STOP-or-NOT trial tests whether renin-angiotensin system inhibitors should be stopped before non-cardiac surgery

Key take-aways 

• In the STOP-or-NOT trial, discontinuation of a renin-angiotensin system inhibitor (RASI) before non-cardiac surgery resulted in a similar rate of major post-operative complications compared with RASI continuation. 
• Rates of hypotension during non-cardiac surgery were higher and longer in the continuation group but this did not translate into a higher risk of post-operative complications. 
• Given the similar rate of post-operative complications, the choice of continuation/discontinuation could be made based on individual patient needs. 

London, United Kingdom – 30 August 2024: There was no difference in major post-operative complications in patients who continued vs. stopped renin-angiotensin system inhibitors (RASIs) before non-cardiac surgery, according to late-breaking research presented in a Hot Line session today at ESC Congress 2024.¹ 

“Many patients who undergo major surgery have a history of hypertension, diabetes or heart failure, and receive chronic treatment with a RASI, namely an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB).² Due to a lack of conclusive data from randomised trials, whether to stop 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).³ On the other hand, RASI discontinuation might cause post-operative hypertension, heart failure or arrhythmias.⁴ The STOP-or-NOT trial was conducted to clear up uncertainties and we showed no differences in major post-operative outcomes between stopping or not stopping RASIs,” explained Principal Investigator, Professor Matthieu Legrand of the University of California at San Francisco, USA. 

The STOP-or-NOT trial was an open-label, randomised, controlled trial conducted in 40 French centres. 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 1:1 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 RASI treatment was resumed as soon as possible after surgery when the oral route was deemed feasible. 

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 intensive care unit (ICU) admission or readmission, AKI, hyperkalaemia or need for surgical reintervention. Secondary endpoints included hypotension during surgery, all-cause mortality, episodes of AKI, post-operative organ failure, and hospital and ICU length of stay during the 28 days after surgery. 

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.  

For 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% confidence interval [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 (interquartile range) duration of hypotension with a mean arterial pressure below 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. 

“Results from the STOP-or-NOT trial 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 Professor Legrand. 

ENDS