Hot Line: Renin-angiotensin system inhibitors before non-cardiac surgery – stop or not?
31 Aug 2024
Discussing why the STOP-or-NOT trial was conducted, Professor Matthieu Legrand (University of California at San Francisco - San Francisco, USA) said: “Many patients who undergo major surgery are receiving chronic treatment with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). Due to a lack of conclusive data from randomised trials, whether to stop renin-angiotensin system inhibitors (RASIs) before non-cardiac surgery is uncertain. RASI continuation might lead to intra-operative hypotension, which could result in post-operative cardiovascular events and acute kidney injury (AKI). On the other hand, RASI discontinuation might cause post-operative hypertension, heart failure or arrhythmias.” The STOP-or-NOT trial was conducted to compare major post-operative outcomes if RASIs were stopped or not stopped.
In this open-label trial conducted in France, patients scheduled for elective major non-cardiac surgery who were chronically treated with ACEIs or ARBs for at least 3 months before surgery were randomised to continue RASIs until the day of surgery or to discontinue them 48 hours prior, i.e. to receive their last dose 3 days before surgery. In both groups, it was recommended that RASIs were resumed as soon as possible after surgery.
The primary endpoint was a composite of all-cause mortality and major post-operative complications within 28 days after surgery, defined as post-operative major cardiovascular events (including acute myocardial infarction, arterial or venous thrombosis, stroke, acute pulmonary oedema, cardiogenic shock, acute severe hypertension crisis and de novo cardiac arrhythmia requiring therapeutic intervention), sepsis or septic shock, respiratory complications, unplanned ICU admission or readmission, AKI, hyperkalaemia or need for surgical reintervention.
In total, 2,222 patients were randomised. The mean age was 67 years and 65% were male. Ninety-eight percent of patients were treated for hypertension, 9% had chronic kidney disease, 8% had diabetes and 4% had heart failure. Overall, 46% were treated with ACEIs and 54% were treated with ARBs at baseline.
There was no difference in the primary endpoint.
The rates of all-cause mortality and major post-operative complications were the same (22%) in the discontinuation group and the continuation group (risk ratio [RR] 1.02; 95% CI 0.87–1.19; p=0.85). The effect of the discontinuation vs. continuation of RASIs on the risk of post-operative complications was consistent across subgroups.
Episodes of hypotension during surgery occurred in 41% of patients in the discontinuation group and 54% of patients in the continuation group (RR 1.31; 95% CI 1.19–1.44). The median (IQR) duration of hypotension with a mean arterial pressure <60 mmHg was 6 (4–12) minutes in the discontinuation group and 9 (5–16) minutes in the continuation group (mean difference of 3.7 minutes; 95% CI 1.4–6.0). There were no other differences in trial outcomes.
“Our results may now be used within guideline recommendations, which are generally weak. Given the lack of difference, both strategies appear acceptable, indicating that a tailored approach to RASI continuation could be used. A discontinuation strategy may be considered if there is a particular concern for hypotension, while continuation may be preferred in patients who are worried about stopping their medication or for practical purposes,” concluded Prof. Legrand.
