Antiplatelet and anticoagulant therapy after coronary-artery stenting

To the Editor: Schömig et al. (April 25 issue) report that they did not observe neutropenia in any of the 257 patients receiving short-term ticlopidine therapy after coronary stenting

Can the vicious cycle of obscure or intractable gastrointestinal bleeding be broken in patients with atrial fibrillation subject to anticoagulant therapy? The role of percutaneous left atrial appendage closure

Gastrointestinal bleeding of obscure origin or with an intractable cause is particularly common in patients with atrial fibrillation subject to oral anticoagulant therapy. This condition is highly recurrent and therefore gives rise to high morbidity and mortality rates, thus entailing a vicious cycle that is difficult to solve.Percutaneous left atrial appendage closure has become a therapeutic alternative for patients with atrial fibrillation and a contraindication for oral anticoagulation. This technique would allow the discontinuation of oral anticoagulants, thus helping to reduce the risk for gastrointestinal bleeding, and would also be protective against embolic events in this group of patients, thereby eventually breaking this vicious cycle.We report our experience with percutaneous left atrial appendage closure in the management of patients with atrial fibrillation who are subject to oral anticoagulation therapy and suffer from obscure or intractable gastrointestinal bleeding

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported. Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death. Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coronary artery disease), diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to one year v longer duration treatment with dual antiplatelets. Conclusions: This meta-analysis offers evidence that compared with bare metal stents the use of cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes including cardiac survival, myocardial infarction, and overall stent thrombosis

Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis

Despite the promising value of miRNAs in the diagnostic and prognostic of cardiovascular disease (CVD), recent meta-analyses did not support their potential. Methodological variances in studies may interfere with miRNA profle and afect their results. This study determines if the blood starting material is a source of variance in miRNA profle by performing a paired comparison in plasma and serum of the expression of primary miRNAs associated with CVD. Circulating miRNA yield was similar in both plasma and serum, although a signifcant increase was observed in patients with Non-ST-elevation myocardial infarction (NSTEMI) compared to control volunteers. When normalized by the expression of miR-484, diferent patterns of miRNA expression between serum and plasma. Although NSTEMI modifed the expression of miR-1 and miR-208 in both serum and plasma, plasma displayed a higher variance than serum (Levene's test p<0.01). For miR-133a and miR-26a, diferences were only detected in serum (p=0.0240), and conversely, miR-499a showed diferences only in plasma of NSTEMI (p=0.001). Interestingly, miR-21 showed an opposite pattern of expression, being increased in serum (2−ΔΔCt : 5.7, p=0.0221) and decreased in plasma (2−ΔΔCt : 0.5, p=0.0107). Plasma and serum exhibit diferent patterns of circulating miRNA expression in NSTEMI and suggest that results from studies with diferent starting material could not be comparable

Direct actions of dapagliflozin and interactions with LCZ696 and spironolactone on cardiac fibroblasts of patients with heart failure and reduced ejection fraction

Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF).Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM-1 ?M) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound-healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers [fold-change (Log2): COL1A1-1.3; IL-1b-1.9; IL-6-1.7; FN1-2.9 (P < 0.05)]. Dapagliflozin slowed the migration rate of HFrEF fibroblasts in a dose-dependent manner and markedly decreased the expression of IL-1?, IL-6, MMP3, MMP9, GAL3, and FN1. SGLT2i had no effect on control fibroblasts. These effects were associated with decreased phosphorylation of AKT/GSK3 and PYK2 kinases and the signal transducer and activator of transcription (STAT). A combination of dapagliflozin + LCZ696 further decreased fibroblast migration, although it did not have a significant effect on the regulation of signalling pathways and the expression of biomarkers induced by SGLT2 inhibition alone. In contrast, the combination of dapagliflozin + spironolactone did not change the migration rate of fibroblast but significantly altered SGLT2i responses on MMP9, GAL3, and IL-1b expression, in association with increased phosphorylation of the kinases AKT/GSK3 and ERK1/2.SGLT2i, LCZ696, and spironolactone modulate the function of isolated myocardial fibroblasts from HFrEF patients through the activation of different signalling pathways. The combination of SGLT2i + LCZ696 shows an additive effect on migration, while spironolactone modifies the signalling pathways activated by SGLT2i and its beneficial effects of biomarkers of heart failure.© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology

Cost-effectiveness of everolimus-eluting versus bare-metal stents in ST-segment elevation myocardial infarction: An analysis from the EXAMINATION randomized controlled trial.

