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J Am Heart Assoc. 2016 Mar 9;5(3):e002708. doi: 10.1161/JAHA.115.002708.

Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index, Infarct Size, or Biochemical Markers as Endpoint.

Author information

1
Department of Clinical Sciences Lund, Clinical Physiology, Skane University Hospital, Lund University, Lund, Sweden.
2
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.
3
Department of Cardiology, Skåne University Hospital and Lund University, Lund, Sweden.
4
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
5
Department of Clinical Science, University of Bergen, Norway.
6
Department of Cardiology, Henri Mondor Hospital, Creteil, France.
7
Department of Cardiology B, Oslo University Hospital Ullevål, University of Oslo, Norway Faculty of Medicine, University of Oslo, Norway.
8
Section for Interventional Cardiology, Department of Cardiology, Oslo University Hospital, Ullevål, Norway.
9
Department of Clinical Sciences Lund, Clinical Physiology, Skane University Hospital, Lund University, Lund, Sweden hakan.arheden@med.lu.se.

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.

METHODS AND 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%.

CONCLUSION:

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.

KEYWORDS:

acute myocardial infarction; biochemical markers; cardioprotection; myocardial salvage index; sample size

PMID:
26961520
PMCID:
PMC4943247
DOI:
10.1161/JAHA.115.002708
[Indexed for MEDLINE]
Free PMC Article

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