Ivabradine in Patients Undergoing Noncardiac Surgery: A Randomized Controlled Trial
Abstract
BACKGROUND: Perioperative beta blockade lowers heart rate and decreases the risk of myocardial infarction but increases the risk of hypotension, death, and stroke. Ivabradine, a selective heart rate–lowering agent, may prevent prognostically important myocardial injury after noncardiac surgery (MINS) without causing hemodynamic instability. METHODS: In this multicenter, double-blind, placebo-controlled trial, we assigned patients ≥45 years of age with, or at risk of, atherosclerotic disease undergoing noncardiac surgery to receive ivabradine (5 mg orally twice daily for up to 7 days, starting 1 hour before surgery) or placebo. The primary outcome was MINS within 30 days from randomization. RESULTS: All of the 2101 participants who underwent randomization were included in the intention-to-treat population. MINS occurred in 178 of 1050 patients (17.0%) in the ivabradine group and in 159 of 1051 patients (15.1%) in the placebo group (relative risk, 1.12 [95% CI, 0.92 to 1.37]; P =0.25). Enrollment was halted at the prespecified interim analysis because of a conditional power of 6%, below the futility boundary of 20%. The intraoperative mean heart rate was lower in the ivabradine group by 3.2 beats per minute than in the placebo group (95% CI, –4.07 to –2.36), with no difference in intraoperative mean arterial pressure. CONCLUSIONS: Among patients undergoing noncardiac surgery, ivabradine did not reduce the occurrence of MINS. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05279651.
Article Details
Authors (115)
Jakub Fronczek
Centre for Intensive Care and Perioperative Medicine (W.S., J.F., Z.P., A. Włudarczyk, J.G., B.S.), Jagiellonian University Medical College, Krakow, Poland.
Bożena Seczyńska
Centre for Intensive Care and Perioperative Medicine (W.S., J.F., Z.P., A. Włudarczyk, J.G., B.S.), Jagiellonian University Medical College, Krakow, Poland.
Dominika Gryszówka
Jagiellonian Center for Clinical Trials (D.G., A. Widawska), Jagiellonian University Medical College, Krakow, Poland.
Agnieszka Widawska
Jagiellonian Center for Clinical Trials (D.G., A. Widawska), Jagiellonian University Medical College, Krakow, Poland.
Zhiguo Zhao
Yu Shyr
Department of Biostatistics, Vanderbilt University Medical Center
P.J. Devereaux
Population Health Research Institute, McMaster University, Hamilton, ON, Canada
Szymon Białka
Department of Anesthesiology and Intensive Care, Faculty of Medical Sciences in Zabrze (S.B., P.P.), Medical University of Silesia, Katowice, Poland.
Piotr Palaczyński
Department of Anesthesiology and Intensive Care, Faculty of Medical Sciences in Zabrze (S.B., P.P.), Medical University of Silesia, Katowice, Poland.
Justyna Danel
Mateusz Rydel
Tomasz Gorzkowicz
Maja Copik
Paweł Kutnik
Faculty of Medicine, Institute of Medical Sciences, John Paul II Catholic University of Lublin, Poland (M.B., P.K.).
Michał Borys
Faculty of Medicine, Institute of Medical Sciences, John Paul II Catholic University of Lublin, Poland (M.B., P.K.).
Paweł Piwowarczyk
Marta Łukasik
Katarzyna Kosz
Justyna Sysiak-Sławecka
Marzena Kotus
Wojciech Szczeklik
Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland (W.S., Z.P.).
Anna Włudarczyk
Centre for Intensive Care and Perioperative Medicine (W.S., J.F., Z.P., A. Włudarczyk, J.G., B.S.), Jagiellonian University Medical College, Krakow, Poland.
Jacek Górka
Centre for Intensive Care and Perioperative Medicine (W.S., J.F., Z.P., A. Włudarczyk, J.G., B.S.), Jagiellonian University Medical College, Krakow, Poland.
Zbigniew Putowski
Centre for Intensive Care and Perioperative Medicine, Jagiellonian University Medical College, Krakow, Poland (W.S., Z.P.).
