Real-world effectiveness and safety of macitentan in patients with pulmonary artery hypertension: a multicenter, retrospective, observational study in China.

BACKGROUND: Macitentan, either as monotherapy or part of combination therapy, improved clinical outcomes in patients with pulmonary artery hypertension (PAH) in clinical trials. Evidence on the effectiveness and safety of macitentan administered in real-world clinical practice in China is limited. METHODS: This real-world, retrospective, multicenter chart review study was conducted at seven hospitals in China. Adult patients with a diagnosis of PAH who initiated macitentan and had medical assessments at 3-7 months after macitentan initiation were included. The primary outcomes were changes in the World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide from baseline to first follow-up visit (months 3-7). Serious adverse events (SAEs) and adverse drug reactions (ADRs) of macitentan were collected. RESULTS: From 30 August 2021 to 31 March 2022, 214 eligible patients were included in the safety analysis set and 105 patients were included in the analysis of effectiveness. At the first follow-up visit compared with baseline, significant changes in WHO-FC were observed (p = .04), 93.5% patients had their WHO-FC improved (25.8%) or maintained (67.7%). 6MWD changed by a mean (standard deviation [SD]) of 45.0 (81.4) meters (p < .001), with 94.7% having their 6MWD improved (34.7%) or maintained (60.0%). The mean (SD) of NT-proBNP decreased from 1667.4 (3233.0) ng/L to 1090.0 (2230.1) ng/L (p < .001). In the safety analysis set, 24 (11.2%) patients experienced at least one ADR and/or SAE. ADRs and SAEs were reported in 11 (5.1%) and 18 (8.4%), respectively. No deaths or unexpected safety events were observed. CONCLUSION: This study provided real-world evidence on the clinical benefits and good tolerance of macitentan in Chinese patients with PAH treated in routine clinical practice.

The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

Optimal combination of right ventricular functional parameters using echocardiography in pulmonary arterial hypertension.

AIMS: Novel echocardiographic parameters of right ventricular (RV) function, including speckle-tracking-derived, three-dimensional, and RV-pulmonary artery coupling parameters, have emerged for the evaluation of pulmonary arterial hypertension (PAH). The relative role of these parameters in the risk stratification of PAH patients is unclear. We compared the performance of multiple RV parameters and sought to establish an optimal model for identifying the risk profile of patients with PAH. METHODS AND RESULTS: Comprehensive risk assessments were performed for 70 patients with PAH. The risk profile of every patient was determined based on the guideline recommendations. Conventional parameters, including fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE), novel speckle-tracking-derived RV longitudinal strain (RVLS), and three-dimensional RV ejection fraction (3D-RVEF), were used to evaluate RV function. Pressure-strain loops were measured for the assessment of RV myocardial work, including RV global wasted work (RVGWW). RV-pulmonary artery coupling was assessed by indexing RV parameters to the estimated pulmonary artery systolic pressure (PASP). The median age was 34 (30-43) years, and 62 (88.6%) patients were female. Forty-five patients were classified into the low-risk group, while 25 patients were classified into the intermediate-high-risk group. Most RV parameters could be used to determine the risk profile and exhibited significantly improved diagnostic performance after indexing to PASP (including FAC/PASP, TAPSE/PASP, and 3D-RVEF/PASP). RVLS/PASP showed the best performance, with an area under the curve of 0.895. In multivariate analysis (Model 1), only RVGWW (>90.5 mmHg%), RVLS (> -16.7%), and TAPSE (<17.5 mm) remained significant (all P < 0.05). Model 1 outperformed every single RV parameter, with a significantly larger area under the curve (all P < 0.05). With PASP indexing in Model 2, RVLS/PASP > -0.275 [odds ratio (OR) 20.63, 95% confidence interval (CI) 4.62-92.11, P < 0.001] and RVGWW > 90.5 mmHg% (OR 6.17, 95% CI 1.37-27.76, P = 0.018) independently identified a higher risk profile. The addition of RVGWW to two models determined incremental value in identification (continuous net reclassification improvement 1.058, 95% CI 0.639-1.477, P < 0.001). CONCLUSIONS: The combination models for RV function outperformed any single parameter in identifying the risk profile of patients with PAH. Comprehensive assessment of RV-pulmonary artery coupling using multiparametric methods is clinically meaningful in patients with PAH.

