Holding angiotensin-axis blockers before elective surgery gave no benefit in a randomised trial

Design

Single-centre, single-blind randomised controlled trial, 1:1 allocation

Population

638 analysed adults on stable angiotensin-axis blockade for ≥28 days before elective non-cardiac surgery; mean age 66

Primary outcome

Composite of major adverse cardiovascular events at 5 days

Effect

2.8% continuing vs 2.9% withholding; difference 0.1% (95% CI −2.5% to 2.8%), p = 1.00

Guidelines have favoured withholding angiotensin-converting enzyme inhibitors and angiotensin receptor blockers before elective non-cardiac surgery in patients without hypertension or systolic heart failure, on the reasoning that they contribute to intraoperative hypotension and cardiorenal injury. The trial evidence for that reasoning has been thin.

Patients attending a preoperative clinic on a stable dose for at least 28 days were randomised 1:1 either to continue or to withhold the drug for 24 hours before surgery. After 29 post-randomisation exclusions, 325 continuing and 313 withholding were analysed. The primary composite of major adverse cardiovascular events at five days occurred in 2.8% and 2.9% — a difference of 0.1% with a confidence interval from −2.5% to 2.8%.

The secondary outcomes point the same way. Intraoperative hypotension occurred in 63.5% of those continuing and 60.7% of those withholding, and acute kidney injury in 7.4% and 4.8%, neither difference significant. No subgroup behaved differently. The most striking number is not the comparison at all: intraoperative hypotension affected more than 60% of patients in both arms, so whatever is causing it is largely not the angiotensin-axis blocker.

• In a low-risk patient for elective non-cardiac surgery, continuing the drug is defensible on this evidence
• The trial withheld for 24 hours — it does not address longer preoperative holds
• Stopping and not restarting is its own harm; if you hold, write the restart date
• Intraoperative hypotension was the norm in both arms, so anaesthetic technique and fasting are the larger levers
• This population was low cardiac risk; it does not speak to patients with systolic heart failure

Why it matters

It removes the evidential basis for a widespread preoperative instruction, and every unnecessary hold is a chance for the drug never to be restarted.

Don't overread it

Single centre, single blind, and powered for a composite that occurred in fewer than 3% of patients. A confidence interval from −2.5% to 2.8% is compatible with a small benefit either way; this is absence of evidence of difference, not proof of equivalence.

The statistics, in plain English

With only 18 primary events across 638 patients, the trial can exclude a large difference but not a modest one — the interval spans roughly 2.5 percentage points in both directions. That is still informative, because the guideline advice it tests assumes a benefit large enough to justify routine withholding, and a benefit that size would have shown. Read it as removing the justification for the instruction rather than as establishing that the two strategies are identical.

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