Dual antiplatelet therapy with aspirin, a platelet cyclooxygenase-1 inhibitor and P2Y12 receptor blockers, remains the major drug strategy to prevent ischemic event occurrence in patients with acute coronary syndromes and in patients undergoing coronary stenting, but there some limitations that can be overcome by targeting novel targets. Unlike direct thrombin inhibitors that bind directly to thrombin, targeting the platelet thrombin receptor, protease activated receptor (PAR)-1, may offer a better choice for the attenuation of atherosclerosis progression, thrombus-mediated ischemic events and restenosis without interfering with primary hemostasis. Vorapaxar - a synthetic analogue of himbacine, is a high affinity and highly selective PAR-1 antagonist that can effectively inhibit thrombin-induced platelet aggregation. In the TRACER trial, the addition of vorapaxar to standard therapy in patients with non-stent thrombosis-elevation- acute coronary syndromes did not significantly reduce the primary composite end point occurrence of cardiovascular (CV) death, myocardial infarction (MI), stroke, hospitalization for ischemia, or urgent revascularization, but significantly increased the GUSTO moderate and severe bleeding (p < 0.001) and intracranial hemorrhage (ICH). In the TRA 2°P-TIMI 50 trial, in patients with a history of MI and peripheral arterial disease (PAD) (67% of the total population), the end point of CV death, MI, or stroke was significantly (20%) reduced with vorapaxar whereas GUSTO moderate or severe bleeding was increased (1.5-fold), but not ICH or fatal bleeding and the net clinical outcome favoring the vorapaxar therapy. Based on these favorable results, the FDA approved vorapaxar for the reduction of thrombotic cardiovascular events in patients with prior MI or with PAD for long term therapy. A careful patient selection is needed to balance efficacy versus safety. At this time, patients with high risk for recurrent ischemic event occurrence such as patients with diabetes mellitus and previous MI can be safely treated with vorapaxar for long-term therapy.
High central aortic pulse pressure (CPP) and thrombin-induced platelet-fibrin clot strength (TIP-FCS) have been associated with ischemic outcomes in patients with coronary artery disease in separate studies. But, the ischemic risk associated with these factors has never been analyzed in a single study and their interrelation is unknown. The primary aim of the study was to establish cut points for CPP and TIP-FCS measured at the time of catheterization associated with long term major adverse cardiovascular events. We enrolled 334 consecutive patients undergoing cardiac catheterization and assessed thrombogenicity by thrombelastography. Patients were followed up to 3 years. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and ischemic stroke and the secondary endpoint was occurrence of the primary endpoint or recurrent ischemic events requiring hospitalization. Patients with primary and secondary endpoint occurrence had higher CPP (83 ± 20 vs. 60 ± 18 mmHg, p < 0.0001; 70 ± 21 vs. 59 ± 18 mmHg, p < 0.0001, respectively) and TIP-FCS (68.5 ± 5.8 vs. 65.5 ± 5.0 mm, p = 0.008; 67.4 ± 5.9 vs. 65.2 ± 4.8 mm, p = 0.001, respectively). CPP >60 mmHg and TIP-FCS >69 mm were both independent predictors of primary endpoint occurrence (p = 0.0001 and p = 0.02, respectively). ROC analysis for CPP and TIP-FCS showed a C-statistic of 0.81 (p < 0.0001) and 0.68 (p = 0.007) for the primary endpoint, respectively. Patients with CPP >60 mmHg had higher TIP-FCS (66.8 ± 5.1 vs. 64.8 ± 5.0 mm, p < 0.001) and primary and secondary endpoint occurrence (13 vs. 1.1%, p < 0.0001 and 31.8 vs. 14.4%, p = 0.0002, respectively). CPP >60 mmHg + TIP-FCS > 69 mm was associated with a markedly increased risk of primary endpoint occurrence [HR (95% CI) 5.4(2.3-12.5), p = 0.0001]. High CPP and thrombogenicity are interrelated; each are independently associated with increased cardiovascular risk; and simultaneous presence markedly enhances risk. The mechanistic link between CPP and thrombogenicity deserves further study.
Background:Recent advances in extracorporeal membrane oxygenation (ECMO) have led to increasing interest in its use during cardiopulmonary resuscitation (CPR). However, decisions regarding extracorporeal CPR (ECPR) in children are difficult as a result of limited studies, especially in Asia Pacific. The objective of this study was to investigate trends in survival and demographic details for children with ECPR in Asia Pacific recorded in the Extracorporeal Life Support Organization (ELSO) registry from 1999 to 2016 and identify the risk factors associated with in-hospital mortality.Methods:The data of children younger than 18 years of age who received ECPR over the past 18 years in Asia Pacific were retrospectively analyzed. The data were extracted from the ELSO registry and divided into two 9-year groups (Group 1: 1999–2007 and Group 2: 2008–2016) to assess temporal changes using univariate analysis. Then, univariate and multiple logistic regression analyses were performed between survivors and nonsurvivors to identify factors independently associated with in-hospital mortality.Results:A total of 321 children were included in final analysis, with an overall survival rate of 50.8%. Although survival rates were similar between Group 1 and Group 2 (43.1% vs. 52.5%, χ2 = 1.67, P = 0.196), the median age (1.7 [0.3, 19.2] months for Group 1 vs. 5.6 [0.8, 64.9] months for Group 2, t = −2.93, P = 0.003) and weight (3.7 [3.0, 11.5] kg for Group 1 vs. 6.0 [3.4, 20.3] kg for Group 2, t = −3.14, P = 0.002) of children increased over time, while the proportion of congenital heart disease (75.9% for Group 1 vs. 57.8% for Group 2, χ2 = 6.52, P = 0.011) and cardiogenic shock (36.2% for Group 1 vs. 7.2% for Group 2, χ2 = 36.59, P < 0.001) decreased. Patient conditions before ECMO were worse, while ECMO complications decreased across time periods, especially renal complications. Multiple logistic regression analysis of ECMO complications showed that disseminated intravascular coagulation (DIC), myocardial stunning, and neurological complications were independently associated with increased odds of hospital mortality.Conclusions:The broader indications and decreased complication rates make EPCR to be applicated more and more extensive in children in Asia Pacific region. ECMO complications such as myocardial stunning are independently associated with decreased survival.
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