BACKGROUND: Use of everolimus-eluting stents (EES) has proven to be clinically effective and safe in patients with ST-segment elevation myocardial infarction but it remains unclear whether it is cost-effective compared to bare-metal stents (BMS) in the long-term. We sought to assess the cost-effectiveness of EES versus BMS based on the 5-year results of the EXAMINATION trial, from a Spanish health service perspective. METHODS: Decision analysis of the use of EES versus BMS was based on the patient-level clinical outcome data of the EXAMINATION trial. The analysis adopted a lifelong time horizon, assuming that long-term survival was independent of the initial treatment strategy after the end of follow-up. Life-expectancy, health-state utility scores and unit costs were extracted from published literature and publicly available sources. Non-parametric bootstrapping was combined with probabilistic sensitivity analysis to co-assess the impact of patient-level variation and parameter uncertainty. The main outcomes were total costs and quality-adjusted life-years. The incremental cost-effectiveness ratio was expressed as cost per quality-adjusted life-years gained. Costs and effects were discounted at 3%. RESULTS: The model predicted an average survival time in patients receiving EES and BMS of 10.52 and 10.38 undiscounted years, respectively. Over the life-long time horizon, the EES strategy was ¿430 more costly than BMS (¿8,305 vs. ¿7,874), but went along with incremental gains of 0.10 quality-adjusted life-years. This resulted in an average incremental cost-effectiveness ratio over all simulations of ¿3,948 per quality-adjusted life-years gained and was below a willingness-to-pay threshold of ¿25,000 per quality-adjusted life-years gained in 86.9% of simulation runs. CONCLUSIONS: Despite higher total costs relative to BMS, EES appeared to be a cost-effective therapy for ST-segment elevation myocardial infarction patients due to their incremental effectiveness. Predicted incremental cost-effectiveness ratios were below generally acceptable threshold values

Cost-effectiveness of a European ST-segment elevation myocardial infarction network: results from the Catalan Codi Infart network

Objectives: To evaluate the cost-effectiveness of the ST-segment elevation myocardial infarction (STEMI) network of Catalonia (Codi Infart). Design Cost-utility analysis. Setting: The analysis was from the Catalonian Autonomous Community in Spain, with a population of about 7.5 million people. Participants: Patients with STEMI treated within the autonomous community of Catalonia (Spain) included in the IAM CAT II-IV and Codi Infart registries. Outcome measures costs included hospitalisation, procedures and additional personnel and were obtained according to the reperfusion strategy. Clinical outcomes were defined as 30-day avoided mortality and quality-adjusted life-years (QALYs), before (N=356) and after network implementation (N=2140). Results: A substitution effect and a technology effect were observed; aggregate costs increased by 2.6%. The substitution effect resulted from increased use of primary coronary angioplasty, a relatively expensive procedure and a decrease in fibrinolysis. Primary coronary angioplasty increased from 31% to 89% with the network, and fibrinolysis decreased from 37% to 3%. Rescue coronary angioplasty declined from 11% to 4%, and no reperfusion from 21% to 4%. The technological effect was related to improvements in the percutaneous coronary intervention procedure that increased efficiency, reducing the average length of the hospital stay. Mean costs per patient decreased from 8306 to 7874 for patients with primary coronary angioplasty. Clinical outcomes in patients treated with primary coronary angioplasty did not change significantly, although 30-day mortality decreased from 7.5% to 5.6%. The incremental cost-effectiveness ratio resulted in an extra cost of 4355 per life saved (30-day mortality) and 495 per QALY. Below a cost threshold of 30,000, results were sensitive to variations in costs and outcomes. Conclusions: The Catalan STEMI network (Codi Infart) is cost-efficient. Further studies are needed in geopolitical different scenarios

Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function, in a translational model of acute myocardial infarction

Background-¿Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. Methods and Results-¿Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6 6% versus 55.9 5.7% in vehicle; P=0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1a gene expression; and increased M2 macrophages (67.2 10% versus 54.7 10.2% in vehicle; P=0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9 28.7 versus 57.4 17.7 mL/min per gram at 7 days; P=0.034 and 99 22.6 versus 43.3 14.7 22.6 mL/min per gram at 60 days; P=0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118 18 versus 92.4 24.3 vessels/mm2 in vehicle; P=0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. Conclusions-¿In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. No effect on left ventricular volumes or ejection fraction was observed

Can the vicious cycle of obscure or intractable gastrointestinal bleeding be broken in patients with atrial fibrillation subject to anticoagulant therapy? The role of percutaneous left atrial appendage closure

Gastrointestinal bleeding of obscure origin or with an intractable cause is particularly common in patients with atrial fibrillation subject to oral anticoagulant therapy. This condition is highly recurrent and therefore gives rise to high morbidity and mortality rates, thus entailing a vicious cycle that is difficult to solve.Percutaneous left atrial appendage closure has become a therapeutic alternative for patients with atrial fibrillation and a contraindication for oral anticoagulation. This technique would allow the discontinuation of oral anticoagulants, thus helping to reduce the risk for gastrointestinal bleeding, and would also be protective against embolic events in this group of patients, thereby eventually breaking this vicious cycle.We report our experience with percutaneous left atrial appendage closure in the management of patients with atrial fibrillation who are subject to oral anticoagulation therapy and suffer from obscure or intractable gastrointestinal bleeding

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported. Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death. Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coronary artery disease), diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to one year v longer duration treatment with dual antiplatelets. Conclusions: This meta-analysis offers evidence that compared with bare metal stents the use of cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes including cardiac survival, myocardial infarction, and overall stent thrombosis