used anticoagulant.

INRange (a reference to the international normalized ratio or INR, the test used to measure the effects of warfarin) was the group's first project designed to study the difference in the effects of the anticoagulant depending on the time it is taken, as opposed to the common practice of ingesting it with dinner.

According to Garrison, most people take warfarin in the evening. The potential issue is its interaction with vitamin K, a nutrient that is essential for the production of blood-clotting proteins in the body. Vitamin K is found in green leafy vegetables-most commonly eaten at dinner or lunchtime-and typically dissipates in the body over the course of several hours.

"Warfarin stops the activation of vitamin K and reduces the number of clotting factors as a result," says Garrison. "Most patients currently take warfarin at the same time as the most highly variable consumption of vitamin K. If they took warfarin in the morning-because breakfast foods usually don't have vitamin K-you would have a consistently low vitamin K effect while the warfarin effect might be the greatest. That might produce a more stable anticoagulant effect."

"This is all speculative but nobody has ever looked to see if the time of day warfarin is taken actually matters."

With this theory in mind Garrison's group gathered 236 family physicians who agreed to participate in the study, a very impressive number above most precedents for participation of family doctors in independent trials. The INRange trial is currently completing its follow-up and expects results to be available in the fall.

Answers for family physicians with their own daily data

Garrison became familiar with administrative data (information naturally produced by primary care practices about their patients' diagnoses, for billing purposes) while working on his PhD in British Columbia, and realized it was possible to design trials in which family doctors could participate without disrupting their practice: studying common situations as they treat their patients and answering questions that could change their usual procedures and prescriptions. Pragmatic Trials Collaborative

He began to brainstorm different ideas for trials in 2012. Then he was contacted by U of A's Lee Green, chair of the Department of Family Medicine and Mike Allan, director of Evidence Based Medicine, who asked him to bring these initiatives to Alberta. The three of them, along with associate professors Michael Kolber and Christina Korownyk, became the core team of the Pragmatic Trials Collaborative.

The group has several funding and collaboration partnerships including EnACt (supported by Lee Green as AIHS Translational Health Chair in Engaged Scholarship), the SPOR data platform for data analysis, the Health Quality Council of Alberta, the Alberta College of Family Physicians and the initial funding received in BC by the Richmond Hospital Foundation. The new grant will take their work even further.

"The PRIHS grant is not only about the trial, but about how we then change behaviour province-wide if we learn something new and important. With so many family physicians engaged, we have a whole suite of innovative approaches to lead change once we define the best way to go."

Meet our funding partners

Alberta Innovates-Health Solutions (AIHS) is a public entity that delivers funding and support to a broad array of health research and innovation activities throughout Alberta. Their vision is to transform the health, health system and well-being of Albertans through research and innovation.

Alberta Health Services (AHS) is Canada's first and largest province-wide integrated health system, whose programs and services are offered at more than 650 facilities. AHS also provides facilities and community locations for clinical education of students from Alberta universities and colleges.