Alicia Ault

November 04, 2016

CHICAGO — For patients undergoing noncardiac surgery, rates of death, stroke, and myocardial injury are reduced when angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are discontinued 24 hours before the procedure, according to new research.

"We believe clinicians should consider withholding ACE inhibitors and ARBs in major noncardiac surgery patients in the 24 hours before surgery," said investigator Pavel Roshanov, MD, an internal medicine resident at McMaster University in Hamilton, Ontario, Canada.

Results from VISION — the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation — were presented here at Anesthesiology 2016 from the American Society of Anesthesiologists, and published online simultaneously.

ACE inhibitors and ARBs are both known to cause hypotension during anesthesia, but it has not been determined whether they lead to adverse outcomes.

VISION involved 14,687 patients 45 years and older who were undergoing inpatient noncardiac surgery. The study was conducted at 12 centers in eight countries in Asia, Australia, Europe, and North and South America from 2007 to 2011.

The 30-day primary outcome was a composite of death from any cause; myocardial injury after noncardiac surgery, indicated by any peak non-high-sensitivity cardiac troponin T level of at least 0.03 ng/mL resulting from myocardial ischemia; and stroke.

Of the 4802 patients taking ACE inhibitors or ARBs, 1245 (26%) stopped 24 hours before surgery and 3551 (74%) did not.

The composite end point was met by 150 patients who stopped taking their medications and by 459 of those who continued (12.0% vs 12.9%).

Patients who stopped medications were less likely than those who did not to meet the composite outcome (adjusted relative risk [aRR], 0.82; 95% confidence interval [CI], 0.70 - 0.96; P = .01).

Those who stopped were also at lower risk for intraoperative hypotension than those who did not (aRR, 0.80; 95% CI, 0.72 - 0.93; P < .001).

Patients with intraoperative hypotension were more likely to meet the composite outcome than those without (aRR, 1.23; 95% CI, 1.03 - 1.47; P = .03), as were those with postoperative hypotension (aRR, 2.01; 95% CI, 1.72 - 2.33; P < .001).

The findings confirm that hypotension is predictive of injury, Dr Roshanov reported.

Unclear Why Meds Stopped

Almost 7000 patients were taking one or more antihypertensives in the week before their procedure. In fact, about 60% the patients were taking one medication, about 31% were taking two, and about 9% were taking three or more.

It is not clear in all cases why patients stopped or continued taking their medications before surgery. And for those taking multiple therapies, usually just a single antihypertensive was stopped.

Patients who stopped their medications were less likely than those who continued to have very high preoperative blood pressure, less likely to undergo major urogenital surgery, and more likely to undergo major general and urgent or emergency surgery.

It is likely that many of the patients made their own decisions about whether to stop or continue their medications, Dr Roshanov told Medscape Medical News.

Demographic, clinical, or surgical information explaining the discontinuation was available for only 0.62% of the patients. The most common reason for stopping was the center's practice pattern, accounting for 6%.

Among countries, rates of discontinuation ranged 9% to 44%. The differences seem to reflect "local variation in practitioner preference," Dr Roshanov said.

More Guidelines Needed?

This wide variation might be an indication that physicians need concrete guidance on when to withhold medications. "I do think that guideline development committees should re-evaluate this question in light of new evidence," said Dr Roshanov.

In fact, on the basis of the VISION findings, guidelines on perioperative management issued by the Canadian Cardiovascular Society now suggest withholding ACE inhibitors and ARBs, he reported.

Continuing these medications does cause hypotension and does worsen outcomes.

These results "show that continuing these medications does cause hypotension and does worsen outcomes," said Daniel Sessler, MD, Michael Cudahy Professor and chair of the Department of Outcomes Research at the Cleveland Clinic.

He said he sees no need for more committee work. Now that these results are available, "we can give more accurate and specific guidance," he explained. Patients "should stop the medication 1 day before surgery."

Even more definitive data might be on the way. The VISION investigators plan to repeat their analysis to evaluate renal outcomes. "If the signal remains consistent, I think it's worthwhile to consider conducting a full randomized controlled trial," Dr Roshanov said.

Roche Diagnostics provided funding and provided the troponin assays used in the study. Dr Roshanov and Dr Sessler have disclosed no relevant financial relationships. P.J. Devereaux, MD, PhD, principal investigator of VISION from McMaster University, reports receiving research funding from Roche Diagnostics and Abbott Diagnostics.

Anesthesiology 2016 from the American Society of Anesthesiologists. Presented October 23, 2016.


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