Hold ACE inhibitors and ARBs before noncardiac surgery? Emerging evidence suggests a patient-specific approach

  • September 2026,
  • ;

ABSTRACT

Although withholding these drugs before noncardiac surgery reduces the risk of intraoperative hypotension, recent trials suggest that it leads to harm in sicker patients. An individualized approach is safest, particularly in patients with heart failure. This review examines the emerging evidence regarding the impact of pausing vs continuing these drugs on intraoperative hypotension, myocardial injury, acute kidney injury, and postoperative outcomes.

KEY POINTS

  • In patients who have been receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) for heart failure with reduced ejection fraction, it is reasonable to continue these drugs in the perioperative period, given the risk of cardiac decompensation if they are stopped.

  • The 2024 American College of Cardiology and American Heart Association guideline recommends a tailored approach—holding these drugs may have benefits in patients undergoing high-risk surgeries who are prone to hemodynamic instability.

  • Restart ACE inhibitors and ARBs as soon as possible after surgery to preserve their long-term therapeutic benefits, especially in patients with heart failure or chronic kidney disease.

The tide of opinion may be turning against routinely withholding angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) before noncardiac surgery, as doing so gives little clinical benefit and may cause harm. While we await clarity from definitive trials, clinicians will have to rely on their clinical judgment and make individualized decisions.

Around the world, more and more people are undergoing major noncardiac surgeries, and they are older and have more cardiac risk factors than patients in the past.1 Many of them have hypertension, diabetes, heart failure, and other comorbidities, for which they are receiving long-term treatment with inhibitors of the renin-angiotensin-aldosterone system, primarily ACE inhibitors and ARBs.

Approximately 25% of patients undergoing major noncardiac surgery develop perioperative hypertension, which, if uncontrolled, increases the risk of cardiovascular ischemia, cerebrovascular events, and bleeding.2 On the other hand, intraoperative and postoperative hypotension can also increase the risk for adverse cardiovascular and renal outcomes and even death.2 Therefore, clinicians need to individualize how they manage ACE inhibitors and ARBs when patients who have been receiving these drugs long term undergo surgery. However, differing outcomes in observational studies and randomized controlled trials have led to inconsistent guidelines from major cardiovascular societies. This review examines the latest research and guidelines and provides practical recommendations on this topic.

THESE DRUGS NOT ONLY LOWER BLOOD PRESSURE…

ACE inhibitors and ARBs are effective first-line antihypertensive agents and are generally well tolerated.3 They not only lower blood pressure but also mitigate renal disease, reduce the risk of heart failure, and prevent volume overload. Thus, in addition to hypertension, they are indicated to treat heart failure and chronic kidney disease. They are preferred antihypertensive agents in patients with diabetes, too, as they lower the risk of diabetic nephropathy and cardiovascular disease.3,4

ACE inhibitors, as their name indicates, inhibit ACE, thereby preventing conversion of angiotensin I to its vasoconstrictive form, angiotensin II, resulting in vasodilation and reduced vascular resistance. ACE inhibitors also prevent secretion of aldosterone, promoting natriuresis and diuresis and lowering blood pressure (Figure 1).5 However, they raise bradykinin levels, which enhances vasodilation but can also cause side effects such as cough and angioedema.

The renin-angiotensin-aldosterone cascade and drugs that inhibit it. Reprinted from Momoniat T, Ilyas D, Bhandari S. ACE inhibitors and ARBs: managing potassium and renal function. Cleve Clin J Med 2019; 86(9): 601–607. doi:10.3949/ccjm.86a.18024
Figure 1

The renin-angiotensin-aldosterone cascade and drugs that inhibit it.

Reprinted from Momoniat T, Ilyas D, Bhandari S. ACE inhibitors and ARBs: managing potassium and renal function. Cleve Clin J Med 2019; 86(9): 601–607. doi:10.3949/ccjm.86a.18024

ARBs. Angiotensin II acts primarily by binding the angiotensin II type 1 receptor (AT1R).6 ARBs prevent angiotensin II from interacting with the AT1R, which stops its vasoconstrictive and aldosterone-stimulating actions.6

Other drugs inhibit different steps in the reninangiotensin-aldosterone cascade, but because they are used less often than ACE inhibitors and ARBs, we have less information about how to manage their use perioperatively.2

Aliskiren, a direct renin inhibitor, has a long half-life and strong effect on the renin-angiotensin-aldosterone system, in theory creating risks of perioperative hypotension and hyperkalemia that require careful attention when treating patients who have preexisting renal impairment or who are undergoing major surgery.

