Researchers at Toronto General Hospital used data from more than 61,000 patients to compare people who took ACE inhibitors with those who did not, and found that being on the blood pressure medication long-term leading up to noncardiac surgery was associated with lower 30-day mortality.

When they looked more closely at the ACE inhibitor group, they found that those who chose to stop taking the drugs a few days prior to surgery, and delayed restarting it, fared no better than those who took the drug up to the morning of the procedure, and resumed once they were stable.

“Maintaining ACE inhibitors prior to surgery might be of some benefit,” said study author Jason Toppin, MD. “And they definitely do not cause any problem.”

Dr. Toppin’s group presented its findings at the 2011 annual meeting of the Society of Cardiovascular Anesthesiologists (abstract 64).

Decisions Based On Unsatisfying Data

Previous small, retrospective studies had suggested that patients who take ACE inhibitors in the perioperative period are at higher risk for renal failure, hypotension, cardiac events such as myocardial infarction and even death. The reasoning, Dr. Toppin explained, was that any drug that lowers blood pressure might cause problems when combined with either anesthesia or other issues that exacerbate hypotension.
But when he and his colleagues took a closer look at the studies, they felt the researchers did not adequately control for differences between those on and off the drugs. People taking ACE inhibitors are generally sicker, he explained, so comparison studies have to be careful to match them with people who have the same levels of underlying disease.

So Dr. Toppin and his team scanned the hospital’s surgical booking center for all patients undergoing noncardiac surgery between 2003 and 2008. They identified 61,420 patients, 7,339 (12%) of whom were taking ACE inhibitors—or, less commonly, angiotensin receptor blockers (ARBs)—at the time of surgery. They then isolated about 7,200 patients on the drugs and compared them with the same number not taking the medications, taking care to match patients on more variables than had prior studies, such as cardiac failure, renal function and other risk factors, Dr. Toppin said.
They found that those taking ACE inhibitors or ARBs experienced a statistically significant reduction in mortality (odds ratio, 0.54) within the 30 days after surgery. Specifically, 1.4% of those not taking the medications died, compared with about 0.5% of those on ACE inhibitors (P<0.0001).

When they looked within the group taking ACE inhibitors, stopping the drug prior to surgery and for a few weeks afterward was not associated with any better outcomes.

These findings mirror what Arthur Wallace, MD, PhD, of the University of California, San Francisco and his colleagues have seen: Taking ACE inhibitors before surgery poses no added risk.
“When we have looked, it’s hard to show that people with ACE inhibitors have more hypotension during surgery when you give them the drug,” Dr. Wallace told Anesthesiology News.

The finding makes sense, Dr. Wallace added, because if people need the drug to go about their daily lives, they should need it during a time of added stress, such as surgery. “It is hard to show that taking away a good drug is good for you,” he said.
“It just goes back to why people are on them,” agreed Dr. Toppin. “It’s a drug that is associated with beneficial effects in these high-risk patients.”

In 2008, the American College of Physicians issued recommendations on the perioperative management of patients with congestive heart failure, which stated that clinicians should “consider holding or reducing” the usual dose of ACE inhibitors the day of, and for up to 24 hours prior to, elective surgery (http://pier.acponline.org/mcpp/pdf/periopr867.pdf).

Still, the decision to stop or continue ACE inhibitors prior to surgery depends on the individual and institution, Dr. Toppin said. However, some patients do halt their medication over fears of ill effects, based on the results from prior studies. He said he typically asks patients to continue their ACE inhibitors until the morning of surgery, then restart once they are stable.

Yet, the real understanding of the benefits or risks associated with ACE inhibitors will only come after prospective studies, Dr. Toppin cautioned. “We still think the definitive answer still lies in doing a prospective study.”

Researchers should not stop with ACE inhibitors, added Dr. Wallace, who is chief of anesthesia at the San Francisco VA Medical Center. Some regular aspirin-takers stop the drug before surgery, out of fear of excess bleeding, he said, and some hospitals even halt b-blockers for patients during the perioperative period, despite research showing this practice may be harmful. “We need to identify which medicines you need to keep going, and which medicines need to be stopped before surgery. It’s incredibly important.”