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Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses

BMJ 2016; 352 doi: (Published 25 February 2016) Cite this as: BMJ 2016;352:i717
  1. Mattias Brunström, PhD student,
  2. Bo Carlberg, associate professor
  1. Department of Public Health and Clinical Medicine, Medicine, Umeå University, SE-901 87 Umeå, Sweden
  1. Correspondence to: M Brunström mattias.brunstrom{at}
  • Accepted 12 January 2016


Objective To assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels.

Design Systematic review and meta-analyses of randomised controlled trials.

Data sources CENTRAL, Medline, Embase, and BIOSIS were searched using highly sensitive search strategies. When data required according to the protocol were missing but trials were potentially eligible, we contacted researchers, pharmaceutical companies, and authorities.

Eligibility criteria Randomised controlled trials including 100 or more people with diabetes mellitus, treated for 12 months or more, comparing any antihypertensive agent against placebo, two agents against one, or different blood pressure targets.

Results 49 trials, including 73 738 participants, were included in the meta-analyses. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all cause mortality (relative risk 0.89, 95% confidence interval 0.80 to 0.99), cardiovascular mortality (0.75, 0.57 to 0.99), myocardial infarction (0.74, 0.63 to 0.87), stroke (0.77, 0.65 to 0.91), and end stage renal disease (0.82, 0.71 to 0.94). If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all cause mortality (0.87, 0.78 to 0.98), myocardial infarction (0.84, 0.76 to 0.93), and heart failure (0.80, 0.66 to 0.97). If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality (1.15, 1.00 to 1.32), with a tendency towards an increased risk of all cause mortality (1.05, 0.95 to 1.16). Metaregression analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality (1.15, 1.03 to 1.29 for each 10 mm Hg lower systolic blood pressure) and myocardial infarction (1.12, 1.03 to 1.22 for each 10 mm Hg lower systolic blood pressure). Patterns were similar for attained systolic blood pressure.

Conclusions Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.


  • We thank the following authors for sharing previously unpublished data, without receiving economic imbursement or any other personal gain: Piero Ruggenenti (BENEDICT), Kathy Wolski (CAMELOT), Lutgarde Thijs (EWPHE and Syst-Eur), Yuhei Kawano (JATOS), Stephan Lüders (PHARAO), Hisatomi Arima (PROGRESS), Lars Hjalmar Lindholm (STOP), Inder Anand (VAL-HEFT), and Hiromi Rakugi (VALISH). We also thank AstraZenica for sharing data from HOT, and the National Heart, Lung, and Blood Institute for sharing data from PEACE, SHEP, and SOLVD.

  • Contributors: Both authors contributed equally to all aspects of study design and conduct, and the writing of the manuscript. BC is guarantor.

  • Funding: This study was funded by Västerbotten County Council. The design and conduct of the study, the interpretation of data, and the writing of the manuscript, was done solely by the authors, independent of the funder.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the regional ethical review board at Umeå University.

  • Data sharing: Results from all meta-analyses are presented in appendix. Additional data, including full forest plots are available on request.

  • Transparency: The lead author (MB) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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