Cardiovascular and mortality events in type 2 diabetes cardiovascular outcomes trials: a systematic review with trend analysis.

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.

Long-term mortality after acute myocardial infarction among individuals with and without diabetes: A systematic review and meta-analysis of studies in the post-reperfusion era.

AIMS: To conduct a systematic review and meta-analysis with the aim of providing robust estimates of the association between diabetes and long-term (≥1 year) mortality after acute myocardial infarction (AMI). MATERIAL AND METHODS: Medline, Embase and Web of Science databases were searched (January 1985 to July 2016) for terms related to long-term mortality, diabetes and AMI. Two authors independently abstracted the data. Hazard ratios (HRs) comparing mortality in people with and without diabetes were pooled across studies using Bayesian random-effects meta-analysis. RESULTS: A total of 10 randomized controlled trials and 56 cohort studies, including 714 780 patients, reported an estimated total of 202 411 deaths over the median (range) follow-up of 2.0 (1-20) years. The risk of death over time was significantly higher among those with diabetes compared with those without (unadjusted HR 1.82, 95% credible interval [CrI] 1.73-1.91). Mortality remained higher in the analysis restricted to 23/64 cohorts reporting data adjusted for confounders (adjusted HR 1.48, 95% CrI 1.43-1.53). The excess long-term mortality in diabetes was evident irrespective of the phenotype and modern treatment of AMI, and persisted in early survivors (unadjusted HR 1.82, 95% CrI 1.70-1.95). CONCLUSIONS: Despite medical advances, individuals with diabetes have a 50% greater long-term mortality compared with those without. Further research to understand the determinants of this excess risk are important for public health, given the predicted rise in global diabetes prevalence.

Survival in South Asian and White European patients after acute myocardial infarction.

OBJECTIVE: To examine the association between ethnicity and survival following acute myocardial infarction (AMI) in White European (WE) and South Asian (SA) patients from a multiethnic UK population. METHODS: Retrospective, cohort study of 4111 (N=730, 17.8% of SA ethnicity) hospitalised patients, with AMI from a tertiary coronary care centre in the UK, admitted between October 2002 and September 2008. The primary end point was all-cause mortality. The association of ethnicity with survival post AMI was assessed using the Cox regression analysis. RESULTS: Compared with WE patients, SA patients were on average younger (62.0 years vs 67.3 years) and had higher prevalence of cardiovascular risk factors including diabetes (39.7% vs 16.1%). During follow-up (median 912, range 1-2556, days), crude mortality rate was 22.6% in SA patients and 26.0% in WE patients (p = 0.061). SA ethnicity did not show univariate (HR 0.85 (0.72 to 1.01)) or multivariate (HR, 1.12 (0.94 to 1.34)) association with mortality. Findings were similar for mortality during 0-30 days (1.30 (0.99 to 1.70)), > 30 days-1 year (0.97 (0.67 to 1.40)), > 1 year-3 years (1.21 (0.83 to 1.76)), > 3 years (0.82 (0.47 to 1.41)), and for long-term mortality in survivors from 30 days (1.02 (0.81 to 1.29)). CONCLUSIONS: When adjusted for differing prevalence of cardiovascular risk factors in the two ethnic groups, survival following AMI was similar for SA and WE patients in the UK.