Sacubitril-valsartan. The valsartan component of this combination is an ARB, while the sacubitril component increases natriuretic peptides by blocking neprilysin, which may lead to vasodilatory hypotension. No research exists about perioperative management of this preparation, but expert consensus and society guidelines say to individualize treatment decisions, temporarily stopping the drug in high-risk cases and promptly resuming it when feasible.

They also protect the kidneys…

ACE inhibitors and ARBs lower blood pressure and reduce proteinuria, but soon after they are started the serum creatinine level rises and the glomerular filtration rate dips. This effect may actually help protect the kidneys in patients with chronic kidney disease, as it is a result of efferent arteriolar vasodilation and a fall in intraglomerular pressure, which reduces renal hyperfiltration and protects the glomerular endothelium. However, a rise in serum creatinine concentration of 30% or more after starting an ACE inhibitor or ARB is worrisome and may prompt discontinuing therapy.5,7–9

…and the heart

Renin-angiotensin-aldosterone system inhibitors enhance cardiac performance by reducing ventricular remodeling and fibrosis, which decreases the likelihood of heart failure progression and cardiovascular death. The most significant cardiac advantages for patients with heart failure stem from enhanced cardiac output together with reduced afterload.

Patients with heart failure are less likely to die or need to be hospitalized if they receive ACE inhibitors (or ARBs if they cannot tolerate ACE inhibitors), and these drugs are established treatments for heart failure.10 In hypertensive patients at cardiovascular risk, they reduce the long-term risks of myocardial infarction and stroke by lowering the blood pressure and stabilizing arterial plaque. Therefore, patients receiving these drugs long term for cardiac indications might fare better if they are continued perioperatively, so as not to precipitate decompensation.

BUT THEY HAVE RISKS

Hypotension is the primary risk associated with these drugs. By blunting angiotensin II–mediated vasoconstriction, they can lower blood pressure too much, particularly in volume-depleted or elderly patients. The combination of chronic renin-angiotensin-aldosterone system blockade and general anesthesia can result in profound and refractory hypotension. For example, Ling et al11 found that patients taking an ACE inhibitor or ARB long term experienced more frequent and severe intraoperative hypotensive episodes.

Acute kidney injury. Perioperative ACE inhibitor and ARB use that leads to hypotension may precipitate acute kidney injury. Arora et al12 reported that intraoperative hypotension is strongly associated with acute kidney injury after cardiac surgery (and so are ACE inhibitors and ARBs). Similarly, a 2024 meta-analysis13 of noncardiac surgeries found that patients whose ACE inhibitors and ARBs were withheld had a significantly lower incidence of postoperative acute kidney injury compared with those who continued them.

The concern for precipitating renal injury led to the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guideline14 recommendation to consider holding renin-angiotensin-aldosterone system inhibitors in the 48 to 72 hours before elective surgery in patients with chronic kidney disease, while recognizing the risk of delayed resumption of therapy.

Hyperkalemia. Chronic ACE inhibitor or ARB therapy suppresses aldosterone, leading to decreased potassium excretion. Patients with normal kidney function have an incidence of hyperkalemia of about 2% when they take these drugs, but those with underlying chronic kidney disease or other circumstances (eg, higher baseline potassium level, diuretic use, diabetes) can be at much greater risk.15 Perioperatively, factors such as acute kidney injury, tissue trauma, or transfusions may further elevate potassium.5

Angioedema, induced by bradykinin, is uncommon but potentially life-threatening when it threatens to close off the airway.

RETROSPECTIVE STUDIES

After multiple cases of refractory intraoperative hypotension were reported, larger cohort studies looked at this association.