Selexipag-based triple combination therapy improves prognosis in Chinese pulmonary arterial hypertension patients.

Aim: Selexipag is an oral selective prostacyclin receptor agonist approved for treatment of patients with pulmonary arterial hypertension (PAH). In the present study, we aim to assess the safety and efficacy of selexipag in triple combination therapy with endothelial receptor antagonists (ERAs) and PDE5is for Chinese PAH patients. Methods and results: A single center retrospective study was performed on group 1 PAH patients (n = 68) initiating triple combination therapy with selexipag from 1 February 2020 to 31 August 2021 in Qilu Hospital of Shandong University (Shandong, China). Adolescents, children, and PAH patients with unrepaired congenital heart disease were excluded. The French pulmonary hypertension network (FPHN) non-invasive risk assessment, echocardiogram parameters, and clinical data, including tolerability, safety, and death/hospitalization events associated with PAH, were collected. Of the 68 patients, 31 (45.6%) patients had tolerable side effects while only a single patient discontinued selexipag due to severe diarrhea. In the analysis of the efficacy set of 62 patients, the median selexipag treatment time from selexipag initiation to last risk assessment was 27 (21, 33) weeks. Compared to baseline parameters, the percentage of WHO FC III/IV decreased from 77.4% (48) to 24.2% (15) (p = 0.000), median 6-min walk distance (6MWD) increased 82 m [from 398 (318, 450) to 480 (420, 506) m; p = 0.000], and NT-proBNP levels decreased from 1,216 (329, 2,159) to 455 (134, 1,678) pg/mL (p = 0.007). Patients who improved to three low-risk criteria increased from 9.7 to 38.7%. Right ventricular diameter (RV) diameter also decreased and was accompanied by an improved tricuspid annular plane systolic excursion (TAPSE). Patients transitioning from subcutaneous treprostinil to selexipag continued to show improvements in WHO FC, 6MWD (404 ± 94 vs. 383 ± 127 m) and NT-proBNP levels (2,319 ± 2,448 vs. 2,987 ± 3,770 pg/mL). Finally, the 1-year event free survival rate was 96.7% for patients initiating the triple combination therapy within 3 years of PAH diagnosis. Conclusion: Triple combination therapy with selexipag was safe and effective in Chinese PAH patients, which was confirmed by acceptable tolerability, and improved exercise capacity, right heart function, risk assessment, and prognosis.

Effect of ambrisentan on echocardiographic and Doppler measures from patients in China with pulmonary arterial hypertension.

BACKGROUND: We retrospectively evaluated the echocardiographic data of ambrisentan-treated patients with pulmonary arterial hypertension (PAH) (NCT01808313). METHODS: Change from baseline in right ventricle (RV) systolic function, right heart structure, and pulmonary artery systolic pressure (PASP) prognosis to Weeks 12 and 24 was evaluated by echocardiography. RESULTS: In the overall population, the mean tissue Doppler-derived tricuspid lateral annular systolic velocity (S') increased by 0.6 cm/s at both Weeks 12 (p < 0.001) and 24 (p = 0.004) and tricuspid annular plane systolic excursion increased by 0.13 cm at Week 12 and 0.15 cm at Week 24 (both p < 0.001). A marked decrease in transverse and longitudinal RV and RA diameter at Weeks 12 and 24 was observed. A significant decrease in diastolic eccentricity index at both Weeks 12 (-0.1; p = 0.02) and 24 (-0.1; p = 0.001). The decrease in PASP from baseline was significant at both Weeks 12 (-9.5 mmHg; p<0.001) and 24 (-7.6 mmHg; p<0.001), while a decrease in the estimated right atrium pressure was found to be significant at Week 24 (-0.8mmHg; p = 0.01). CONCLUSION: Significant improvements in a number of RV echocardiographic parameters were observed at Weeks 12 and 24 after ambrisentan treatment in patients with PAH.

Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis.

BACKGROUND: The efficacy and safety of ambrisentan has been previously evaluated in Chinese patients with pulmonary arterial hypertension (PAH). This post-hoc analysis assessed the efficacy and safety of ambrisentan in a subgroup of connective tissue disease (CTD) patients with PAH. METHODS: In this open-label, single-arm study, patients received ambrisentan 5 mg once daily for 12 weeks, followed by 12-week dose titration period (dose up to 10 mg). Efficacy endpoints included change from baseline in exercise capacity (measured by 6-min walk test [6MWT]), N-terminal pro B type natriuretic peptide (NT-proBNP) plasma levels, WHO Functional Class (FC) and Borg Dyspnoea Index (BDI) scores from baseline to weeks 12 and 24. Safety endpoints included time to clinical worsening and incidence of adverse events (AEs). RESULTS: In total, 71 Chinese patients with CTD-PAH were included in this analysis. Ambrisentan treatment significantly improved exercise capacity (6MWT) from baseline (mean: 366.4 m) to week 12 (63.8 m, p < 0.001) and week 24 (73.2 m, p < 0.001). A significant reduction in NT-proBNP levels was observed from baseline (mean: 1837.5 ng/L) to week 12 (- 1156.8 ng/L, p < 0.001) and week 24 (- 1095.5 ng/L, p < 0.001). BDI scores decreased significantly at week 12 (- 0.6, p < 0.001) and week 24 (- 0.4, p = 0.002) from baseline (mean: 2.7). The WHO FC improved in 29 (40.8%) and 34 (47.9%) patients at weeks 12 and 24, respectively. Adverse events were reported in 52 (73.2%) patients. One patient (1.4%) experienced clinical worsening at week 24. CONCLUSION: Ambrisentan showed significant improvement in exercise capacity and no clinical worsening in the majority of Chinese patients with CTD-PAH in the 24-week treatment period. The AEs observed in the CTD-PAH subgroup were consistent with the known safety profile of ambrisentan in the overall Chinese PAH population. TRIAL REGISTRATION: ClinicalTrial.gov Identifier, https://clinicaltrials.gov/, NCT01808313 Registration date (first time): February 28, 2013.

Platelets enhance lymphocyte adhesion and infiltration into arterial thrombus.

Lymphocytes are present in atherosclerotic lesion. We hypothesise that platelets may facilitate lymphocyte infiltration into the arterial wall. Reconstituted human blood or whole blood was perfused through a collagen-coated parallel-plate flow chamber at different shear rates. Adhered platelets markedly enhanced lymphocyte adhesion that increased lymphocyte deposition from 10 ± 3 cells/mm2 of platelet-depleted blood to 38 ± 11 cells/mm2 of platelet-containing blood at the arterial shear rate of 500 s-1. Platelet-dependent lymphocyte adhesion was inhibited by P-selectin, CD40L, and GPIIb/IIIa-blocking agents, suggesting the involvement of multiple adhesion molecules in this heterotypic interaction. Lymphocyte deposition was more marked among T cells, and seen in both small and large cells. B and natural killer cell adhesion was, however, mainly seen in small cells. Platelet-conjugation facilitated lymphocyte adhesion, as suggested by the selective deposition of platelet-conjugated lymphocytes. In a mouse model of arterial thrombosis, FeCl3-induced thrombus formation markedly enhanced lymphocyte adhesion and infiltration into platelet thrombi, which was abolished by GPIIb/IIIa inhibition. In conclusion, platelets support lymphocyte adhesion under arterial flow conditions, which is selective among T cells and involves multiple adhesion molecules. Our data imply that platelets may facilitate the recruitment of circulating lymphocytes at the arterial injured sites.

Safety and efficacy of transcatheter closure of atrial septal defects guided by transthoracic echocardiography: a prospective study from two Chinese Medical Centers.

