ACEi: Captopril, Enalapril, Fosinopril, Imidapril, Lisinopril, Perindopril, Quinapril, Ramipril, Trandolapril
AIIRA: Azilsartan, Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan
Issues for Surgery
Potential increase in major adverse cardiovascular events if omitted.
Potential intraoperative hypotension, including refractory hypotension, if continued, which may increase the risk of ischaemic cardiovascular events.
Advice in the Perioperative period
Perioperative continuation or cessation of ACEi / AIIRA remains a contentious issue as there is a lack of high quality evidence on which to base a recommendation (for a discussion of the arguments for and against pre-operative omission of ACEi / AIIRA see Further Information). Until high quality evidence becomes available it is recommended that local consensus is reached regarding the pre-operative management of patients on ACE / AIIRA (including combination products). A practical approach is to omit the ACEi / AIIRA on the morning of surgery, although some centres may opt to omit them up to 48 hours pre-operatively.
Combination products: -
Consideration should be given to prescribing the components of combination products as separate medicines perioperatively. However, some components of combination products do not exist as individual medicines (e.g. hydrochlorothiazide, sacubitril). If there is any doubt about the need to continue / withhold component agents of a combination product, advice should be sought from an Anaesthetist.
If patient has taken any dose(s) in previous 24-48 hours, inform Anaesthetist as potential for intraoperative hypotension (see Interaction(s) with Common Anaesthetic Agents).
If ACEi or AIIRA has been continued pre-operatively, monitor for intraoperative hypotension. If this occurs, treat according to advice below (see Interaction with Common Anaesthetic Agents).
If stopped prior to surgery, restart post-operatively as soon as blood pressure and volume are stable1. It is important that the Surgical Team ensure that the patient is aware when to restart the ACEi / AIIRA post-operatively to avoid unintentional drug cessation2.
Monitor renal function post-operatively. Consider withholding ACEi / AIIRA post-operatively if patient develops acute kidney injury (AKI).
Monitor blood pressure (BP) – consider omitting if BP low.
Interaction(s) with Common Anaesthetic Agents
Marked hypotension during anaesthetic induction has been seen in patients taking ACEi or AIIRA3. Hypotension secondary to ACEi / AIIRA usually occurs within 30 minutes of induction of anaesthesia and is more common in patients also taking diuretics4. The frequency and magnitude of intraoperative hypotension is greater in patients taking AIIRA than ACEi and also appears to be less responsive to ephedrine and phenylephrine3, 4.
Treatment of Hypotension
Interaction(s) with other Common Medicines used in the Perioperative Period
ACEi/AIIRA can cause hyperkalaemia; the risk is further increased with concomitant use of the following medications3, 5: -
If concomitant treatment is required – monitor serum potassium, particularly if there is other risk factors for hyperkalaemia e.g. renal impairment.
Argument for Stopping Pre-operatively
A meta-analysis with 4206 patients who continued and 1816 patients who withheld ACEi / AIIRA before surgery showed no difference in all-cause mortality or MACE between the two groups. However, there was a marked heterogeneity between studies and the meta-analysis was underpowered for all reported outcomes. Continuation of ACEi / AIIRA was associated with a significantly increased risk of intraoperative hypotension (29.9%), but not postoperative hypotension, compared to those who stopped ACEi / AIIRA (23.4%)6.
Argument for Continuing Pre-operatively
Even if ACEi / AIIRA are stopped pre-operatively, hypotension can still occur3, 4; it is likely that the hypotensive effect may persist for some time after stopping therapy because of persistent tissue-based activity4. Failure to take into account the variable durations of action of ACEi / AIIRA may be a confounding factor when studying the effects of stopping pre-operatively7.
Meta-analysis of data from patients who continued ACEi / AIIRA on the day of cardiac and non-cardiac surgery found that hypotension was more likely with continuation (but most cases were sensitive to intravenous fluids and vasoconstrictors); however, continuation of ACEi / AIIRA did not increase the incidence of post-operative complications such as myocardial infarction, cerebrovascular accident, AKI or death2.
In cardiac surgery the perioperative administration of ACEi / AIIRA has been associated with a lower risk of AKI. In an observational study of 949 patients undergoing non-cardiac surgery no difference in incidence of AKI was observed between patients who continued or withheld ACEi / AIIRA pre-operatively, therefore withholding ACEI / AIIRA does not protect against development of post-operative AKI8.
Recommendations of Reputable Societies
European Society of Cardiology (ESC) & European Society of Anaesthesiology (ESA)
American College of Cardiology (ACC) & American Heart Association (AHA)
Canadian Cardiovascular Society (CCS)
SPACE Clinical Trial
Stopping Perioperative Angiotensin II Converting Enzyme inhibitors and/or angiotensin receptor blockers in major non-cardiac surgery (SPACE) is a phase III, randomised controlled trial (ISRCTN17251494) aiming to establish if perioperative continuation of ACEi / AIIRA reduces the risk of myocardial injury. Patients randomised to the discontinuation arm will stop their ACEi / AIIRA 24-48 hours pre-operatively, depending on its duration of action. The trial will run until January 2021 with publication of results soon after11.