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Title: Cardiovascular and mortality events in type 2 diabetes cardiovascular outcomes trials: a systematic review with trend analysis.
Authors: Vetrone, LM
Zaccardi, F
Webb, DR
Seidu, S
Gholap, NN
Pitocco, D
Davies, MJ
Khunti, K
First Published: 19-Nov-2018
Publisher: Springer (part of Springer Nature)
Citation: Acta Diabetologica, 2018
Abstract: AIMS: To investigate cardiovascular disease and mortality trends in control arm participants of diabetes cardiovascular outcome trials (CVOTs). METHODS: We electronically searched CVOTs published before October 2017. Data on all-cause mortality, cardiovascular mortality and events, and baseline characteristics were collected, along with study calendar years. Trends were estimated using negative binomial regressions and reported as rate ratio (RR) per 5-year intervals. RESULTS: 26 CVOTs, conducted from 1961 to 2015, included 86788 participants with 6543 all-cause deaths, 3265 cardiovascular deaths, and 7657 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). In unadjusted analysis, there was an increasing trend for 3-P MACE rates over time (5-year RR 1.57; 95% CI 1.34, 1.84); a small increasing trend for cardiovascular disease mortality rates (1.13; 1.01, 1.26); and stable rates for all-cause death. Adjusting for age, sex, previous myocardial infarction, and diabetes duration, there was no evidence of trends for 3-P MACE or cardiovascular disease mortality rates, while reducing rates were observed for nonfatal myocardial infarction (5-year RR: 0.72; 0.54, 0.96), total stroke (0.76; 0.66, 0.88), and nonfatal stroke (0.60; 0.43, 0.82). CONCLUSIONS: In contrast to real-world data, there was no evidence of an improvement in all-cause and cardiovascular mortality in type 2 diabetes participants included in control arms of randomised clinical trials across 5 decades. Further studies should investigate whether and how dissimilarities in populations, procedures, and assessments of exposures and outcomes explain the differences between real-world setting and clinical trials.
DOI Link: 10.1007/s00592-018-1253-5
eISSN: 1432-5233
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: The online version of this article ( contains supplementary material, which is available to authorized users.
Description: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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