The purpose of this study was to evaluate the safety and efficacy of transcatheter atrial septal defect (ASD) closure guided by transthoracic echocardiography (TTE). A total of 191 patients with ASD were recruited from two Chinese medical centers and TTE was carefully performed in multiple views to observe ASD number, position, diameter and relation with adjacent cardiac structures. All patients were divided into three groups based on their largest ASD diameters: 66 subjects with ASD diameter 5-14 mm (group A); 60 subjects with ASD diameter 15-20 mm (group B); and 65 subjects with ASD diameter 21-38 mm (group C). Atrial septal occluders (ASOs) were successfully deployed in 188 patients (98.4%) and ASD was successfully closed at 6-mo follow-up in 185 patients (96.9%). The difference between diameters of ASO and ASD (ASO-ASD) in groups A, B and C were 3.9 +/- 2.4 (0-7) mm, 5.0 +/- 2.6 (3-8) mm and 6.2 +/- 3.8 (5-11) mm, respectively. In group A, no complications occurred. In group B, only four patients had mild complications such as sinus bradycardia, transient hematuria and migraine, all of which disappeared after treatment. In group C, one patient developed ASO migration into the right atrium and two patients had their ASO migrated into the right ventricular outflow tract. Immediately after the closure, 60 (90.9%), 53 (88.3%) and 53 (82.8%) patients had complete ASD closure; 2, 4 and 6 patients had trivial residual shunts; 4, 3 and 2 patients had small residual shunts; and 0, 0 and 2 patients had moderate residual shunts in groups A, B and C, respectively. Most of the residual shunts were persistent at 6-mo follow-up. No embolism or death at procedure and 6-mo follow-up occurred. In conclusion, TTE is a reliable technique for measurement of ASD diameter, guidance of transcatheter ASD closure and evaluation of residual shunts. Transcatheter ASD closure guided by TTE is safe and effective, especially in patients with ASD

Reliability of transthoracic echocardiography in estimating the size of Amplatzer septal occluder and guiding percutaneous closure of atrial septal defects.

BACKGROUND: In China, transthoracic echocardiography (TTE) is popularly used for pre-intervention examination for atrial septal defect (ASD) and for guiding ASD closure. However, the ability to determine ASD size and the safety and efficacy of TTE for guiding ASD closure still has not been widely accepted. This study aimed to evaluate the efficacy and safety of TTE used before, during and after transcatheter ASD closure with Amplatzer septal occluders (ASO). METHODS: Sixty-eight subjects (15 men and 53 women; mean age (33.7 +/- 17.3) years) were enrolled. TTE was used to measure the diameters and guide transcatheter closure of ASD. The ASD was examined by long-axis view, basal short-axis view, apical four-chamber view and the subcostal view to observe position, diameter and relation with neighbouring structures. The largest diameter was selected as the reference diameter. Patients were divided into 3 groups according to the ASD reference diameter: 22 subjects with ASD diameter 4 - 14 mm (group A); 21 subjects with ASD diameter 15 - 20 mm (group B); and 25 subjects with ASD diameter 21 - 33 mm (group C). RESULTS: ASD was occluded successfully in groups A and B. In group C, occlusion failed in 2 cases; 1 case remained with a 3-mm residual shunt sustained until 6-month follow-up. However, at 6-month follow-up, no case of thromboembolism, ASO dislocation or death occurred in the three groups. The diameter of ASD measured by TTE could accurately predict the ASO size that could successfully occlude the ASD, especially in patients with ASD < 20 mm. The ASD diameter measured by TTE correlated well with ASO size (r = 0.925, P < 0.001; r = 0.976, P < 0.001; r = 0.929, P < 0.001 respectively). CONCLUSIONS: ASD diameter measured by TTE can accurately estimate the size of the ASO needed for successful closure of ASD. The larger the ASD, the much larger the ASO needed. TTE is a satisfactory guiding imaging tool for ASD closure.

Multivessel percutaneous coronary intervention in Chinese patients with acute myocardial infarction and simple nonculprit arteries.