Kheterpal et al,16 in a propensity-matched analysis of 12,381 patients undergoing noncardiac surgery, found that those taking ACE inhibitors or ARBs experienced more hypotension and received more vasopressor treatment than those not taking these drugs. However, rates of myocardial infarction and renal failure did not differ between the groups.

The VISION study (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation)17 was a large international cohort study that analyzed major complications after noncardiac surgery, including myocardial injury. In a secondary analysis of the VISION study cohort, 1,245 patients whose ACE inhibitors or ARBs were withheld for 24 hours were compared with 3,557 patients who continued on these drugs.18 Patients whose drugs were stopped before surgery were less likely to die or experience myocardial injury or stroke (adjusted relative risk 0.82) and were also less likely to have intraoperative hypotension (adjusted relative risk 0.80).

Veterans Affairs study. However, holding these drugs around the time of surgery is not entirely benign. A large observational study involving almost 250,000 patients in the US Veterans Affairs healthcare system found that a surprising 25% of those whose chronic ACE inhibitor therapy was stopped had not restarted it within 14 days of surgery.19 Moreover, failure to restart ACE inhibitors was associated with a significantly higher 30-day mortality rate (hazard ratio 3.44).

The same was true with ARBs. In an analysis in the same healthcare system, ARBs were not restarted within 48 hours of surgery in one-third of patients on chronic ARB therapy, and not resuming these medications was also associated with higher postoperative mortality (hazard ratio 1.47).20

PROSPECTIVE TRIALS

Several randomized trials compared a strategy of continuing vs discontinuing ACE inhibitors and ARBs before noncardiac surgery (Table 1).21–24

View this table:
TABLE 1

Randomized trials of withholding vs continuing ACE inhibitors and ARBs before noncardiac surgery

PREOP-ACEI (Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition),21 published in 2018, randomized 275 patients on long-term ACE inhibitor therapy to skip or receive their final preoperative dose. Of note, patients with left ventricular dysfunction or symptomatic heart failure were excluded. Fewer patients whose ACE inhibitor was withheld had intraoperative hypotension (55% vs 69%) or postoperative hypotension, but they had more hypertensive events.

POISE-3 (the third Perioperative Ischemic Evaluation trial),22 in one of its factorial arms, randomized patients to either a “hypotension avoidance” or a “hypertension avoidance” strategy. As in PREOP-ACEI, patients with significant heart failure were excluded. In the hypotension-avoidance group, ACE inhibitors, ARBs, and direct renin inhibitors were withheld (among other somewhat complicated interventions) starting the night before surgery until day 3 after surgery, and clinicians were asked to maintain a higher blood pressure during surgery. In the hypertension-avoidance group, all antihypertensive agents were continued and the intraoperative blood pressure goal was lower.

No difference was detected in the incidence of the primary outcome of major vascular complications (death, myocardial injury after noncardiac surgery, stroke, or cardiac arrest). However, study protocol adherence was “suboptimal.”

The SPACE trial (Stopping Perioperative ACE-Inhibitors or Angiotensin-II Receptor Blockers)23 randomized 262 patients on ACE inhibitors or ARBs undergoing elective noncardiac surgery lasting more than 2 hours to either continue receiving these agents or not for 24 to 48 hours based on the specific drug half-life. Unlike in PREOP-ACEI and POISE-3, patients with left ventricular dysfunction were included. The incidence of myocardial injury or hypotensive episodes requiring treatment did not differ between the groups, but the group that had their ACE inhibitors or ARBs held had more hypertensive episodes.

The Stop-or-Not trial,24 which was much larger, randomized 2,222 patients on chronic ACE inhibitor or ARB treatment undergoing major noncardiac surgery to continue or discontinue these drugs 48 hours before surgery. In view of the retrospective data suggesting that many patients never restart this treatment, the protocol called for resuming this therapy as soon as feasible.

The groups did not differ in the rate of the primary composite outcome of death or major complications. Although the continuation group had a higher rate of hypotensive episodes (54% vs 41%), the average mean difference in hypotensive time per case was only 3.4 minutes, a duration unlikely to be clinically significant.

