Serial pharmacokinetic (PK) sampling in 1159 patients from TRITON‐TIMI 38 was undertaken. A multilinear regression model was used to quantitatively predict prasugrel's active metabolite (Pras‐AM) ...concentrations from its 2 downstream inactive metabolites. Population‐based methods were then applied to Pras‐AM concentration data to characterize the PK. The potential influence of body weight, body mass index, age, sex, renal function, diabetes, tobacco use, and other disease status on Bayesian estimates of Pras‐AM exposures was assessed. The PK of Pras‐AM was adequately described by a multicompartmental model and consistent with results from previous studies. The systemic exposure of prasugrel was not appreciably affected by body mass index, gender, diabetes, smoking, and renal impairment. Pras‐AM mean exposure in patients weighing <60 kg (4.1%) was 30% (90% confidence interval CI 1.16–1.45) higher than exposure in patients ≥60 kg. Mean Pras‐AM exposures for patients ≥75 years (10.5%) were 19% (90% CI: 1.11–1.28) higher compared with patients <75 years.
The involvement of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-2 (IGFBP-2) following acute coronary syndrome (ACS) is rarely studied in clinical practice. ...Therefore, we sought to evaluate the relationship between IGF-1 and IGFBP-2 concentrations at admission and risk stratification based on the Thrombolysis in Myocardial Infarction (TIMI) risk score in patients with ACS.
In all, 304 patients diagnosed with ACS were included in this study. Plasma IGF-1 and IGFBP-2 were measured using commercially available ELISA kits. The TIMI risk score was calculated and the study population was stratified into high (n = 65), medium (n = 138), and low (n = 101) risk groups. Levels of IGF-1 and IGFBP-2 were analyzed for their predictive ability of risk stratification based on the TIMI risk scores. Correlation analysis showed that IGF-1 levels were negatively correlated with TIMI risk levels (r = −0.144, p = 0.012), while IGFBP-2 levels were significantly and positively correlated with TIMI risk levels (r = 0.309, p < 0.001). In multivariate logistic regression analysis, IGF-1 (odds ratio OR: 0.995; 95% confidence interval CI: 0.990–1.000; p = 0.043) and IGFBP-2 (OR: 1.002; 95%CI: 1.001–1.003; p < 0.001) were independent predictors of high TIMI risk levels. In receiver operating characteristic curves, the area under the curve values for IGF-1 and IGFBP-2 in the prediction of high TIMI risk levels were 0.605 and 0.723, respectively.
IGF-1 and IGFBP-2 levels are excellent biomarkers for risk stratification in patients with ACS, which provides further guidance for clinicians to identify patients at high risk and to lower their risk.
•Plasma of IGF-1 was lower, while IGFBP-2 was higher in AMI than in UA group.•IGF-1 levels were negatively correlated with TIMI risk levels.•IGFBP-2 levels were significantly and positively correlated with TIMI risk levels.•IGF-1 and IGFBP-2 were independent predictors of high TIMI risk levels.
Background and Aim:The systemic immune-inflammation index (SII) has been identified as a novel prognostic marker in various illnesses. We investigated the relationship between SII and mortality in ...patients undergoing primary percutaneous coronary intervention (pPCI). In addition, we planned to examine how SII correlated with SYNTAX II and thrombolysis in myocardial infarction (TIMI) risk scores in this population.Materials and Methods:This retrospective observational study included patients with ST-segment elevation myocardial infarction who underwent pPCI. The endpoint was 1 year all-cause mortality. SII (neutrophil x platelet)/lymphocyte was calculated from admission blood samples. Besides clinical and laboratory findings, SII, Syntax II and TIMI risk scores were compared between survivors and non-survivors. The correlation between SII and Syntax II and TIMI risk scores was also evaluated.Results:The study included 334 patients (82.3% male). In the 1 year follow-up, 18 patients (5.4%) died. The SII, Syntax II, and TIMI risk scores were significantly higher in non-survivors than in survivors mean (standard deviation: SD), 2423 (2005) vs 1686 (998), P = 0.005; median (interquartile range) 43 (35-53) vs 30 (25-37), P < 0.001; and 4 (2-5) vs 2 (1-3), P = 0.005, respectively. Furthermore, the Syntax II score, TIMI risk score, and SII was independent predictors of 1 year all-cause mortality. SII showed a significant correlation with Syntax II and TIMI risk scores (R2 = 0.28, P = 0.001 and R2 = 0.37, P < 0.001, respectively).Conclusion:SII might provide additional prognostic data alongside Syntax II and TIMI risk scores in patients undergoing pPCI.