BACKGROUND: Multivessel percutaneous coronary intervention (PCI) for patients during acute myocardial infarction (AMI) is currently controversial. In this study, we investigated the significance of multivessel PCI in Chinese patients with ST-segment elevation AMI and relatively simple lesions in nonculprit arteries. METHODS: We reviewed all consecutive primary PCI of ST-segment elevation AMI in our hospital between 2002 and 2005. The patients with multivessel disease and ACC/AHA type A/B1 lesions in nonculprit arteries who underwent multivessel PCI were identified (n = 105, multivessel PCI group), and 120 patients with single-vessel disease and treatment with primary PCI were enrolled as control subjects (single-vessel PCI group). The primary end points were the occurrences of 6-month major adverse cardiac events (cardiogenic death, nonfatal reinfarction, and target vessel revascularization). The secondary end points included procedure time, angiographic success rate, TIMI grade, reperfusion arrhythmia, ST-segment resolution, and left ventricular ejection fraction. RESULTS: All patients with multivessel PCI tolerated the operations well and had similar TIMI 3 and angiographic success rates but longer procedure times than those patients with single-vessel PCI. There were no significant differences in reperfusion arrhythmia, ST-segment resolution, left ventricular ejection fraction, or 6-month MACEs between both groups. CONCLUSIONS: This study suggests that multivessel PCI is effective and safe for Chinese patients with ST-segment elevation AMI and simple lesions in nonculprit arteries.

Facilitated PCI in younger Chinese patients with AMI.

Presently, facilitated percutaneous coronary intervention (PCI) in patients remains controversial. We evaluated the efficacy and safety of facilitated PCI, intravenous low-dose rt-PA administration prior to urgent PCI, in Chinese patients < 70 years of age with ST-segment elevation myocardial infarction. Our results suggest that the age and dosage of thrombolytics should be noticed seriously when considering facilitated PCI.

[The role of atherosclerotic plaque stability and inflammation in the pathogenesis of acute coronary syndrome].

OBJECTIVE: To elucidate the effect of inflammation and coronary atherosclerotic plaque destabilization in the pathogenesis of acute coronary syndromes (ACS). METHODS: Twenty-eight patients with ACS and 13 patients with stable angina pectoris (SA) were examined by intravascular ultrasound (IVUS). Coronary plaque morphology and areas in culprit lesions were analyzed. The serum levels of hs-CRP, MMP-9, TIMP-1, sCD40L were also measured. RESULTS: Soft plaques were dominant in culprit lesions of ACS patients (71.4%, 20/28), and hard plaques were dominant in culprit lesions of SA patients [76.9% (10/13), P = 0.004]. At the culprit site, plaque area, plaque burden and remodeling index were all significantly larger in culprit lesions of ACS patients than those of SA patients (all P < 0.05). Positive remodeling was more frequent in ACS patients than in SA patients, whereas negative remodeling was more frequent in SA patients (P < 0.05). The serum levels of hs-CRP, MMP-9, sCD40L were higher in ACS group compared with SA group (P < 0.05, respectively). Moreover, hs-CRP level was positively correlated with MMP-9 (r = 0.671, P = 0.000) and sCD40L (r = 0.494, P = 0.008), respectively, in ACS patients. There was no difference in TIMP-1 between two groups (P = 0.234). CONCLUSIONS: These results suggest that structurally vulnerable plaques are essential element in the pathogenesis of ACS and inflammation might play an important role in plaque vulnerability.

High glucose levels enhance platelet activation: involvement of multiple mechanisms.

Diabetes mellitus (DM) and hyperglycaemia are associated with platelet activation. The present study was designed to investigate how high glucose levels influence platelet function. Fasting human blood was incubated with different concentrations of D-glucose (5, 15 and 30 mmol/l) and other sugars without or with in vitro stimuli. Platelet activation was monitored by whole blood flow cytometry. High glucose levels enhanced adenosine diphosphate (ADP)- and thrombin receptor-activating peptide (TRAP)-induced platelet P-selectin expression, and TRAP-induced platelet fibrinogen binding. Similar effects were seen with 30 mmol/l L-glucose, sucrose and galactose. Hyperglycaemia also increased TRAP-induced platelet-leucocyte aggregation. Protein kinase C (PKC) blockade did not counteract the enhancement of platelet P-selectin expression, but abolished the enhancement of TRAP-induced platelet fibrinogen binding by hyperglycaemia. Superoxide anion scavenging by superoxide dismutase (SOD) attenuated the hyperglycaemic enhancement of platelet P-selectin expression, but did not counteract the enhancement of TRAP-induced platelet fibrinogen binding. Hyperglycaemia did not alter platelet intracellular calcium responses to agonist stimulation. Blockade of cyclo-oxygenase (COX), phosphotidylinositol-3 (PI3) kinase, or nitric oxide synthase, or the addition of insulin did not influence the effect of hyperglycaemia. In conclusion, high glucose levels enhanced platelet reactivity to agonist stimulation through elevated osmolality. This occurred via superoxide anion production, which enhanced platelet P-selectin expression (secretion), and PKC signalling, which enhanced TRAP-induced fibrinogen binding (aggregablity).