META-ANALYSES

Ling et al,11 in 2018, conducted a systematic review and meta-analysis of 13 studies of patients on ACE inhibitors or ARBs undergoing noncardiac surgery and found that hypotension during anesthesia was more likely in the continuation group (relative risk 1.41, 95% confidence interval [CI] 1.21–1.64). However, they found no differences in the rates of myocardial infarction, myocardial injury after noncardiac surgery, stroke, major adverse cardiac events, acute kidney injury, or death (relative risk 1.25, 95% CI 0.76–2.04) regardless of subgroup or sensitivity analyses.

Ahmed et al,13 in 2024, performed a meta-analysis of 16 studies (including the POISE-3,22 SPACE,23 and Stop-or-Not24 trials) that included 59,105 patients. They found that withholding ACE inhibitors and ARBs was associated with significantly lower incidences of intraoperative hypotension and acute kidney injury and a significantly higher incidence of postoperative hypertension (odds ratio 1.65, 95% CI 1.16–2.34), but no statistically significant difference in mortality, major adverse cardiac events, myocardial infarction, myocardial injury, or stroke.

CONFLICTING GUIDELINES

Before 2024, different guidelines provided conflicting recommendations regarding renin-angiotensin-aldosterone system inhibitor use in the perioperative period.

The European Society of Cardiology’s 2022 guidelines,25 on the one hand, said withholding these drugs in hypertensive patients and patients without heart failure undergoing noncardiac surgery “should be considered,” in view of concerns about hypotension.

The Canadian Cardiovascular Society’s 2017 guidelines26 similarly recommended stopping them on the day of surgery to avoid hypotension.

The Society for Perioperative Assessment and Quality Improvement, in a consensus statement published in 2022,27 recommended holding ACE inhibitors and ARBs on the day of surgery but considering continuing them if the procedure is low risk.

The 2014 American College of Cardiology and American Heart Association (ACC/AHA) guidelines,28 in contrast, suggested that it was reasonable to continue renin-angiotensin-aldosterone system inhibitor therapy in patients with heart failure, emphasizing cardiovascular stability rather than hypotension risk.

However, these recommendations were based on observational data, not randomized controlled trials, leading to inconsistent clinical practices.

The 2024 ACC/AHA guideline2 incorporated data from some of the randomized controlled trials and meta-analyses discussed above. However, the Stop-or-Not trial24 had not been completed at the time of publication. Nonetheless, the 2024 guideline states that for select patients undergoing high-risk procedures, holding renin-angiotensin-aldosterone system inhibitors may be helpful to minimize hypotension, but that continuing them is reasonable in patients with heart failure. Specifically, the guideline recommends the following2:

  • In patients with controlled blood pressure on chronic renin-angiotensin-aldosterone system inhibitors for hypertension who will undergo elevated-risk noncardiac surgery, stopping the drugs 24 hours before surgery may be beneficial to limit intraoperative hypotension (weak recommendation, moderate-quality evidence)

  • In patients on long-term renin-angiotensin-aldosterone system inhibitors for heart failure with reduced ejection fraction, continuing these drugs perioperatively is reasonable (moderate recommendation, consensus opinion of experts based on clinical experience).

The 2024 KDIGO clinical practice guideline for chronic kidney disease14 also further supports a cautious approach, including a specific practice point recommending the planned discontinuation of ACE inhibitors and ARBs (and sodium-glucose cotransporter 2 inhibitors) before elective surgery. The rationale is to reduce the risk of perioperative complications such as acute kidney injury, hypotension, metabolic acidosis, and hyperkalemia. The KDIGO guideline also emphasizes the importance of resuming these agents postoperatively, particularly in patients with heart failure or proteinuric kidney disease.

As such, judicious withholding of renin-angiotensin-aldosterone system inhibitors in vulnerable populations—and promptly resuming them—may strike the safest balance between renal protection and hemodynamic stability.2

A ROLE FOR CLINICAL ACUMEN

Have we been worrying too much about intraoperative hypotension? Since episodes of hypotension are generally well managed with intraoperative measures, the need to withhold ACE inhibitors and ARBs remains a subject of debate.

