Dataset Information

Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque.

ABSTRACT:

Objectives

The goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque.

Background

High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy.

Methods

In a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary ¹⁸F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary ¹⁸F-fluoride uptake.

Results

In total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary ¹⁸F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary ¹⁸F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33).

Conclusions

Dual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303).

SUBMITTER: Moss AJ

PROVIDER: S-EPMC7342015 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Project description:BackgroundContrast volume used during percutaneous coronary intervention has a direct relationship with contrast-associated acute kidney injury. While several models estimate the risk of contrast-associated acute kidney injury, only the strategy of limiting contrast volume to 3 × estimated glomerular filtration rate (eGFR) gives actionable estimates of safe contrast volume doses. However, this method does not consider other patient characteristics associated with risk, such as age, diabetes or heart failure.MethodsUsing the National Cardiovascular Data Registry acute kidney injury risk model, we developed a novel strategy to define safe contrast limits by entering a contrast term into the model and using it to meet specific (eg, 10%) relative risk reductions. We then estimated acute kidney injury rates when our patient-centered model-derived thresholds were and were not exceeded using data from CathPCI version 5 between April 2018 and June 2019. We repeated the same analysis in a sub-set of patients who received ≤3 × eGFR contrast.ResultsAfter excluding patients on hemodialysis, below average risk (<7%), missing data and multiple percutaneous coronary interventions, our final analytical cohort included 141,133 patients at high risk for acute kidney injury. The rate of acute kidney injury was 10.0% when the contrast thresholds derived from our patient-centered model were met and 18.2% when they were exceeded (P < .001). In patients who received contrast ≤3 × eGFR (n = 82,318), contrast-associated acute kidney injury rate was 9.8% when the contrast thresholds derived from our patient centered model were met and 14.5% when they were exceeded (P < .001).ConclusionsA novel strategy for developing personalized contrast volume thresholds, provides actionable information for providers that could decrease rates of contrast-associated acute kidney injury. This strategy needs further prospective testing to assess efficacy in improving patient outcomes.

Project description:ObjectiveThis study sought to investigate the association between volume and attenuation of epicardial fat and presence of obstructive coronary artery disease (CAD) and high-risk plaque features (HRPF) on CT angiography (CTA) in patients with atypical chest pain and whether the association, if any, is independent of conventional cardiovascular risk factors and coronary artery calcium score (CACS).MethodsPatients referred for coronary CTA with atypical chest pain and clinical suspicion of CAD were included in the study. Quantification of CACS, epicardial fat volume (EFV) and epicardial fat attenuation (EFat) was performed on non-contrast images. CTA was evaluated for presence of obstructive CAD and presence of HRPF.Results255 patients (median age [interquartile range; IQR]: 51[41-60] years, 51.8% males) were included. On CTA, CAD, obstructive CAD (≥50% stenosis) and CTA-derived HRPFs was present in 133 (52.2%), 37 (14.5%) and 82 (32.2%) patients respectively. A significantly lower EFat was seen in patients with obstructive CAD than in those without (-86HU [IQR:-88 to -82 HU] vs -84 [IQR:-87 HU to -82 HU]; p = 0.0486) and in patients with HRPF compared to those without (-86 HU [IQR:-88 to -83 HU] vs -83 HU [-86 HU to -81.750 HU]; p < 0.0001). EFat showed significant association with obstructive CAD (unadjusted Odd's ratio (OR) [95% CI]: 0.90 [0.81-0.99];p = 0.0248) and HRPF (unadjusted OR [95% CI]: 0.83 [0.76-0.90];p < 0.0001) in univariate analysis, which remained significant in multivariate analysis. However, EFV did not show any significant association with neither obstructive CAD nor HRPF in multivariate analysis. Adding EFat to conventional coronary risk factors and CACS in the pre-test probability models increased the area-under curve (AUC) for prediction of both obstructive CAD (AUC[95% CI]: 0.76 [0.70-0.81] vs 0.71 [0.65-0.77)) and HRPF (AUC [95% CI]: 0.92 [0.88-0.95] vs 0.89 [0.85-0.93]), although not reaching statistical significance.ConclusionEFat, but not EFV, is an independent predictor of obstructive CAD and HRPF. Addition of EFat to traditional cardiovascular risk factors and CACS improves estimation for pretest probability of obstructive CAD and HRPF.Advances in knowledgeEFat is an important attribute of epicardial fat as it reflects the "quality" of fat, taking into account the effects of brown-white fat transformation and fibrosis, as opposed to mere evaluation of "quantity" of fat by EFV. Our study shows that EFat is a better predictor of obstructive CAD and HRPF than EFV and can thus explain the inconsistent association of increased EFV alone with CAD.