Effect of aspirin plus clopidogrel on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: One hundred and fifteen patients with NSTEACS were randomized into two groups: group A (aspirin alone, n =58) and group B (aspirin plus clopidogrel, n =57). Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha) were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls (group C). RESULTS: Baseline levels of hs-CRP and TNF-alpha in group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A: (6.15 +/- 1.39) mg/L vs (9.18 +/- 1.62) mg/L, P <0.01; Group B:(4.99 +/- 1.62) mg/L vs (10.29 +/- 1.47) mg/L, P <0.01]. Similarly, levels of TNF- alpha in both groups decreased at 7 days compared to baseline [Group A: (90.99 +/- 28.91) pg/ml vs (117.20 +/- 37.13) pg/ml, P <0.01; Group B: (74.32 +/- 21.83) pg/ml vs (115.27 +/- 32.11) pg/ml, P <0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to (3.49 +/- 1.53) mg/L, and (2.40 +/- 1.17) mg/L respectively (P <0.01 for both comparisons). Levels of TNF-alpha in groups A and B also decreased significantly between 7 and 30 days, to 63.28 +/- 29.01 pg/ml (group A) and (43.95 +/- 17.10) pg/ml (group B; P <0.01 for both comparisons). Significantly lower levels of hs-CRP and TNF-alpha were observed in group B compared to Group A at thirty days after initiating drug treatment (P <0.05). CONCLUSIONS: Aspirin plus clopidogrel treatment reduced levels of serum hs-CRP and TNF-alpha in patients with NSTEACS significantly more than aspirin alone. Because both aspirin and clopidogrel produce important anti-inflammatory effects, these results suggest the possibility that long-term treatment with aspirin plus clopidogrel may produce greater clinical benefits compared to treatment with aspirin alone.

Contrast medium attenuates platelet activation and platelet-leukocyte cross-talk.

The influence of ionic and non-ionic contrast media (CM) on platelet and leukocyte activation and platelet-leukocyte crosstalk was investigated in hirudinized whole blood. The blood was incubated with and without the ionic CM ioxaglate and the nonionic CM iodixanol at 37 degrees C for 5 min, without or with stirring. Platelet and leukocyte activation and platelet-leukocyte aggregation were measured using whole blood flow cytometry. When blood samples were pre-incubated in the presence of 2%, 5%, and 10% of CM without stirring, both ioxaglate and iodixanol had little effect on unstimulated samples, but dose-independently decreased 1 microM ADP-induced platelet P-selectin expression and fibrinogen binding, and thus platelet-leukocyte aggregate formation. Ioxaglate had little effect on leukocyte CD11b expression, whilst iodixanol slightly enhanced resting and N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1 microM)-stimulated leukocyte CD11b expression. Blood samples were also incubated with stirring to investigate the impact of CM (5% of ioxaglate or iodixanol) on platelet-leukocyte cross-talk. Collagen induced marked platelet activation and platelet-leukocyte aggregation, and subsequently elevated leukocyte CD11b expression. The latter was attenuated by ioxaglate and iodixanol, and was accompanied by reduced platelet-leukocyte aggregation. In conclusion, the CM ioxaglate and iodixanol attenuate platelet activation and platelet-leukocyte cross-talk. Inhibitory effects of the contrast agents on this cross-talk are apparently exerted by reducing heterotypic conjugation, and may be beneficial in connection with PCI.