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Predicted impact of various clinical practice strategies on cardiovascular risk for the treatment of hypertension: a clinical trial simulation study

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Abstract

Hypertension control rate in the US is low with the current clinical practice (JNC 7) and cardiovascular disease (CVD) remain is the leading cause of morbidity and mortality. A 6-month clinical trial simulation case study testing different virtual clinical practice strategies was performed in an attempt to increase the control rate. The CVD risk was calculated using the Framingham CVD risk model at baseline and 6 months post-treatment. The estimated CVD events for the baseline patient sample without any treatment was 998 (95 % CI: 967–1,026) over 6 months in 100,000 patients. Treating these patients for 6 months with current clinical practice, high dose strategy, high dose with low target BP strategy resulted in a reduction in CVD events of 191(95 % CI: 169–205), 284 (95 % CI: 261–305), and 353 (95 % CI: 331–375), respectively. Hence the two alternative strategies resulted in an increase in treatment effect by 49 % (95 %CI: 44–59 %) and 85 % (95 %CI: 79–99 %), respectively. The increased safety with the current low dose strategy may potentially be offset by increased CVD risk in the time necessary to control hypertension.

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Acknowledgments

The study was funded by FDA-Pharmacometrics Critical Path Fellowship. The authors would like to thank Dr. Karen A. Matthews (Distinguished Professor of Psychiatry, Professor of Epidemiology and Psychology, Director, Pittsburgh Mind–Body Center Director, Cardiovascular Behavioral Medicine Research Program, Department of Psychiatry, University of Pittsburgh School of Medicine) for providing ABPM data to evaluate baseline BP model. The project was also supported by Indiana Clinical and Translational Sciences Institute (Dr. Robert Bies).

Conflict of Interest

Dr. Robert Bies is funded through the Indiana CTSI facilitated by a gift from Eli Lilly and Company, NICHD, Merck.

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Authors and Affiliations

  1. Clinical Pharmacology, Roche Innovation Centre Shanghai, F. Hoffmann-La Roche Ltd., Shanghai, 201203, China

    Yuyan Jin

  2. Division of Clinical Pharmacology, Indiana Clinical and Translational Sciences Institute, Indiana University, Indianapolis, IN, USA

    Robert Bies

  3. Metrum Institute, Tariffville, CT, USA

    Marc R. Gastonguay

  4. U.S. Food and Drug Administration, Silver Spring, MD, USA

    Yaning Wang, Norman Stockbridge & Rajanikanth Madabushi

  5. School of Pharmacy and School of Medicine, University of Maryland, Baltimore, MD, USA

    Jogarao Gobburu

  6. WO51, RM2172, CDER, FDA, 10903 New Hampshire Ave, Silver Spring, MD, 20903, USA

    Rajanikanth Madabushi

Authors
  1. Yuyan Jin
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  2. Robert Bies
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  3. Marc R. Gastonguay
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  4. Yaning Wang
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  5. Norman Stockbridge
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  6. Jogarao Gobburu
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  7. Rajanikanth Madabushi
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Corresponding author

Correspondence to Rajanikanth Madabushi.

Appendix

Appendix

See Figs. 5 and 6.

Fig. 5
figure 5

Visual predictive check for baseline model with observed ABPM data

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Fig. 6
figure 6

a Simulated circadian rhythms for 12 virtual subjects on a selected random day (occasion 1). b Simulated circadian rhythms for 12 virtual subjects on another random day (occasion 2)

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Jin, Y., Bies, R., Gastonguay, M.R. et al. Predicted impact of various clinical practice strategies on cardiovascular risk for the treatment of hypertension: a clinical trial simulation study. J Pharmacokinet Pharmacodyn 41, 693–704 (2014). https://doi.org/10.1007/s10928-014-9394-9

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  • DOI: https://doi.org/10.1007/s10928-014-9394-9

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