UK: Study on Antihypertensive Medications and Non-Cardiac Surgery

Some patients are briefly taken off their antihypertensive medications before non-cardiac surgery. Now, a recent study published in the European Heart Journal suggests that this practice may not work as intended and may be harmful.

Findings from the SPACE trial revealed that discontinuing renin-angiotensin system (RAS) inhibitors before non-cardiac surgery failed to reduce myocardial injury and could raise the risk of clinically significant acute hypertension.

Study Details

In the randomized controlled trial involving 260 patients, preoperative BP was greater when RAS inhibitors were stopped. 48% of patients sustained myocardial injury after stopping RAS inhibitors, compared with 41% of patients who continued therapy. Hypertensive adverse events were more frequent when RAS inhibitors were stopped, without impacting hypotension rates.

Haemodynamic instability is linked with peri-operative myocardial injury, especially in patients receiving RAS inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). There is no clarity on whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury.

Therefore, Gareth L Ackland, Queen Mary University of London, Charterhouse Square, London, UK, and colleagues conducted a randomized, multi-centre, open-label trial to evaluate whether the discontinuation of RAS inhibitors would lessen myocardial injury and postoperative complications, whilst assessing whether avoidance of haemodynamic instability would reduce post-operative morbidity.

The study included patients aged ≥60 years undergoing elective non-cardiac surgery from 2017 to 2021. 262 were randomly assigned to either discontinue (n = 130) or continue RAS inhibitors (n = 132) prescribed for existing medical conditions in six UK centres. RAS inhibitors were withheld for different durations (2-3 days) before surgery, as per their pharmacokinetic profile.

Study Outcomes

The primary outcome of the study was determined as myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy.

• Myocardial injury occurred in 48.3% of patients randomized to discontinue, compared with 41.3% of patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77].
• Hypertensive adverse events were more frequent when RAS inhibitors were stopped [12.4%], compared with 5.3% who continued RAS inhibitors [odds ratio (for continuing): 0.4].
• Hypotension rates were similar when RAS inhibitors were stopped [9.3%] or continued [8.4%].

"The main finding of this trial was the similarity in the incidence of myocardial injury between patients who discontinued and continued RAS inhibitors during the peri-operative period," the researchers wrote. "However, patients who discontinued RAS inhibitors did experience more hypertensive events."

"These findings require confirmation in future studies," they concluded.

Reference

Ackland, G. L., Patel, A., Abbott, T. E., Begum, S., Dias, P., Crane, D. R., Somanath, S., Middleditch, A., Cleland, S., Brealey, D., Pearse, R. M., Ackland, G., Martin, T., Fernandez, M., Seidu, F., Pakats, M., Mahr, O., MacDonald, N., Dos Santos, F., . . . Harris, S. Discontinuation vs. Continuation of renin–angiotensin system inhibition before non-cardiac surgery: The SPACE trial. European Heart Journal. https://doi.org/10.1093/eurheartj/ehad716