Magdalena Żołyniak
Elżbieta Surdek
Marcin Dec
Kamil Cholewa
Maria Szymonowicz
Marta Bombińska
Izabela Pabjanczyk
Alicja Sekulak
Marcelina Czok
Beata Łukasik
Tomasz Czarnik
Department of Anesthesiology and Intensive Care, Institute of Medical Sciences, University of Opole, Poland (T.C.).
Tomasz Królicki
Jakub Jędrzejczyk
Marcin Możański
Department of Anesthesiology and Intensive Care, Military Institute of Medicine-National Research Institute, Warsaw, Poland (M. Możański).
Anna Janus
Weronika Machura
Klaudia Kampa-Lewandowska
Renata Sośnicka
Anna Szczepańska
Department of Anesthesiology and Intensive Care, School of Medicine in Katowice (A.S.), Medical University of Silesia, Katowice, Poland.
Hajder Norbert
Stanisław Wawrzyniak
Szymon Czajka
Dariusz Onichimowski
Marcin Mieszkowski
Department of Anesthesiology and Intensive Care, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland (M. Mieszkowski).
Milena Samiec
Jakub Ruść
Mariusz Kęska
Katarzyna Kotfis
Department of Anesthesiology, Intensive Care and Pain Management (K.K.), Pomeranian Medical University in Szczecin, Poland.
Igor Karolak
Karolina Kaim-Gutowska
Zuzanna Nikodemska
Elżbieta Reszka
Zuzanna Łazor
Janusz Trzebicki
Paweł Wrzesień
Agnieszka Karwacka-Kramarz
Piotr Mieszczański
Agata Skrzyńska
Julia Derdulska
Waldemar Machała
Łukasz Sadowski
Klaudia Łącz
Jan Aszkielaniec
Joanna Sołek-Pastuszka
Department of Anesthesiology and Intensive Therapy (J.S.-P.), Pomeranian Medical University in Szczecin, Poland.
Agata Andrzejewska
Hanna Baran
Bartosz Szostak
Tomasz Przybylski
Jakub Ludwikowski
Paweł Grudzień
Department of Anesthesiology and Intensive Therapy, Specialized Hospital of E. Szczeklik in Tarnów, Poland (P.G.).
Aleksandra Kita
Tomasz Seremet
Joanna Barnaś-Franczak
Wojciech Mudyna
Department of Anesthesiology and Intensive Therapy, Ludwik Rydygier Memorial Specialist Hospital in Krakow, Poland (W.M.).
Krzysztof Węgrzyn
Agnieszka Misiewska-Kaczur
Department of Anesthesiology and Intensive Therapy, Silesian Hospital in Cieszyn, Poland (A.M.-K.).
Przemysław Jasiński
Janusz Dadok
Maciej Kapias
Radosław Owczuk
Anna Dylczyk–Sommer
Mateusz Jerzy Kreczko
Bartosz Kudliński
Magdalena Murkos
Dorota Studzińska
Faculty of Medical Sciences, Academy of Silesia, Katowice, Poland (D.S.).
Maciej Chwała
Joanna Lelek
Klaudia Tomala
Jarosław Pawlik
Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Poland (J.P.).
Marta Jezierska
Katarzyna Hognon-Bąk
Natalia Popek
Adam Makowski
2nd Department of Anesthesiology and Intensive Care (A.M.), Medical University of Warsaw, Poland.
Paweł Koczara
Julia Wojtkiewicz
Mirosław Ziętkiewicz
Department of Anesthesiology and Intensive Care (M.Z.), Jagiellonian University Medical College, Krakow, Poland.
Bartosz Szwagierczak
Jacek Pietrzyk
Maciej Chmielarz
Mikołaj Przydacz
Department of Urology (M.P.), Jagiellonian University Medical College, Krakow, Poland.
Jakub Szymanski
Kamil Tyrak
Waldemar Goździk
Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Poland (W. Goździk).
Marek Wełna
Ewa Woźnica-Niesobska
Wojciech Gola
The Institute of Health Sciences, Department of Nursing, Midwifery and Emergency Medicine, Collegium Medicum, Jan Kochanowski University in Kielce, Poland (W. Gola).
Jacek Milecki
Adam Wółkiewicz
Przemysław Jasiewicz
Department of Anesthesiology and Intensive Care, Nicolaus Copernicus University Ludwik Rydygier Collegium Medicum in Bydgoszcz, Poland (P.J.).
Marcin Schiller
Paweł Jarocki