Landiolol to prevent fast heart rates during major non-cardiac surgery in patients with cardiovascular risk

LANdiolol to Avoid TAchycardia in Patients at Risk for Cardiovascular Events Undergoing Major Non-cardiac Surgery: a Feasibility Trial

This will test whether giving the ultra‑short acting beta‑blocker landiolol to people over 45 with cardiovascular risk factors who are having major non‑cardiac surgery can keep heart rate below 90 bpm throughout the perioperative period and reduce heart injury.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 114 (estimated)
• Ages: 45 Years and up
• Sex: All
• Sponsor: Insel Gruppe AG, University Hospital Bern (Academic / other)
• Locations: 1 site (Bern)
• Trial ID: NCT07168421 on ClinicalTrials.gov

What this trial studies

This Phase 4 intervention uses continuous perioperative administration of the highly cardioselective, ultra‑short acting beta‑blocker landiolol to limit tachycardia (target heart rate <90 bpm) in patients at cardiovascular risk undergoing elective intermediate‑ or high‑risk non‑cardiac surgery under general anesthesia. Eligible participants are adults ≥45 years with at least two cardiovascular risk factors and evidence of excessive sympathetic outflow on exercise testing (impaired heart rate recovery or exaggerated heart rate response). The primary goal is to demonstrate feasibility of maintaining the heart rate target without causing hypotension or other safety issues, as a precursor to a larger efficacy trial measuring perioperative myocardial injury. The intervention is delivered perioperatively at Bern University Hospital with close hemodynamic monitoring.

Who should consider this trial

Good fit: Ideal candidates are adults aged 45 or older scheduled for elective intermediate‑ or high‑risk non‑cardiac surgery under general anesthesia, expected to stay ≥24 hours, who have at least two cardiovascular risk factors and abnormal exercise testing showing excessive sympathetic response.

Not a fit: Patients having low‑risk or minor procedures, those without multiple cardiovascular risk factors or without signs of autonomic dysfunction, and those with contraindications to beta‑blockers (for example severe bradycardia, high‑degree AV block, or active bronchospasm) are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could reduce the incidence of perioperative myocardial injury by preventing excessive tachycardia while avoiding blood pressure compromise.

How similar studies have performed: Prior trials of perioperative beta‑blockade have shown mixed results, and the use of ultra‑short acting, highly cardioselective landiolol is relatively new with limited but promising feasibility and safety data.

Eligibility criteria

Inclusion Criteria:

* Patients undergoing elective non-cardiac surgery defined as intermediate or high-risk by the 2022 european society of cardiology (ESC) guidelines
* surgery performed under general anesthesia;
* expected length of hospital stay ≥ 24 hours;
* age ≥ 45 years;
* at least two of the following risk factors:

  * age ≥ 75 years
  * arterial hypertension;
  * ischemic heart disease (history of myocardial infarction or positive exercise test, current complaint of chest pain considered to be secondary to myocardial ischemia, use of nitrates, pathological Q waves, prior coronary revascularization);
  * history of congestive heart failure;
  * history of cerebrovascular disease;
  * peripheral artery disease;
  * diabetes mellitus;
  * GFR ≤ 59 ml/min pro 1.73 m2;
  * pre-operative NTproBNP \> 200 pg/ml;
* excessive sympathetic outflow as proven by exercise testing:

  * impaired heart rate recovery (≤ 12 bpm within 1 minute after cessation of exercise); OR
  * exaggerated heart rate response (≥ 12 bpm after 3 minutes of unloaded pedalling);

Exclusion Criteria:

* unable to consent or follow study procedures;
* absolute contraindications for exercise testing;
* pregnancy or intention to become pregnant;
* active cardiac conditions (such as unstable coronary syndromes, decompensated heart failure, significant arrhythmias, severe valvular disease);
* urgent / emergency surgery;
* already on β-blocker (within the last 30 days prior to recruitment);
* contraindication for β-blocker therapy (bradycardia (HR \< 55 bpm), hypotension (systolic blood pressure \< 100 mmHg), severe peripheral vascular disease, severe asthma, allergy, higher-degree atrioventricular block);
* severe preoperative anaemia (haemoglobin \< 100 g/L) unless there is a plan set up and followed for correction prior to surgery;
* planned intermediate care or intensive care admission;
* prior enrolment in this trial.

Where this trial is running

Bern

• Bern University Hospital, Freiburgstrasse — Bern, Switzerland (Recruiting)

Study contacts

• Study coordinator: Christian M Beilstein, MD

Conditions Perioperative Myocardial Injury; Autonomic Dysfunction; Cardiovascular Risk; Major Surgery; Beta Blocker; Myocardial Injury After Non-cardiac Surgery; perioperative myocardial injury; major surgery