LANdiolol to Avoid TAchycardia in Patients at Risk for Cardiovascular Events Undergoing Major Non-cardiac Surgery (LANTA-P)

Insel Gruppe AG, University Hospital Bern

Status and phase: Not yet enrolling; Phase 4

Conditions: Myocardial Injury After Non-cardiac Surgery; Cardiovascular (CV) Risk; Beta Blocker; Major Surgery; Perioperative Myocardial Injury; Autonomic Dysfunction

Treatments: Drug: Landiolol

Study type: Interventional

Funder types: Other

Identifiers

NCT07168421

BECD-1-21

Details and patient eligibility

About

Limiting perioperative tachycardia (aiming for a heart rate <90 beats per minute throughout the perioperative period) using the ultra-short acting beta-blocker landiolol in patients with cardiovascular risk factors undergoing major surgery might lower the incidence of perioperative myocardial injury. Feasibility of the intervention needs to be proven prior to conduction of a larger trial.

Full description

Despite advances in surgical and anaesthetic techniques, perioperative mortality remains high, even in developed countries. Major complications contributing almost half of all deaths after surgery are major bleeding (17%), myocardial injury after non-cardiac surgery (13%) and sepsis (12%). Myocardial injury after non-cardiac surgery occurs up to 18% in patients >45 years and is associated with a marked increase in 30-day mortality. Additional factors posing patients at risk for perioperative myocardial injury might be autonomic dysfunction, measured as exaggerated heart rate response to exercise or impaired heart rate recovery thereafter, as perioperative tachycardia is associated with perioperative myocaridal injury. The perioperative use of beta-blockers remains controversial, but the newely marketed ultra-short acting and highly cardioselective beta-blocker landiolol offers the opportunity to reduce perioperative heart rate without affecting blood pressure. The intervention (perioperative reduction of heart rate using landiolol) in this specific patient population needs to be proven as feasible prior to conducting a larger scale trial.

Enrollment: 114 estimated patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients undergoing elective non-cardiac surgery defined as intermediate or high-risk by the 2022 european society of cardiology (ESC) guidelines

• expected duration of surgery of at least 90 minutes;

• expected length of hospital stay ≥ 24 hours;

• age > 45 years with at least two of the following risk factors (adapted from revised cardiac risk index):

  • 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;
  • insulin-dependent diabetes mellitus;
  • creatinine > 176.8 mmol/l;
  • pre-operative NTproBNP > 200 pg/ml;

• excessive sympathetic outflow as proven by exercise testing:

  • impaired HR recovery (≤ 12 bpm within 1 minute after cessation of exercise); OR
  • exaggerated HR response (≥ 12 bpm after 1 minute 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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114 participants in 2 patient groups

Landiolol

Experimental group

Description:

Landiolol will be titrated to keep heart rate below 90 beats per minute during surgery after exclusion of other factors possibly causing tachycardia (such as hypovolaemia or pain). Mean arterial pressure will be kept above 65 millimeters of mercury.

Treatment:

Drug: Landiolol

Usual care

No Intervention group

Description:

In the usual care group, mean arterial pressure will be maintained above 65 millimeters of mercury. In case of tachycardia, causing reasons (such as hypovolaemia) will be sought and treated.