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The cardiac MRI substudy to ongoing telmisartan alone and in combination with ramipril global endpoint trial/telmisartan randomized assessment study in ACE-intolerant subjects with cardiovascular disease: analysis protocol and baseline characteristics

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Abstract

Background

The ONTARGET and TRANSCEND clinical trials were designed to investigate the cardioprotective effects of telmisartan 80 mg and ramipril 10 mg, alone and in combination, in patients at high risk of cardiovascular disease. Cardiac MRI enables investigation of mechanistic effects of these agents on cardiac structural and functional variables. Here, we report the design, analysis protocol, reproducibility and relevant quality control procedures, and baseline patient characteristics of the ONTARGET/TRANSCEND cardiac MRI substudy. MRI was undertaken in 330 subjects enrolled in ONTARGET, and 38 subjects in TRANSCEND, across eight centers in six countries. Analyses were performed by two independent analysts using guide-point modeling. Cases with discrepancies in LV mass (LVM) of >5% were independently reanalyzed. Cases with discrepancies in end-diastolic volume (EDV) of >5%, or end-systolic volume (ESV) of >12%, were then reconciled by consensus.

Results

Baseline characteristics were broadly similar to the main ONTARGET/TRANSCEND trials, except for a higher frequency of coronary artery disease and Asian ethnicity in the substudy. Reproducibility of MRI analyses (mean ± SD) were 2.8 ± 3.7 ml in EDV, −0.3 ± 3.6 ml in ESV, 3.1 ± 3.3 ml in SV, 1.1 ± 1.8% in EF, and 0.4 ± 4.5 g in LVM. Subgroup analyses revealed increased ESV and LVM, and reduced EF, in subjects with a history of either coronary artery disease or myocardial infarction.

Conclusions

The ONTARGET/TRANSCEND cardiac MRI substudy protocol provides for a reliable assessment of the effects of telmisartan and ramipril, alone and in combination, on cardiac structural and functional parameters over a 2-year follow-up period.

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Acknowledgments

The authors thank Dr RA Stewart, Green Lane Cardiovascular Service, Auckland, New Zealand, for the inclusion of the scan-rescan reproducibility data.

Author information

Authors and Affiliations

  1. Auckland MRI Research Group, University of Auckland, Auckland, New Zealand

    Brett R. Cowan & Alistair A. Young

  2. Clinical Trials Research Unit, School of Population Health, University of Auckland, Auckland, New Zealand

    Craig Anderson & Angela K. Wadham

  3. The George Institute For International Health, University of Sydney and Royal Prince Alfred Hospital, Sydney, Australia

    Craig Anderson

  4. Department of Medicine, University of Auckland, Auckland, New Zealand

    Robert N. Doughty

  5. Division of Cardiology, Department of Medicine, Siriraj Hospital, Bangkok, Thailand

    Rungroj Krittayaphong

  6. Department of Medicine, Division of Cardiology and Population Health Research Institute, McMaster University, Hamilton, ON, Canada

    Eva Lonn, Koon Teo & Salim Yusuf

  7. Department of Medicine, University of Queensland, Brisbane, Australia

    Thomas H. Marwick

  8. Department of Cardiovascular Medicine, University of Birmingham, Birmingham, UK

    John E. Sanderson

  9. Department of Nephrology and Hypertension, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany

    Roland E. Schmieder

  10. Baker IDI Heart and Diabetes Institute, Melbourne, Australia

    Chris M. Reid & Garry L. Jennings

  11. CCRE Therapeutics, Monash University, Melbourne, Australia

    Chris M. Reid

  12. Cardiovascular Investigation Unit, Royal Adelaide Hospital, Adelaide, Australia

    Stephen G. Worthley

  13. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong

    Cheuk-Man Yu

  14. Department of Anatomy with Radiology, The University of Auckland, 85 Park Ave, Grafton, Auckland, New Zealand

    Alistair A. Young

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  1. Brett R. Cowan
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Correspondence to Alistair A. Young.

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Cowan, B.R., Young, A.A., Anderson, C. et al. The cardiac MRI substudy to ongoing telmisartan alone and in combination with ramipril global endpoint trial/telmisartan randomized assessment study in ACE-intolerant subjects with cardiovascular disease: analysis protocol and baseline characteristics. Clin Res Cardiol 98, 421–433 (2009). https://doi.org/10.1007/s00392-009-0014-4

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  • DOI: https://doi.org/10.1007/s00392-009-0014-4

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