Heart Injuries Suggest Reconsideration of Holding BP Meds for Surgery

The practice of taking some patients briefly off their antihypertensive medications before non-cardiac surgery did not work as intended, and in fact led to excess acute hypertension in the SPACE trial.

Myocardial injury rates were no worse, even numerically better, for people randomized to stay on their renin-angiotensin system (RAS) inhibitors (41.3%) compared with peers subject to individualized, pharmacokinetically-based withdrawal of these common medications in preparation for elective surgery (48.3%; OR 0.77, 95% CI 0.45-1.31), reported Gareth Ackland, PhD, of Queen Mary University of London, and SPACE collaborators.

Withdrawal of RAS inhibitors did not significantly affect the incidence of hypotension (9.3% vs 8.4%), but it was associated with more acute hypertension (>180 mmHg) within 48 hours of surgery (12.4% vs 5.3%; OR 0.4 for continued therapy, 95% CI 0.16-1.00), they stated in the European Heart Journal.

A combined endpoint counting both adverse hypotension and hypertension events favored the group continuing RAS inhibitor therapy (13.0% vs 21.7%).

“We also noted that the relative risk of myocardial injury between groups, if replicated in a larger clinical effectiveness trial, may indicate significant benefits to continuing RAS inhibitors during the peri-operative period,” Ackland’s group wrote.

RAS inhibitors, namely angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), are widely used drugs for high blood pressure (BP) and heart failure. To prevent intra-operative hypotension, many clinicians choose to halt their use before surgery — though the scientific evidence for this practice is lacking.

Study authors noted that hemodynamic instability is associated with peri-operative myocardial injury, which is known to be a frequent complication of noncardiac surgery. Prior research has associated peri-operative myocardial injury with a greater risk of subsequent mortality even if caught early.

“The SPACE randomized trial shows that continuing these medications does not cause much hypotension and does not worsen cardiovascular complications. The implication is that these antihypertensive medications can be continued through the morning of surgery just like most other drugs,” commented Dan Sessler, MD, of Cleveland Clinic.

“This important trial provides useful guidance to clinicians managing surgical patients,” Sessler told MedPage Today.

Guidelines acknowledge the clinical uncertainty regarding RAS inhibitors during surgery. Only observational studies have found that they cause serious hypotension during anesthesia, according to Sessler, who wasn’t involved in the study.

“The lack of consistency in when RAS inhibitors have been stopped before — and restarted after — noncardiac surgery explains, in part, the considerable variability in international recommendations for the management of RAS inhibitors in surgical patients,” Ackland and colleagues added.

They highlighted the conditions for ACE inhibitor and ARB withdrawal and resumption in the SPACE trial:

• RAS inhibitors with a duration of action ≥24 hours were discontinued 48 hours prior to surgery. Shorter-acting drugs were stopped on the morning of the day before surgery.
• RAS inhibitors were restarted after surgery on the morning of postoperative day 2, or delayed if systolic BP was <90 mmHg in the preceding 12 hours, vasoactive therapy was required to maintain BP, and/or if acute kidney injury had been sustained.
• Resumption or continuation of RAS inhibitors did not involve dose modifications.

SPACE was a randomized trial conducted at six U.K. centers in 2017-2021. Participants were ages ≥60, who were scheduled for elective non-cardiac surgery requiring general anesthesia for more than 120 minutes. Exclusion criteria included myocardial infarction within the 3 months preceding surgery and patients taking RAS inhibitors for left ventricular dysfunction.

Investigators ultimately had 262 participants randomized to stop or continue the RAS inhibitors they were already on for existing medical conditions.

The combined trial cohort had a median age of 71, with 48% being women and nearly all white. RAS inhibitors were prescribed for hypertension in 97% of patients, and those with heart failure comprised fewer than 10% of the study population. Diabetes mellitus was diagnosed in 29%.

Before randomization, both groups showed similar systolic (138 vs 140 mmHg) and mean arterial BP (95 vs 97 mmHg) in the pre-assessment clinic.

The primary endpoint, myocardial injury, was defined as plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 hours after surgery, or a ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L in blood samples collected immediately before the induction of anesthesia.

What constitutes intraoperative hypotension is a subject of controversy, as there have been various arbitrary definitions proposed based on absolute BP thresholds or relative BP decreases, and a “true” baseline BP can be difficult to assess in the surgical setting. More recently, some are favoring a personalized definition of hypotension based on cerebral blood flow autoregulation monitoring.

In the present study, hypotension was judged by each attending clinician as a case requiring pressor vasoactive medication delivered via central venous access.

Study authors acknowledged the open-label design of SPACE and its insufficient power for detecting between-group differences in cardiovascular events or mortality. Results may not necessarily apply to other racial or ethnic groups, they also cautioned, urging confirmation from future studies.

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