Unreported exclusion and sampling bias in interpretation of randomized controlled trials in patients with STEMI

Aims: To assess the impact of sampling bias due to reported as well as unreported exclusion of the target population in a multi-center randomized controlled trial (RCT)of ST-elevation myocardial infarction (STEMI). Methods and Results: We compared clinical characteristics and mortality between participants in the DANAMI-3 trial to contemporary non-participants with STEMI using unselected registries. A total of 179 DANAMI-3 participants (8%)and 617 contemporary non-participants (22%)had died (Log-Rank: P < 0.001)after a median follow-up of 1333 days (range: 1–2021 days). In an unadjusted Cox regression model all groups of non-participants had a higher hazard ratio to predict mortality compared to participants: eligible excluded (n = 144)(hazard ratio: 3.41 (95% CI: (2.69–4.32)), ineligible excluded (n = 472)(hazard ratio: 3.42 (95% CI: (2.44–4.80), eligible non-screened (n = 154)(hazard ratio: 3.37 (95% CI: (2.36–4.82)), ineligible non-screened (n = 154)(hazard ratio: 6.48 (95% CI: (4.77–8.80). Conclusion: Sampling bias had occurred due to both reported and unreported exclusion of eligible patients and the difference in mortality between participants and non-participants could not be explained only by the trial exclusion criteria. Thus, screening logs may not be suited to address the risks of sampling bias

MR-proADM as a Prognostic Marker in Patients With ST-Segment-Elevation Myocardial Infarction - DANAMI-3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy

Background Midregional proadrenomedullin ( MR ‐pro ADM ) has demonstrated prognostic potential after myocardial infarction ( MI ). Yet, the prognostic value of MR ‐pro ADM at admission has not been examined in patients with ST‐segment–elevation MI ( STEMI ). Methods and Results The aim of this substudy, DANAMI‐3 (The Danish Study of Optimal Acute Treatment of Patients with ST ‐segment–elevation myocardial infarction), was to examine the associations of admission concentrations of MR ‐pro ADM with short‐ and long‐term mortality and hospital admission for heart failure in patients with ST ‐segment–elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of MR ‐pro ADM was 0.64 nmol/L (25th–75th percentiles, 0.53–0.79). Within 30 days 23 patients (2.0%) died and during a 3‐year follow‐up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of MR ‐pro ADM was, in adjusted models, associated with an increased risk of 30‐day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01–7.11; P =0.049), long‐term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97–5.29; P &lt;0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32–5.58; P =0.007). For 30‐day and 3‐year mortality, the area under the curve for MR ‐pro ADM was 0.77 and 0.78, respectively. For 3‐year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85; P =0.02) after addition of MR ‐pro ADM . Conclusions Elevation of admission MR ‐pro ADM was associated with long‐term mortality and heart failure, whereas the association with short‐term mortality was borderline significant. MR ‐pro ADM may be a marker of prognosis after ST‐segment–elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models. Clinical Trial Registration URL : http:/www.ClinicalTrials.gov /. Unique identifiers: NCT 01435408 and NCT 01960933. </jats:sec

Influence of abnormal glucose metabolism on coronary microvascular function after a recent myocardial infarction

ObjectivesThis study sought to assess the association between abnormal glucose metabolism and abnormal coronary flow reserve (CFR) in patients with a recent acute myocardial infarction (AMI).BackgroundMortality and morbidity after AMI is high among patients with abnormal glucose metabolism, which may be related to abnormal microcirculation.MethodsWe studied 183 patients with a first AMI. In 161 patients with no history of diabetes mellitus (DM), an oral glucose tolerance test was performed, and patients were categorized according to World Health Organization criteria for whole blood glucose into 3 groups. After coronary angiography and revascularization, a comprehensive transthoracic echocardiogram and noninvasive assessment of CFR was performed in the distal part of left descending artery, as an indicator of microvascular function. Adenosine was administered by intravenous infusion (140 μg/kg/min) to obtain the hyperemic flow profiles. The CFR was defined as the ratio of hyperemic to baseline peak diastolic coronary flow velocities.ResultsMedian CFR was 1.9 (interquartile range [IQR] 1.4 to 2.4], and 109 (60%) patients had a CFR ≤2. The lowest CFR was seen in patients with a history of DM (1.4 [IQR 1.4 to 1.7], n = 22) and in patients with newly diagnosed DM (1.6 [IQR 1.3 to 2], n = 39), whereas CFR did not differ in patients with abnormal glucose tolerance (2.1 [IQR 1.4 to 2.6], n = 58) and in patients with normal glucose tolerance (2.2 [IQR 1.7 to 2.6], n = 62). In a stepwise logistic regression model adjusting for age, sex, site and size of AMI, heart rate, risk factors of the metabolic syndrome, degree of angiographic evidence of coronary artery disease, and medical therapy, newly diagnosed DM (odds ratio: 3.0) and a history of DM (odds ratio: 9.9) remained significant predictors of CFR <2, whereas impaired glucose tolerance was not.ConclusionsCFR is decreased in patients with known or newly diagnosed DM even after adjustment of possible confounders, whereas CFR in patients with impaired glucose tolerance seems less affected. (Coronary Flow Reserve and Glucometabolic State [CFRGS]; NCT00845468