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Legacy effect of delayed blood pressure lowering drug treatment in middle-aged adults with mildly elevated blood pressure: systematic review and meta-analysis

Journal of Human Hypertension volume 34, pages 261–270 (2020)Cite this article

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Abstract

To investigate if there is evidence for a ‘legacy effect’ for blood pressure (BP) lowering treatment, that is, worse health outcomes from not initiating drug treatment at a systolic BP threshold of 140 mmHg in middle-age adults. We systematically reviewed studies comparing the effects of delayed BP treatment (placebo/untreated during the trial or no previous treatment at trial entry) vs. early treatment (actively treated during the trial or previous BP treatment at trial entry) on mortality in the short term (5-year in-trial period) and long term (≥10 years in total period). The data were pooled using Peto ORs. A subgroup analysis by 10-year Framingham risk score was performed. Three studies (ALLHAT, Oslo and PREVEND-IT) involving 4746 participants were included. The results were heavily influenced by the ALLHAT trial. We found no significant difference in all-cause mortality between ‘delayed BP’ and ‘early treatment’ in the short-term OR 0.95 (95% CI 0.68–1.32) or long-term OR 0.90 (95% CI 0.78–1.04), with similar results for mortality from cardiovascular disease (CVD). The effects of delayed BP lowering treatment on long-term all-cause and CVD mortality did not vary with baseline risk of CVD. The review showed no clinically adverse ‘legacy effect’ on mortality or major CVD event from not treating middle-aged adults at a systolic BP threshold of 140 mmHg or over. The results were consistent for all CVD risk subgroups. Although these studies are non-randomised post-hoc analyses, they may allay concerns that early treatment of elevated systolic BP is necessary to prevent CVD events in primary prevention populations.

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Fig. 1: Forest plot for outcomes during the in-trial and overall follow-up.
Fig. 2: Forest plot for overall all-cause mortality in subgroup by 10-year Framingham risk score.
Fig. 3: Forest plot for overall CVD mortality in subgroup by 10-year Framingham risk score.

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Acknowledgements

The researchers gratefully acknowledge the RACGP Foundation and Therapeutic Guidelines Ltd for their support of this project. We thank Dr Toshiaki Ohkuma and Prof. John Chalmers for their kind support on the enquiries related to ADVANCE and ADVANCE-ON study. We thank Mark Jones (Biostatistician, Centre for Research in Evidence Based Practice, Bond University) for his advice on statistical issues. No other funding was received from National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); or other granting bodies.

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Authors and Affiliations

  1. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia

    Chau L. B. Ho, Monique Breslin & Mark R. Nelson

  2. School of Public Health, Curtin University, Perth, WA, Australia

    Chau L. B. Ho & Christopher M. Reid

  3. Institute for Evidence-Based Healthcare, Bond University, Gold Coast, QLD, Australia

    Sharon Sanders & Jenny Doust

  4. CCRE Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    Christopher M. Reid & Mark R. Nelson

  5. University of Texas School of Public Health, Houston, TX, USA

    Barry R. Davis & Lara M. Simpson

  6. Department of Cardiology, Haga Teaching Hospital, Postbus 40551 LN, The Hague, The Netherlands

    Frank P. Brouwers

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Correspondence to Chau L. B. Ho.

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CLBH is a Ph.D. candidate at Menzies Institute for Medical Research, she has received a Ph.D. scholarship from Merle Weaver Postgraduate Scholarship. MRN has served on advisory boards for Sanofi and Bayer in the last 3 years. For the remaining authors none were declared.

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Ho, C.L.B., Sanders, S., Breslin, M. et al. Legacy effect of delayed blood pressure lowering drug treatment in middle-aged adults with mildly elevated blood pressure: systematic review and meta-analysis. J Hum Hypertens 34, 261–270 (2020). https://doi.org/10.1038/s41371-020-0323-7

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