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Heart Failure with Preserved Ejection Fraction Trials Have Heterogeneous Control Groups: a Comparison of Kaplan-Meier Curves

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Abstract

Purpose

Previous studies have evaluated intra-study heterogeneities of heart failure with preserved ejection fraction (HFpEF), but inter-study heterogeneities remain poorly understood. We investigate the heterogeneities of outcomes among control groups of HFpEF trials.

Methods

We included randomized controlled trials recruiting HFpEF patients with ejection fraction ≥ 40% and reporting Kaplan-Meier curves for at least 36 months. The Kaplan-Meier curves of control groups were extracted and calculated for hazard ratios and 95% confidence intervals. Two virtual trials were developed to validate the reliability and accuracy of our method.

Results

Of 4161 studies, we included six trials containing 7682 HFpEF patients in control groups. The DIG trial had the highest all-cause mortality, cardiovascular mortality, heart failure mortality, and composite endpoints of cardiovascular mortality and heart failure hospitalization (all p < 0.001). The TOPCAT trial had the lowest all-cause mortality, cardiovascular mortality, heart failure hospitalization, and composite of cardiovascular mortality and heart failure hospitalization (all p < 0.001). Adoption of different ejection fraction cut-off values for HFpEF diagnosis did not significantly change the outcomes of control groups in the DIG trial (45% vs. 50%: hazard ratio, 1.05, 95% confidence interval, 0.97–1.13, p = 0.271), or in the CHARM-Preserved trial (40% vs. 50%: hazard ratio, 1.01, 95% confidence interval, 0.93–1.09, p = 0.864) during 36-month follow-up.

Conclusions

The control groups of HFpEF trials have heterogeneous outcomes. Future trials should consider these heterogeneities when designing protocols.

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References

  1. Luo H, Xu Y, Yue F, Zhang C, Chen C. Quality of inclusion criteria in the registered clinical trials of heart failure with preserved ejection fraction: is it time for a change? Int J Cardiol. 2018;254:210–4.

    Article  Google Scholar 

  2. Shah SJ, Katz DH, Selvaraj S, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015;3:269–79.

    Article  Google Scholar 

  3. Zheng SL, Chan FT, Nabeebaccus AA, et al. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Heart. 2018;5:407–15.

    Article  Google Scholar 

  4. Wei Y, Royston P. Reconstructing time-to-event data from published Kaplan-Meier curves. Stata J. 2017;17:786–802.

    PubMed  PubMed Central  Google Scholar 

  5. Luo H, Zhang C, Liu H. A month-by-month analysis of direct oral anticoagulants for secondary prevention of acute coronary syndrome. Eur J Prev Cardiol. 2018;1:2047487318785465.

  6. Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the dig trial. Eur Heart J. 2006;2:178–86.

    Article  Google Scholar 

  7. Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. New Engl J Med. 2014;15:1383–92.

    Article  Google Scholar 

  8. Yamamoto K, Origasa H, Hori M. Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese diastolic heart failure study (J-DHF). Eur J Heart Fail. 2013;1:110–8.

    Article  Google Scholar 

  9. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial. Lancet. 2003;9386:777–81.

    Article  Google Scholar 

  10. Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006;19:2338–45.

    Article  Google Scholar 

  11. Zile MR, Gaasch WH, Anand IS, et al. Mode of death in patients with heart failure and a preserved ejection fraction: results from the irbesartan in heart failure with preserved ejection fraction study (I-PRESERVE) trial. Circulation. 2010;12:1393–405.

    Article  Google Scholar 

  12. Abdul-Rahim AH, Shen L, Rush CJ, Jhund PS, Lees KR, McMurray JJV. Effect of digoxin in patients with heart failure and mid-range (borderline) left ventricular ejection fraction. Eur J Heart Fail. 2018;7:1139–45.

    Article  Google Scholar 

  13. Lund LH, Claggett B, Liu J, Lam CS, Jhund PS, Rosano GM, et al. Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail. 2018;20:1230–9.

    Article  CAS  Google Scholar 

  14. Ahmed A, Rich MW, Fleg JL, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006;5:397–403.

    Article  Google Scholar 

  15. Patel HC, Hayward C, Dungu JN, et al. Assessing the eligibility criteria in phase iii randomized controlled trials of drug therapy in heart failure with preserved ejection fraction: the critical play-off between a “pure” patient phenotype and the generalizability of trial findings. J Card Fail. 2017;7:517–24.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Zhengzhou University People’s Hospital, Zhengzhou, 450003, Henan, China

    Hongxing Luo, Cong Zhang, Juntao Wang & Jialu Zhu

  2. Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Xingtai Jia

Authors
  1. Hongxing Luo
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  2. Cong Zhang
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  3. Juntao Wang
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  4. Jialu Zhu
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  5. Xingtai Jia
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Correspondence to Hongxing Luo.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants performed by any of the authors.

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Luo, H., Zhang, C., Wang, J. et al. Heart Failure with Preserved Ejection Fraction Trials Have Heterogeneous Control Groups: a Comparison of Kaplan-Meier Curves. Cardiovasc Drugs Ther 32, 577–580 (2018). https://doi.org/10.1007/s10557-018-6827-5

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