Better early than later Yildiz, Mehmet; Henry, Timothy D.
Catheterization and cardiovascular interventions,
April 1, 2022, 2022-04-00, 20220401, Letnik:
99, Številka:
5
Journal Article
Recenzirano
Key Points
Timing to administer antiplatelet and antithrombin inhibitor in ST‐segment elevation myocardial infarction (STEMI) patients remains a matter of debate despite the guideline's ...recommendation of “as early as possible.”
This pre–post study with heparin and ticagrelor pretreatment in STEMI patients improved pre‐PCI TIMI flow grade with lower peak cardiac troponin levels and higher left ventricular ejection fraction without any difference in bleeding risk.
The results provide further support for the use of standardized STEMI protocols, including pretreatment with aspirin, heparin bolus, and P2Y12 inhibitor at the first‐medical contact in an effort to improve infarct‐related artery patency without risk of bleeding.
Acute myocardial infarction (AMI) patients are at increased risk of death and recurrent ischemic events. We aimed to elaborate a risk score, based on the PEGASUS-TIMI 54 criteria, to predict ...mortality and non-fatal AMI in AMI patients.
We retrospectively analyzed two prospectively collected AMI cohorts. We calculated a cut-off for the developed score and investigated its 1-year prognostic power in the derivation cohort (n = 1257). We externally validated our score in 913 AMI patients with a longer follow-up.
In the derivation cohort, the area under the curve of the score for the primary endpoint (1-year death and non-fatal AMI) was 0.70 (95% CI 0.65–0.76; P < 0.0001) and a cut-off of 6 was identified. The primary endpoint incidence in patients with a score above and below the cut-off was 12% and 3% (P < 0.001) in the derivation cohort and 16% and 6% in the validation cohort (P < 0.001). At multivariate analysis, the HR for the primary endpoint associated with a score ≥ 6 was 4.45 (P < 0.0001) in the derivation cohort and 2.86 (P < 0.0001) in the validation cohort. One-year major bleeding rate was low (<0.2% overall) and similar between risk groups. The prognostic performance of the score cut-off persisted beyond the first year after AMI in the validation cohort, maintaining a similar risk for death and non-fatal AMI (HR 3) at every following year.
Our score, based on the PEGASUS-TIMI 54 criteria, may identify AMI patients at high risk of recurrent ischemic events, who might benefit from thorough preventive strategies.
•Patients with AMI are at risk of death and recurrent ischemic events after discharge, particularly in the first year.•The risk of death and recurrent AMI after AMI can be predicted early by a score based on the PEGASUS-TIMI 54 criteria.•Our score is a simple bedside risk assessment tool easily employable in daily clinical practice.•The evaluation of our score may also support clinical decision-making with respect to a closer clinical follow-up.•Our score identifies AMI patients at high ischemic risk who may derive the greatest benefit from a more intensive therapy.
OBJECTIVES
This study sought to analyze the impact of the preprocedural thrombolysis in myocardial infarction (TIMI) flow on clinical outcome in patients with ST‐elevation myocardial infarction ...(STEMI).
BACKGROUND
Previous studies have shown that the TIMI flow 0/1 prior to primary percutaneous coronary intervention (PCI) is associated with a poor clinical outcome. However, it is unclear whether the same is true in patients with ongoing STEMI of less than 6 hr duration, rapid reperfusion, and modern guideline‐adherent therapy.
METHODS
The ATLANTIC study compared prehospital versus inhospital treatment with ticagrelor in patients with acute STEMI. For this analysis, patients were divided into three groups according to the preprocedural TIMI flow grade of the infarct vessel: TIMI 0/1, TIMI 2, and TIMI 3.
RESULTS
From a total of 1,680 patients, 1,113 had TIMI 0/1, 279 TIMI 2, and 288 TIMI 3 flow before primary PCI. At 30 days, the composite ischemic endpoint (5.5, 2.9, and 2.1%, p < .05) and all‐cause death (3.0, 1.4, and 2.1%, p = .30) were highest in patients with TIMI flow 0/1. After adjustment, preprocedural TIMI flow <3 (versus 3) was not an independent predictor of major adverse ischemic events within 30 days (odds ratio 1.89, 95% confidence interval 0.74–4.85). However, definite stent thrombosis occurred only in patients with initial TIMI flow 0/1 (1.0%). Among these patients, those with prehospital administration of ticagrelor were less often affected (0.3% vs. 1.3%, p < .05).
CONCLUSION
In this post‐hoc analysis, preprocedural TIMI flow was not independently associated with a higher rate of adverse ischemic events.
