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The effects of renin–angiotensin system inhibitors on mortality, cardiovascular events, and renal events in hypertensive patients with diabetes: a systematic review and meta-analysis of randomized controlled trials


Renin–angiotensin system (RAS) inhibitors are often used as a first-line treatment for hypertensive patients with diabetes because of purported benefits, such as reno-protection. However, there is no clear evidence for the superiority of RAS inhibitors to other classes of antihypertensives for clinically important outcomes in this population. We conducted a meta-analysis to assess whether RAS inhibitors are better than other classes of antihypertensives for reducing mortality, and cardiovascular and renal events in hypertensive patients with diabetes. From June to December 2017, we searched Medline, Cochrane Library, and the database of the Japan Medical Abstracts Society (ICHUSHI) for relevant published randomized controlled trials that directly compared the effects of RAS inhibitors to other classes of antihypertensives as first-line treatments for reducing adverse outcomes among hypertensive patients with diabetes. Our predetermined outcomes included all-cause death, cardiovascular death, incidence of cardiovascular disease, and renal dysfunction. We identified 16 trials, including a total of 35,052 patients. No significant benefits for RAS inhibitors were found compared to other classes of antihypertensives for all-cause death (relative risk (RR) 0.95, 95% confidence interval (CI) 0.85–1.05, p = 0.29), cardiovascular death (RR 0.84, 95% CI 0.68–1.04, p = 0.11), incidence of cardiovascular disease (RR 0.93, 95% CI 0.84–1.03, p = 0.16), and incidence of renal dysfunction (RR 0.91, 95% CI 0.77–1.06, p = 0.22). In conclusion, RAS inhibitors are not superior to other classes of antihypertensive drugs for reducing all-cause and cardiovascular mortalities, cardiovascular events, and renal events in hypertensive patients with diabetes.

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We thank Professor Masahiro Yoshida for his valuable advice and support in conducting this systematic review and meta-analysis.

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Correspondence to Ayako Kunimura.

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Kunimura, A., Himuro, N., Fujiyoshi, A. et al. The effects of renin–angiotensin system inhibitors on mortality, cardiovascular events, and renal events in hypertensive patients with diabetes: a systematic review and meta-analysis of randomized controlled trials. Hypertens Res 42, 669–680 (2019).

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  • Diabetes mellitus
  • Hypertension
  • Meta-analysis
  • Renin angiotensin system blockers
  • Systematic review

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