Perioperative MACCE Rate Falls but Ischemic Stroke Rises Among Noncardiac Surgery Patients

Overall rates of perioperative major adverse cardiovascular and cerebrovascular events have declined over the past decade in patients undergoing noncardiac surgeries in the United States, but as a new study shows, the incidence of perioperative ischemic stroke has risen in this population—a pattern even more striking considering the fact that national stroke trends have been falling.

“In the context of these national trends, the observed increase in the rate of perioperative ischemic stroke is a concerning finding that warrants additional study,” the authors, led by Nathaniel Smilowitz, MD (New York University School of Medicine, NY), write in JAMA: Cardiology.

Their paper was published online December 28, 2016.

Several contemporary trials such as CARP and POISE have tried to answer the question of how to best prevent adverse events during major noncardiac procedures, yet recommendations for solutions like preoperative coronary angiography, statins, and beta-blockers have changed over time, with today’s operators more likely to choose a more simplistic approach.

Reviewing 10,581,621 hospitalizations from the Nationwide Inpatient Sample between 2004 and 2013, Smilowitz and colleagues found a 3.0% rate of perioperative MACCE—including all-cause death, acute MI, and acute ischemic stroke—corresponding to an annual incidence of about 150,000 events throughout the country.

The frequency of MACCE decreased from 3.1% to 2.6% over time (P < 0.001 for trend), and this was driven by parallel drops in perioperative death and acute MI. However, the frequency of ischemic stroke rose over the same time period from 0.52% to 0.77% (P < 0.001 for trend).

Interestingly, perioperative MACCE occurred most often in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%), with multivariate analysis confirming each of these surgical types as independent predictors of MACCE compared with general surgery. Additionally, men were more likely than women to report adverse events (adjusted OR 1.17; 95% CI 1.16-1.18), and non-Hispanic black patients experienced higher MACCE rates than non-Hispanic white patients (adjusted OR 1.14; 95% CI 1.13-1.16).

No Causal Inference

The increase in ischemic stroke is the most surprising outcome of this study, senior author Sripal Bangalore, MD (New York University School of Medicine), told TCTMD. But because “this kind of analysis does not lend toward causal inference,” it is hard to know the reasons for the rise in strokes, he said, adding that it is possible that a previous emphasis on routine beta-blocker use in patients undergoing noncardiac surgeries contributed. Also, “it could merely be the fact that people are more savvy with diagnosis. There might be more imaging of these patients, and so you might just be picking up more strokes,” Bangalore said.

Additionally, Nicole Bhave, MD, and Kim Eagle, MD (University of Michigan Health System, Ann Arbor), suggest in an accompanying editorial that perhaps “patients subjected to anesthesia and fluid shifts may be prone to hypofusion-related strokes, or so-called watershed infarcts, more commonly than the general population.”

In the meantime, clinicians should concentrate more on reducing the risk of stroke for all patients, Bangalore said. “So far, we have only been focusing on reducing the risk of MI and death, and not much focus has been on stroke,” he commented.

Secondly, knowing that MACCE rates evidently vary among surgeries is “important because many times as clinicians when someone is sent for perioperative clearance, we tend to think of noncardiac surgery as this one big bucket. But there are differences based on the type of surgery, and I think if a patient is undergoing any of these higher-risk surgeries, we need to keep a closer tab on them.”

To gain information on why stroke rates have risen and ultimately work to lower them, Bangalore said not only should this study be replicated—perhaps “using a similar registry where there is more robust ascertainment as to why there is an increased risk of stroke”—but therapies should be investigated that actually reduce the incidence of stroke.

Bhave and Eagle also argue that more work should be done to understand the sex and ethnic disparities in outcomes even though “the gaps [in death and stroke rates] have narrowed slightly over time.”

Zeroing in on the transplant surgery events specifically, the editorialists attest that the study supports the view “that solid organ transplant surgery should be given equal consideration in perioperative risk assessment,” acknowledging that how these patients be risk stratified and treated to prevent MACCE is still unclear. One solution might be “multidisciplinary teams, including cardiologists who are invested in caring for organ transplant recipients both preoperatively and postoperatively,” they say.

For now, “the apparent increase in perioperative stroke is disconcerting,” Bhave and Eagle conclude, “but until the specific causes of this phenomenon are clear, we cannot develop useful countermeasures. Multicenter, multiregional collaboration will be essential to accomplish these goals.”