title: Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index, Infarct Size, or Biochemical Markers as Endpoint.
abstract: BACKGROUND
  Cardiac magnetic resonance (CMR) can quantify myocardial infarct (MI) size and myocardium at risk (MaR), enabling assessment of myocardial salvage index (MSI). We assessed how MSI impacts the number of patients needed to reach statistical power in relation to MI size alone and levels of biochemical markers in clinical cardioprotection trials and how scan day affect sample size.
  
  
  RESULTS
  Controls (n=90) from the recent CHILL-MI and MITOCARE trials were included. MI size, MaR, and MSI were assessed from CMR. High-sensitivity troponin T (hsTnT) and creatine kinase isoenzyme MB (CKMB) levels were assessed in CHILL-MI patients (n=50). Utilizing distribution of these variables, 100 000 clinical trials were simulated for calculation of sample size required to reach sufficient power. For a treatment effect of 25% decrease in outcome variables, 50 patients were required in each arm using MSI compared to 93, 98, 120, 141, and 143 for MI size alone, hsTnT (area under the curve [AUC] and peak), and CKMB (AUC and peak) in order to reach a power of 90%. If average CMR scan day between treatment and control arms differed by 1 day, sample size needs to be increased by 54% (77 vs 50) to avoid scan day bias masking a treatment effect of 25%.
  
  
  CONCLUSIONS
  Sample size in cardioprotection trials can be reduced 46% to 65% without compromising statistical power when using MSI by CMR as an outcome variable instead of MI size alone or biochemical markers. It is essential to ensure lack of bias in scan day between treatment and control arms to avoid compromising statistical power.
authors.affiliation: Department of Clinical Sciences Lund, Clinical Physiology, Skane University Hospital, Lund University, Lund, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Engblom
authors.affiliation: Department of Clinical Sciences Lund, Clinical Physiology, Skane University Hospital, Lund University, Lund, Sweden Department of Biomedical Engineering, Faculty of Engineering, Lund University, Lund, Sweden.
authors.forename: Einar
authors.initials: E
authors.lastname: Heiberg
authors.affiliation: Department of Cardiology, Skåne University Hospital and Lund University, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.affiliation: Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Svend Eggert
authors.initials: SE
authors.lastname: Jensen
authors.affiliation: Department of Clinical Science, University of Bergen, Norway.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Nordrehaug
authors.affiliation: Department of Cardiology, Henri Mondor Hospital, Creteil, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Randé
authors.affiliation: Department of Cardiology B, Oslo University Hospital Ullevål, University of Oslo, Norway Faculty of Medicine, University of Oslo, Norway.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Halvorsen
authors.affiliation: Section for Interventional Cardiology, Department of Cardiology, Oslo University Hospital, Ullevål, Norway.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hoffmann
authors.affiliation: Department of Cardiology, Skåne University Hospital and Lund University, Lund, Sweden.
authors.forename: Sasha
authors.initials: S
authors.lastname: Koul
authors.affiliation: Department of Clinical Sciences Lund, Clinical Physiology, Skane University Hospital, Lund University, Lund, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Carlsson
authors.affiliation: Department of Cardiology B, Oslo University Hospital Ullevål, University of Oslo, Norway Faculty of Medicine, University of Oslo, Norway.
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.affiliation: Department of Clinical Sciences Lund, Clinical Physiology, Skane University Hospital, Lund University, Lund, Sweden hakan.arheden@med.lu.se.
authors.forename: Håkan
authors.initials: H
authors.lastname: Arheden
mesh_terms: D015982:Bias; D015415:Biomarkers / Q000097:blood; D003198:Computer Simulation; D052279:Creatine Kinase, MB Form / Q000097:blood*; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D011237:Predictive Value of Tests; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015203:Reproducibility of Results; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D020107:Troponin T; D052279:Creatine Kinase, MB Form
keywords: acute myocardial infarction; biochemical markers; cardioprotection; myocardial salvage index; sample size