Large-scale outcome trials of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes have identified consistent effects on major adverse cardiovascular events, heart ...failure, and progression of kidney disease. However, the magnitude of effects on cardiovascular and all-cause death appeared to vary between some of the studies.
We explored the impact of differences in trial methodologies, participant characteristics, types of deaths, follow-up duration, effects on intermediate markers of risk, and drug selectivity for SGLT2 on the magnitude of the protective effect against fatal events achieved in the 4 trials.
The trial populations differed substantively in the proportions with baseline atherosclerotic cardiovascular disease history (99.2% in EMPA-REG OUTCOME to 40.6% in DECLARE-TIMI 58), and macroalbuminuria (88.0% in CREDENCE to 7.6% in the CANVAS Program). Meta-regression analyses identified no clear effect of these (both P > 0.09) or other participant characteristics on mortality benefits (all P > 0.55). Other differences between the trials (duration, selectivity of the SGLT2 inhibitor, or effects on intermediate markers of risk) also did not explain the heterogeneity in effects on mortality observed (all P > 0.30).
No clear explanation for the statistical evidence of heterogeneity in effects of SGLT2 inhibition on fatal outcomes between the trials could be identified. While the analyses had limited statistical power, these results raise the possibility that the observed variations in treatment effects on fatal outcomes between trials may be at least partly due to chance.
•Heterogeneity in mortality was observed in large-scale trials of SGLT2 inhibitors.•Meta-regression analyses found no explanation for variations in fatal outcomes.•Variations in SGLT2 inhibitor effects on fatal outcomes may be partly due to chance.
Women have a worse prognosis after ST-segment elevation myocardial infarction (STEMI) than men. The prognostic role of thrombus burden (TB) in influencing the sex-related differences in clinical ...outcomes after STEMI has not been clearly investigated.
The aim of this study was to assess the sex-related differences in TB and its clinical implications in patients with STEMI.
Individual patient data from the 3 major randomized clinical trials of manual thrombus aspiration were analyzed, encompassing a total of 19,047 patients with STEMI, of whom 13,885 (76.1%) were men and 4,371 (23.9%) were women. The primary outcome of interest was 1-year cardiovascular (CV) death. The secondary outcomes of interest were recurrent myocardial infarction, heart failure, all-cause mortality, stroke, stent thrombosis (ST), and target vessel revascularization at 1 year.
Patients with high TB (HTB) had worse 1-year outcomes compared with those presenting with low TB (adjusted HR for CV death: 1.52; 95% CI: 1.10-2.12; P = 0.01). In unadjusted analyses, female sex was associated with an increased risk for 1-year CV death regardless of TB. After adjustment, the risk for 1-year CV death was higher only in women with HTB (HR: 1.23; 95% CI: 1.18-1.28; P < 0.001), who also had an increased risk for all-cause death and ST than men.
In patients with STEMI, angiographic evidence of HTB negatively affected prognosis. Among patients with HTB, women had an excess risk for ST, CV, and all-cause mortality than men. Further investigations are warranted to better understand the pathophysiological mechanisms leading to excess mortality in women with STEMI and HTB.
Display omitted
Killip classification has been used to stratify the risk of patients with acute myocardial infarction (AMI). There were many reports that Killip class 3 or 4 is closely associated with poor clinical ...outcomes. In other words, Killip class 1 or 2 is associated with favorable clinical outcomes in patients with AMI, especially when patients received primary percutaneous coronary intervention (PCI). However, some patients with Killip class 1/2 suffer from serious in-hospital complications. This study aimed to identify factors associated with serious in-hospital complications of ST-segment elevation myocardial infarction (STEMI) in patients with Killip class 1/2. The primary endpoint was serious in-hospital complications defined as the composite of in-hospital death and mechanical complications. We included 809 patients with STEMI, and divided them into the non-complication group (n = 791) and the complication group (n = 18). In-hospital death was observed in 14 patients (1.7%), and mechanical complications were observed in 4 patients (0.5%). Final TIMI flow ≤ 2 was more frequently observed in the complication group (33.3%) than in the non-complication group (5.4%) (p < 0.001). Multivariate logistic regression analysis revealed that serious in-hospital complication was associated with final TIMI flow grade ≤ 2 (Odds ratio 6.040, 95% confidence interval 2.042-17.870, p = 0.001). In conclusion, serious in-hospital complication of STEMI was associated with insufficient final TIMI flow grade in patients with Killip class 1/2. If final TIMI flow grade is suboptimal after primary PCI, we may recognize the potential risk of serious complications even when patients presented as Killip class 1/2.
PDF
