Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, England, UK.
Servizio di Diabetologia, Catholic University School of Medicine, Largo Francesco Vito 1, 00198, Rome, Italy.
Acta Diabetol. 2019 Mar;56(3):331-339. doi: 10.1007/s00592-018-1253-5. Epub 2018 Nov 19.
To investigate cardiovascular disease and mortality trends in control arm participants of diabetes cardiovascular outcome trials (CVOTs).
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.
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).
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.
研究糖尿病心血管结局试验（CVOT）对照组参与者的心血管疾病和死亡率趋势。
我们通过电子检索，搜索了截至 2017 年 10 月前发表的 CVOT。收集了全因死亡率、心血管死亡率和事件以及基线特征的数据，同时收集了研究日历年份。使用负二项回归估计趋势，并报告每 5 年间隔的率比（RR）。
26 项 CVOT 研究于 1961 年至 2015 年进行，共纳入 86788 名参与者，其中 6543 人死于全因，3265 人死于心血管疾病，7657 人发生 3 点主要不良心血管事件（3-P MACE；心血管死亡、非致死性心肌梗死、非致死性卒中等复合终点）。在未调整分析中，3-P MACE 发生率随时间呈上升趋势（5 年 RR 1.57；95%CI 1.34，1.84）；心血管疾病死亡率呈小幅上升趋势（1.13；1.01，1.26）；全因死亡率保持稳定。调整年龄、性别、既往心肌梗死和糖尿病病程后，3-P MACE 或心血管疾病死亡率均无趋势证据，而非致死性心肌梗死（5 年 RR：0.72；0.54，0.96）、总卒中（0.76；0.66，0.88）和非致死性卒中（0.60；0.43，0.82）发生率呈下降趋势。
与真实世界数据相比，在 50 年中，纳入随机临床试验对照组的 2 型糖尿病患者的全因和心血管死亡率均无改善证据。进一步的研究应探讨人群、程序以及暴露和结局评估的差异如何解释真实世界环境与临床试验之间的差异。
