Targeting higher intraoperative blood pressures in patients undergoing non-cardiac surgical procedures did not reduce postoperative complications such as acute myocardial injury or 30-day major adverse cardiovascular events (MACE), according to results from a single-center randomized, controlled trial published in the Journal of the American College of Cardiology.
“Targeting an MAP ≥75 mm Hg universally in patients at cardiovascular risk undergoing major noncardiac surgery was not associated with a reduction in the incidence of 30-day MACE/[acute kidney injury] AKI and/or acute myocardial injury on [postoperative days] PODs 0-3 or the incidence of 1-year MACE compared with standard intraoperative BP management per the current 2014 ESC/ESA Clinical Practice Guidelines on Noncardiac Surgery,” wrote Patrick M. Wanner, MD, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Switzerland, and colleagues.
“Despite the strong association of intraoperative hypotension with postoperative adverse cardiovascular outcomes, our data are not indicative of a large reduction in the incidence of such events and cannot rule out the absence of a reduction in postoperative MACE/AKI when universally targeting higher intraoperative BP,” they added.
For this study, Wanner and fellow researchers enrolled 458 adult patients (mean age: 69-70 years; 81%-83% male) at cardiovascular risk who were undergoing major noncardiac surgery to an intraoperative MAP target of ≥60 mmHg (control group) or ≥75 mmHg (MAP ≥75). The most common procedures were vascular surgeries (71% of controls, 63% of MAP target ≥75 mmHg).
The primary outcome was acute myocardial injury on postoperative days 0-3 and/or 30-day MACE/acute kidney injury (AKI), including acute coronary syndrome, congestive heart failure, coronary revascularization, stroke, AKI, and all-cause mortality, and secondary outcome was 1-year MACE.
The incidence of the primary outcome in the MAP ≥75 group was 48%, compared with 52% in the control group (risk difference: −4.2%; 95% CI: −13% to +5%), with AKI being the primary contributor. Researchers also found the following similar between-group results:
- Acute myocardial injury in 15% and 19%, respectively (risk difference: −4.4%; 95% CI: −11% to +2.5%).
- MACE/AKI in 45% versus 46%.
- Acute kidney injury present in 43% versus 46% (risk difference: −3.4%; 95% CI: −13% to +5.8%).
The incidence of the secondary outcome (1-year MACE) was also similar in both groups, at 17% versus 15%, respectively (risk difference: +2.7; 95% CI: −4% to 9.5%).
In those in the MAP ≥75 group, cumulative intraoperative duration with a MAP of ˂65 mmHg was significantly shorter compared with control (median: 9 versus 23 minutes, respectively; P˂0.001). Wanner and colleagues did find, however, a significant association between longer intraoperative time of hypotension (MAP ˂65 mmHg) and the primary composite endpoint (risk difference: +21%; 95% CI: +12% to +30%), and with 1-year MACE (risk difference: +9.8%; 95% CI: +3.1% to +17%), the latter of which was confirmed with proportional hazards regression (HR: 1.98; 95% CI: 1.22-3.21).
Importantly, Wanner et al also performed sensitivity analyses due to the high incidence of AKI, which was 46% in the control group. These showed no significant differences in the primary outcome with 30-day MACE defined without AKI (risk difference: −4.4%; 95% CI: −11% to +2.7%), with lab criteria (risk difference: −2.5%; 95% CI: −11% to +6.5%) and defined per protocol (risk difference: −4.2%; 95% CI: −13% to +5%).
“Wanner et al similarly included AKI, which proved to be by far the most common composite component. In fact, a remarkable 97% of all composite outcomes included AKI. The next most common outcome was MINS, which contributed to 40% of the outcomes. The difficulty is that two-thirds of the AKI was stage 1 (technically designated “risk” rather than injury). Stage 1 AKI is more important than generally appreciated, and about one-third persists long-term or worsens, but it is nonetheless far less serious and far more common than other elements in the Wanner composite. The Wanner composite therefore largely evaluates renal injury, mostly stage 1,” wrote Daniel I. Sessler, MD, of the Department of Outcomes Research, Cleveland Clinic, and Timothy G. Short, MD, of the University of Auckland, New Zealand, in their accompanying editorial.
“Fortunately, Wanner et al provide a sensitivity analysis that excluded AKI from their composite. The incidence of the diminished composite was reduced by 60%, from 45% to 18%, because no component besides MINS contributed substantively,” they added.
Upon a post hoc analysis, researchers found that both postoperative AKI (OR: 4.96 [95% CI: 1.48-22.5) and acute myocardial injury (OR: 3.19 [95% CI: 0.15-26.3) were significantly and independently associated with 1-year mortality in the whole study population.
“What, then, should we conclude from the available information? The association between hypotension and various complications seems clear, and has now been demonstrated by many investigators using various datasets. The remaining question is the extent to which the association is causal,” queried Sessler and Short.
“The trial by Wanner et al evaluates causality and is thus welcome. But, although the primary outcome did not differ by statistically significant or clinically meaningful amounts in the treatment groups, clinicians should not interpret the results as ’ruling out’ an important effect of hypotension on serious complications. That conclusion would require a much larger trial,” they added, noting that both the large, randomized POISE-3 and GUARDIAN trials have been initiated to do just that.
“In coming years, we should thus have robust information about the extent to which the association between hypotension and major organ injury is causal, and at what thresholds. In the meantime, clinicians would be prudent to avoid hypotension when practical,” concluded Sessler and Short.
Study limitations include the choice of a universal MAP target ≥75 mmHg may have been inadequate, that researchers compared two MAP targets rather than two BPs, the unbalancing effect of the high incidence of AKI on the incidences of the composite primary outcome, that the study was not powered to detect treatment effect on 1-year outcomes, and that findings on long-term outcomes are exploratory in nature. Wanner et al also urged caution in interpreting individual subcomponents of the composite endpoint.
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Targeting an MAP ≥75 mm Hg universally in patients at cardiovascular risk undergoing major noncardiac surgery was not associated with a reduction in 30-day MACE/AKI and/or acute myocardial injury postoperatively, or the incidence of 1-year MACE compared with standard intraoperative BP management.
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Despite a 60% reduction in hypotensive time with MAP <65 mmHg, no significant reductions in acute myocardial injury or 30-day MACE/AKI occurred.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
This study was supported by grants from the Swiss National Science Foundation, the Swiss Heart Foundation and the Scientific Commission of the Cantonal Hospital St. Gallen, Switzerland.
Wanner has received grants from the Swiss Heart Foundation.
Sessler has served as a consultant for and his department has conducted research funded by Edwards Lifesciences; and has served on advisory boards and has equity interests in Sensifree and Perceptive Medical.
Short has served as a consultant for Beckton Dickinson; and has conducted commercial research for Roche Pharmaceuticals and Boehringer Ingelheim.
Cat ID: 159
Topic ID: 97,159,730,914,192,925,159
