No Difference Between Hypotension-Avoidance and Hypertension-Avoidance Strategies for Reducing Post-Surgical Adverse Events

In this video, Maura Marcucci, MD, MSc, discusses her study's surprising results, which showed no differences between hypotension-avoidance and hypertension-avoidance strategies for decreasing adverse events after noncardiac surgery.

Additional Resource:

  • Marcucci M, Painter TW, Conen D, et al. Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery: An International Randomized Controlled Trial. Ann Intern Med. 2023;176(5):605-614. doi:10.7326/M22-3157.


Maura Marcucci, MD, MSc is an assistant professor in the Departments of Health Research Methods, Evidence, and Impact (HEI), and Medicine, at McMaster University (Hamilton, Ontario, Canada).


Consultant360: What was the impetus for this research? Why now?

Maura Marcucci, MD, MSc: Over 300 million patients undergo non-cardiac surgery every year, and unfortunately, many of these patients will still experience cardiovascular complications close to the time of surgery. Many of these patients also experience hemodynamics abnormalities, and hemodynamics abnormalities have been linked with major cardiovascular complications after non-cardiac surgery. In particular, a quarter of these patients will experience hypertension intraoperatively, and also postoperatively. And hypertension has been linked with mortality and major vascular outcomes after non-cardiac surgery.

The majority of patients undergoing non-cardiac surgery are chronically on anti-hypertensive medications although practice varies across institutions, these medications are commonly continued perioperatively, however, there has been uncertainty about how to manage chronic anti-hypertensive medications. There was some preliminary evidence from observation studies and small randomized control trials suggesting that holding ACE inhibitor or ARBs around the time of surgery may reduce perioperative hypertension, but also some other evidence suggesting that continuing chronic beta blockers could prevent major cardiovascular complications after non-cardiac surgery and even intraoperatively, there was uncertainty regarding what blood pressure target would be beneficial in terms of reducing hypertension and reducing major vascular complications. So there was the need for a definitive trial and that was meant to be POISE-3.

C360: How does this study fill a current gap in our knowledge?

Dr Marcucci: Yeah, the gap was really like to try to answer, I would say two questions that commonly confront physicians that are taking care of patients undergoing non-cardiac surgery. On one side, what to do intraoperatively, so what target of blood pressure has benefits in terms of vascular complications, and then perioperatively, so in the time leading to surgery and in the early postoperative time, what to do with patient's chronic anti-hypertensive medications.

C360: Did the no difference outcome between the two avoidant strategy groups, even after looking at compliance and performing a subgroup analysis, surprise you?

Dr Marcucci: I mean, of course it surprised us. We were hypothesizing a difference between the two strategies, what we call the hypotension avoidance and the hypertension avoidance strategy. So we definitely wanted to dig a little bit more into why we found no difference. As you mentioned, the first of course, possible potential explanation again came to our mind was it probably it was like the non-optimal compliance, the reason why we did not see a difference. And we did, as you say, a number of post hoc analysis and we found that there was no dose effect relationships between the degree of compliance with the assigned strategies and the effect on our primary outcomes. So we didn't see a difference or a greater difference between the two strategies on the primary outcome in centers at greater compliance. On the other side, the other potential explanation, which turned out to be probably the real one, was that maybe the two strategies, the way we designed the two strategies even we were hoping to see a difference, in fact did not have a major impact on hemodynamics.

So we could not see a difference in clinical outcomes because the two strategies were not different in terms of hemodynamics. When I say hemodynamics, I mean like differences in blood pressure, heart rate at certain moments, but also difference in the occurrence of major hemodynamic events like what we call clinically significant hypertension. We did see a difference in clinically significant hypertension between the two strategies, but only intraoperatively when we know hypotension events have a shorter duration, usually anesthetists in the OR tend to monitor and are able to act on hypotension very quickly. And so we did not see a difference on postoperative hypotension. And we know that postoperative hypotension lasts longer and there is evidence suggesting that it's really the postoperative hypotension, the hypotension, and there's the major prognostic significance. So very likely we did not see a difference between the two strategies because the two strategies did not produce an important differential effect on hemodynamics. So once we dug into that, the results surprised us a little less.

C360: What gaps in our knowledge still remain, and what kind of studies are needed to fill those gaps?

Dr Marcucci: I think two different types of codes, like remaining within the research question that POISE-3 tried to address. We did a number of subgroup analysis that showed consistent results with regarding the difference in the primary outcome, no difference, not even in subgroups based on whether the patients were on one chronic anti-hypertension medication versus more anti-hypertensive medications or whether a patient started with a lower or higher blood pressure coming to surgery. But there's still more analysis that we could do to think to explore whether there are some subgroups that would still benefit from one strategy compared to the other. So that's one gap that we can at least explore. The second thought though is that what you were alluding to, so POISE-3 did not demonstrate that hypotension doesn't matter. It just demonstrated that the two strategies that we compared, they did not produce a difference in hemodynamics and in vascular outcomes. But there are certainly other interventions that we could explore and study and design and evaluate intervention that could tackle perioperative hemodynamics in a different way, in a substantial way, and then eventually lead to a difference also in vascular outcome. So there is further research that is needed to identify those potential effective interventions.

C360: Looking ahead, what interventions could be investigated next?

Dr Marcucci: So there could be potentially a pharmacological interventions. Just to give you an example, you might remember POISE-1. POISE-1 was a study in which patients that were naive to beta blockers were randomized to receive perioperative beta blocker or not. In that case we did see a substantial difference between the two groups, hemodynamics and in vascular outcomes. So there are pharmacological strategies that might work and might eventually produce such a difference or non-pharmacological strategies. Our group is now working on studying what will be more what are the potentials of intensifying the postoperative monitoring. As I mentioned, the postoperative phase of the whole perioperative moment is a delicate one currently. There is a huge difference between the intensity of monitoring that we are able to achieve intraoperatively and what we can do postoperative where we're still manually intermittently measuring vitals and monitoring this patient. So our study, our group is actually currently focusing on what could be the role of a more intense continuous postoperative monitoring in terms of vascular outcomes.

C360: What’s the take home message from this study?

Dr Marcucci: As I mentioned in the beginning as you said, okay, there was a surprise and in some way disappointment, but it's true that POISE-3 did provide an answer. A negative answer is an answer. So what POISE-3 is showing us is that on one side a target, an intraoperative target of a mean arterial pressure of 60 versus 80, they're both safe. So anesthesiologist could target either one. And perioperatively holding ACE inhibitor or ARBs and then continue the other anti-hypertensive medication based on a specific algorithm, which was our hypotension avoidant strategies versus just continue with all the anti-hypertensive medications did not produce a difference in hemodynamics and vascular outcome. So it's reasonable to follow either strategy and so the anesthesiologist's patients, other perioperative physicians, don't have that kind of headache of trying to figure out what to do best. They can still adopt either strategy and that is a way to individualize the management. If it's a patient that is very attached to their blood pressure medications, there are patients like that and they don't want to hold their blood pressure medication coming to surgery, that's absolutely okay. The anesthesiologist that wants to hold ACE inhibitor or ARBs because in their experience they do have an effect, that's okay. That's also reasonable strategy.