Beattie29 points out that although continuing these drugs has been associated with hypotension, high-quality evidence shows that it does not lead to an increase in postoperative cardiovascular events. This perspective raises the question of whether a blanket recommendation to discontinue these drugs before surgery is appropriate or whether a more patient-specific approach should be adopted.

Beattie29 also notes that, to date, 8 randomized trials have examined interventions aimed at reducing the negative effects of perioperative hypotension. These interventions included notification of hypotension, use of artificial intelligence algorithms, modulating intraoperative pressures with inotropes, and preoperative withdrawal of a potential hypotensive medication (eg, ACE inhibitors and ARBs), and none of them was found to be superior to standard anesthesiologist practices.22,23,30–35

In light of emerging research, the tide is turning toward continuing ACE inhibitors and ARBs during noncardiac surgery. For instance, Legrand,36 in an editorial, hypothesizes that the increase in myocardial injury after noncardiac surgery seen in patients with low preoperative N-terminal pro–brain natriuretic peptide (NT-proBNP) levels may be due to these patients having higher angiotensin II concentrations, leading to a more pronounced arterial rebound when treatment is withheld. Sudden increases in blood pressure can contribute to myocardial injury.

Factors to consider

In view of the varying society guidelines, clinicians must still weigh several factors when deciding how to manage ACE inhibitors and ARBs in the perioperative setting:

The patient’s baseline cardiovascular status, vital signs, and blood pressure regimen must be considered.

Whether the patient has heart failure or chronic kidney disease. It is critically important for a patient with a low ejection fraction or chronic kidney disease to continue their therapy, whereas patients with well-controlled hypertension and preserved ejection fraction may tolerate withholding these drugs.

The inherent risk of surgery. The potential for significant blood loss or extended surgical periods with little stimulation may justify stopping renin-angiotensin-aldosterone system inhibitors to reduce the risk of hypotension during operations. For low-risk surgical procedures that generate minimal hemodynamic changes, continuing this treatment generally presents no substantial risk.

Hospital protocols. Many hospitals have established standardized medication instruction protocols, influencing decisions about ACE inhibitors and ARBs. Preoperative clinics have different staffing models, and many different caregivers may give medication instructions. Instructions are safest when a rubric is followed. In institutions with a proactive hemodynamic management strategy, continuation of these drugs may be feasible with appropriate monitoring and intervention measures in place.

Biomarker levels. The latest ACC/AHA guideline highlights the potential role of NT-proBNP levels in identifying patients who would benefit from discontinuing ACE inhibitors and ARBs vs those at higher risk for myocardial injury if they discontinue treatment. Implementing biomarker-guided strategies may enhance individualized patient care and optimize perioperative outcomes.2

Type of anesthesia. Patients undergoing regional anesthesia techniques, such as upper-extremity plexus blocks for shoulder surgeries, may experience predictable periods of hypotension before surgery. In such cases, withholding ACE inhibitors and ARBs may be warranted to minimize intraoperative blood pressure fluctuations.

WAITING FOR CLARITY

Because of the potential risks associated with withholding ACE inhibitors and ARBs, along with emerging evidence suggesting no significant harm from their continuation, current cardiovascular society recommendations increasingly support maintaining these medications.2

Upcoming large-scale randomized controlled trials will eventually bring clarity, but clinicians should currently steer through the perioperative medicine developments using evidence-based methods. Gathering available data, including the indication for the drug, will be beneficial in preoperative medication management. Optimal perioperative care depends on assessing cardiovascular status alongside surgical risks and institutional practices while incorporating biomarker data, when appropriate, and patient-focused approaches.

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

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Cleveland Clinic Journal of Medicine

Cleveland Clinic Journal of Medicine

Vol. 92, Issue 10

1 Oct 2025

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    Hold ACE inhibitors and ARBs before noncardiac surgery? Emerging evidence suggests a patient-specific approach
    • Cleveland Clinic Journal of Medicine
    • October 2025,
    • 92
    • (10)
    • 619-626;
    • DOI: 10.3949/ccjm.92a.25035

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Cardiology
Hospital Medicine
Nephrology