Maura Marcucci (MD), assistant professor in the Department of Health Research Methods, Evidence and Impact at McMaster University, and James Douketis (MD), an expert in thromboembolism, discuss blood pressure control strategies in patients undergoing to non-cardiac surgeries, according to the recent POISE-3 trial.
To read an article discussing the findings of the POISE-3 trial on hypotensive pharmacotherapy before and after surgery, click here.
James Douketis (MD): Hello everyone. My name is Jim Douketis and it is my pleasure to welcome you to another episode of [McMaster Perspective]. The series is part of the manual [McMaster Textbook of Internal Medicine]. Every few weeks we invite an individual associated with an important publication with the potential to change practice.
This time I have the pleasure of introducing you to Dr. Maura Marcucci, who is an associate professor in the Department of Medicine at McMaster University and a scientist at the Population Health Research Institute. Maura led the POISE-3 (PeriOperative Ischemic Evaluation 3) study, which investigated perioperative blood pressure control strategies for non-cardiac surgeries.
Welcome, Maura. It’s a pleasure to have you here to hear about your important work.
Maura Marcucci (MD, MSc): Thank you very much, Jim. Thank you very much for inviting me.
James Douketis: The POISE-3 study investigated the titration of hypotensive agents, particularly angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor antagonists (ARBs), in the perioperative period in patients undergoing non-cardiac surgeries.
Maura, perhaps we can start with your impression about the standard of care before the POISE-3 study, in terms of perioperative discontinuation or continuation of ACEIs and ARBs.
Maura Marcucci: Thank you very much, Jim. We have some data from the VISION (Vascular Events in Noncardiac Surgery Cohort Evaluation) cohort study to answer your questions.
In summary, the VISION cohort study was a large international observational study, involving patients undergoing non-cardiac surgery, it is a global study. These data demonstrate that in more than 70% of the patients included in the study, the administration of hypotensive agents, including ACEIs and ARBs, was not interrupted in the 24 hours before surgery.
This was in 2014-2015. At the beginning of POISE-3, most likely, the practice had really changed. So we used preliminary evidence that possibly discontinuing ACEIs or ARBs could reduce perioperative hypotension and potentially limit cardiovascular complications.
I would say that when we started POISE-3, the proportion of patients who in the perioperative period were still receiving their usual treatment with ACEIs or ARBs was most likely less than 70%, but I would say that there was still uncertainty. There was still much variation between institutions in perioperative performance in the context of these drugs.
James Douketis: I believe that this uncertainty justified the conduct of the study from a scientific and ethical point of view. Tell us a little about POISE-3, the 2 strategies that consisted of continuing or discontinuing ACEIs and ARBs. What exactly was the pre-, intra- and post-operative management?
Maura Marcucci: The study was designed to compare 2 strategies that we call hypotension avoidance and hypertension avoidance, to indicate the blood pressure alterations that each strategy attempted to avoid.
Both strategies included a pre-, intra-, and postoperative phase. In the strategy of avoiding hypotension, in the preoperative phase, ACEIs and ARBs were discontinued, and other hypotensive agents were continued according to a specific protocol. It was a stepwise protocol and drugs that control heart rate, for example, β-blockers, were prioritized.
In the intraoperative phase, patients had a specific target, mean arterial pressure target, that the anesthetists had to follow, which was ≥80 mm Hg.
Then, in the postoperative period, for the first 2 days, the same algorithm was used to manage chronic hypotensive drugs. Therefore, ACE inhibitors and ARBs were administered without the other hypotensive agents, according to the same algorithm.
In contrast, in the hypertension avoidance strategy, designed to resemble standard practice, all chronic hypotensive agents were continued in the perioperative phase, before and after surgery. In the intraoperative phase, the mean arterial pressure goal was ≥60 mm Hg.
Now, these were the planned strategies. During the study we saw situations that were not 100% compliant with key design strategies. There was no full and ideal adherence to the assigned strategy. Adhesion was good, especially intra- and postoperatively, but was not 100%.
So we did additional analyzes at one point to try to understand the main results of the trial—as you know, no difference was demonstrated between the 2 strategies—and we wondered if the lack of difference in major vascular complications between the 2 groups was because of the lack of optimal adhesion. We did not find any association. We did not find a dose-response relationship between the level of adherence and the results of the study. We found no significant difference—or, in fact, any—between the 2 groups in the centers or patients with better adherence to the 2 assigned strategies.
James Douketis: Imagine a doctor asking you: “Dr. Marcucci, thank you for the study and the results. The result is neutral. How would you manage a preoperative patient treated with ACEIs or ARBs, about to undergo, say, an inguinal hernia repair? What would be your approach based on the knowledge acquired in the study?”
Maura Marcucci: I want to emphasize that the key conclusion for practice is that the 2 strategies we compared are reasonable. They are just as safe.
How can test results be individualized? I can do this based on my own clinical judgment. I mean, of course, if a patient comes to surgery and his blood pressure is very high, there is no reason to discontinue hypotensive medications, including ACEIs or ARBs. Or if the anesthetist orders to stop the hypotensive agents, but the patient has forgotten to do so and arrives at surgery after taking his hypotensive agents, there is no reason to postpone or cancel the surgery.
On the other hand, if the patient comes to surgery with low blood pressure—especially if it is particularly low compared to his usual blood pressure, which means he will not tolerate chronic hypotensives as well as before—I will stop the hypotensives. It is also a reasonable strategy.
When I talk about individualization, I mean that probably the subgroup analyzes for now do not demonstrate a specific subgroup of patients for whom one of the strategies is better. But I also mean that I can most likely follow the preferences and values of patients and doctors.
Many times we find patients who become jealous of their hypotensive medications, or their chronic medications in general. If you tell them, “We have to stop the drug on the day of surgery,” and they say, “No, I don’t want to. I’m afraid,” that’s fine. You can continue.
On the other hand, if the anesthetist firmly believes that ACEIs or ARBs should be discontinued because he has had many patients with a drop in intraoperative blood pressure due to having continued ACEIs or ARBs, it is okay to discontinue these drugs.
James Douketis: To summarize, I think the essay gives us a very important message: that neither approach is associated with harm reduction, but the most important thing is that they do not cause harm either. There is some flexibility that, as you said, can be based on the patient’s individual values and clinical judgment. I think it’s an important message because the question comes up so often and I think doctors have a very clear answer.
Dr. Marcucci, we look forward to hearing more about your work in this area from some of the POISE-3 subanalyses, and again, congratulations on this important landmark study.
Maura Marcucci: Thank you very much, Jim. I thank you for the opportunity.