PERIOPERATIVE MEDICINE / ORIGINAL ARTICLE
Association between NT-proBNP and ivabradine in patients after noncardiac surgery: a per-protocol analysis of the PREVENT-MINS study
1
Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland
2
Department of Anesthesiology and Intensive Care, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
3
Faculty of Medicine, Institute of Medical Sciences, The John Paul II Catholic University of Lublin, Poland
4
Department of Anesthesiology and Intensive Care, Institute of Medical Sciences, University of Opole, Poland
5
Department of Anesthesiology and Intensive Care, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
6
Doctoral School, Medical University of Silesia, Katowice, Poland
7
Department of Anesthesiology and Intensive Care, Military Institute of Medicine-National Research Institute, Poland
8
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, University of Warmia and Mazury, Olsztyn, Poland
9
Department of Anesthesiology, Intensive Care and Pain Management, Pomeranian Medical University in Szczecin, Poland
10
Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
11
1st Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Poland
12
Department of Anesthesiology and Intensive Therapy, Central Teaching Hospital of the Medical University of Lodz, Poland
13
Department of Anesthesiology and Intensive Therapy, Pomeranian Medical University in Szczecin, Szczecin, Poland
14
Department of Anesthesiology and Intensive Therapy, Specialized Hospital of E. Szczeklik in Tarnów, Poland
15
Department of Anesthesiology and Intensive Therapy, Ludwik Rydygier Memorial Specialist Hospital in Krakow, Poland
16
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Medical University of Gdansk, Poland
17
Department of Anesthesiology and Intensive Therapy, University Clinical Centre, Gdansk, Poland
18
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, USA
19
Departments of Health Evidence and Impact and Medicine and Population Health Research Institute, McMaster University, and the World Health Research Incorporated, Hamilton, Ontario, Canada
Submission date: 2025-12-17
Acceptance date: 2025-12-29
Publication date: 2025-12-29
Corresponding author
Wojciech Szczeklik
Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland
Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland
Anaesthesiol Intensive Ther 2025;57(1):391-398
KEYWORDS
ivabradinenoncardiac surgeryNT-proBNPmyocardial injuryrandomized controlled trialper-protocol analysis
TOPICS
ABSTRACT
Background:
The PREVENT-MINS trial investigated whether perioperative heart rate reduction with ivabradine could prevent myocardial injury after noncardiac surgery (MINS). Although ivabradine modestly reduced heart rate, it did not reduce the incidence of MINS in the intention-to-treat analysis. This per-protocol analysis of the PREVENT-MINS trial, with a post-hoc biomarker substudy, evaluated whether perioperative ivabradine modifies postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, a marker of perioperative cardiovascular risk.
Methods:
This analysis included 2008 participants who received ≥ 1 dose of study drug, underwent surgery, and had NT-proBNP and troponin measured (ivabradine: n = 1,001; placebo: n = 1,007). Postoperative NT-proBNP levels and changes from baseline (ΔNT-proBNP) were compared by treatment allocation. Clinical outcomes and safety endpoints from the parent trial were evaluated. Analysis of covariance (ANCOVA) assessed ivabradine’s effect on postoperative NT-proBNP after adjustment for baseline values and clinical covariates.
Results:
MINS occurred in 17.7% of ivabradine-treated vs. 15.7% of placebo patients (RR 1.13; 95% CI: 0.93–1.37; P = 0.23). Median postoperative NT-proBNP was higher with ivabradine than with placebo (418.0 vs. 333.5 pg mL–1; P < 0.001), as were ΔNT-proBNP values (215.1 vs. 154.0 pg mL–1; P < 0.001). After adjustment for baseline and relevant clinical covariates, ivabradine was independently associated with an approximately 82% increase in postoperative NT-proBNP (Δlog = 0.59 ± 0.19; 95% CI: 26–164).
Conclusions:
Ivabradine did not reduce the incidence of MINS and was associated with greater postoperative NT-proBNP release. Perioperative heart rate reduction with ivabradine may elevate markers of cardiac stress without measurable clinical benefit.
The PREVENT-MINS trial investigated whether perioperative heart rate reduction with ivabradine could prevent myocardial injury after noncardiac surgery (MINS). Although ivabradine modestly reduced heart rate, it did not reduce the incidence of MINS in the intention-to-treat analysis. This per-protocol analysis of the PREVENT-MINS trial, with a post-hoc biomarker substudy, evaluated whether perioperative ivabradine modifies postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, a marker of perioperative cardiovascular risk.
Methods:
This analysis included 2008 participants who received ≥ 1 dose of study drug, underwent surgery, and had NT-proBNP and troponin measured (ivabradine: n = 1,001; placebo: n = 1,007). Postoperative NT-proBNP levels and changes from baseline (ΔNT-proBNP) were compared by treatment allocation. Clinical outcomes and safety endpoints from the parent trial were evaluated. Analysis of covariance (ANCOVA) assessed ivabradine’s effect on postoperative NT-proBNP after adjustment for baseline values and clinical covariates.
Results:
MINS occurred in 17.7% of ivabradine-treated vs. 15.7% of placebo patients (RR 1.13; 95% CI: 0.93–1.37; P = 0.23). Median postoperative NT-proBNP was higher with ivabradine than with placebo (418.0 vs. 333.5 pg mL–1; P < 0.001), as were ΔNT-proBNP values (215.1 vs. 154.0 pg mL–1; P < 0.001). After adjustment for baseline and relevant clinical covariates, ivabradine was independently associated with an approximately 82% increase in postoperative NT-proBNP (Δlog = 0.59 ± 0.19; 95% CI: 26–164).
Conclusions:
Ivabradine did not reduce the incidence of MINS and was associated with greater postoperative NT-proBNP release. Perioperative heart rate reduction with ivabradine may elevate markers of cardiac stress without measurable clinical benefit.
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| eISSN: | 1731-2531 |
| ISSN: | 1642-5758 |
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