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1.
Blood ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481482

RESUMO

Clinical observations implicate a role of eosinophils in cardiovascular diseases, because markers of eosinophils activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cell and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo identifying this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31504375

RESUMO

AIMS: Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events remains controversial. METHODS AND RESULTS: We assessed the impact of 31 candidate gene polymorphisms on ADP-stimulated platelet reactivity in 3,391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on cardiovascular events (CVE) was tested in 2,134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8x10-54; CES1 G143E, P = 1.3x10-16; CYP2C19*17, P = 9.5x10-10; CYP2B6 1294 + 53C>T, P = 3.0x10-4; CYP2B6 516G>T, P = 1.0x10-3; CYP2C9*2, P = 1.2x10-3; and CYP2C9*3, P = 1.5x10-3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (ß = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (ß = 0.43, SE 0.16, P = 0.007). Patients who carried 8 or more risk alleles were significantly more likely to experience CVEs (OR = 1.78, 95%CI 1.14-2.76, P = 0.01) and cardiovascular death (OR = 4.39, 95%CI 1.35-14.27, P = 0.01) compared to patients who carried 6 or fewer of these alleles. CONCLUSION: Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.

3.
N Engl J Med ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479209

RESUMO

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).

4.
Am J Cardiol ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31443900

RESUMO

A new collagen-based MANTA vascular closure device (VCD) was developed for closing large-bore arteriotomies after transfemoral transcatheter aortic valve implantation (TAVI). We evaluated safety and feasibility at 30-day follow-up in terms of vascular and bleeding complications and mortality of the collagen-based MANTA VCD compared with the suture-based Prostar XL VCD in a cohort of 366 patients who underwent transfemoral TAVI between January 2015 and April 2018. The MANTA VCD was used in 168 patients and the Prostar XL VCD in 198 patients, with successful closure of 98.8% and 98.5%, respectively. VARC-2 defined as major vascular and bleeding complications was similar in both groups (MANTA vs Prostar XL): 0.6% versus 1.0% (p = 0.661) and 0.6% versus 1.5% (p = 0.102). Minor vascular and bleeding complications, were significantly more frequent (10.7 vs 18.8 %, p = 0.003 and 13.7 vs 19.7%, p = 0.080, respectively) in the Prostar XL cohort. Thirty-day all-cause mortality was 2.7%, without significant difference between the groups (p = 0.278). The MANTA device is a safe and feasible option for vascular access closure in patients undergoing transfemoral TAVI.

5.
JACC Cardiovasc Interv ; 12(16): 1553-1561, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31439336

RESUMO

OBJECTIVES: The study sought to evaluate the effect of dabigatran dual therapy versus warfarin triple therapy across categories of renal function in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy with Dabigatran versus Triple Therapy with Warfarin in Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial. BACKGROUND: The RE-DUAL PCI (NCT02164864) trial of patients with atrial fibrillation undergoing percutaneous coronary intervention reported that dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) reduced the primary endpoint of major bleeding events (MBE) or clinically relevant nonmajor bleeding events (CRNMBE) compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. METHODS: Risk of a first MBE or CRNMBE and the composite of death or thromboembolic event (DTE) or unplanned revascularization were evaluated in 2,725 patients according to baseline creatinine clearance (CrCl) categories: 30 to <50, 50 to <80, and ≥80 ml/min. RESULTS: Compared with warfarin, dabigatran 110 mg dual therapy reduced risk of MBE or CRNMBE across all categories of CrCl (p for interaction = 0.19). Dabigatran 150 mg dual therapy reduced risk of MBE or CRNMBE regardless of the CrCl category (p for interaction = 0.31). Risk of DTE or unplanned revascularization was similar to warfarin triple therapy for dabigatran 110 mg dual therapy across all CrCl categories. Dabigatran 150 mg dual therapy versus warfarin triple therapy had similar risk for DTE or unplanned revascularization in patients with CrCl 30 to <80 ml/min and lower risk at CrCl ≥80 ml/min (p for interaction = 0.02). CONCLUSIONS: In the RE-DUAL PCI trial, dabigatran dual therapy reduced bleeding events versus warfarin triple therapy irrespective of renal function, with overall similar risks of thromboembolic events but lower risks with dabigatran 150 mg in patients with normal CrCl.

8.
Blood Coagul Fibrinolysis ; 30(6): 263-269, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31259779

RESUMO

: High on-treatment platelet reactivity (HPR) on P2Y12-inhibitors in patients treated with dual antiplatelet therapy is strongly associated with adverse ischaemic events. Studies have shown conflicting results with regard to the correlation and agreement between the different tests. Several assays are available to establish HPR. A composite advice based on more than one test might be a better way to identify HPR patients. To compare HPR rates and agreement between individual platelet function tests and a panel of three tests In our large percutaneous coronary intervention centre, all patients who suffered a stent thrombosis were invited back to a dedicated clinic. Platelet function testing was performed in all patients and matched control patients. HPR rates were compared between individual tests and with a composite comprised of three tests. A total of 242 patients were included, of whom in 193 patients all tests were available. HPR rates ranged from 14.6% [VerifyNow cut-off >235 platelet reactivity units (PRU)] to 49.7% (Vasodilator-Stimulated Phosphoprotein Assay). HPR according to the composite advice (≥2 out of 3 tests indicating HPR) was present in 29.8% of patients. The best correlation with the composite advice was observed with light transmittance aggregometry (kappa = 0.78) and VerifyNow (lower cut-off >208 PRU; kappa = 0.68). VerifyNow with cut-off more than 235 PRU identified the smallest proportion of patients with HPR, whereas Vasodilator-Stimulated Phosphoprotein Assay seemed to 'over-identify' HPR. In this real life patient cohort, a large variability was observed between four different platelet function tests. The use of a composite advice based on three tests is a promising alternative.

9.
J Am Coll Cardiol ; 74(5): 699-711, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31277840

RESUMO

For secondary prevention of coronary artery disease (CAD), oral antiplatelet therapy is essential. In case of coronary intervention, temporary dual antiplatelet therapy is mandatory as well. Recently, low-dose oral anticoagulation has entered the CAD arena. Atrial fibrillation (AF) is often seen in CAD and vice versa. In most patients stroke prevention in AF consists of oral anticoagulation. In many cases of CAD in patients with AF, anticoagulation has to be combined with antiplatelet agents (so called, dual pathway antithrombotic therapy). Excess bleeding in these conditions is a rapidly rising problem. This review addresses the antithrombotic options in CAD alone, in AF alone, and in their combination, when either an invasive or a noninvasive approach has been chosen.

10.
JAMA Cardiol ; 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215979

RESUMO

Importance: The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice. Objective: To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population. Data Sources: PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens. Study Selection: Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS). Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019. Main Outcomes and Measures: The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE. Results: The overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT. Conclusions and Relevance: A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post-percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.

11.
Eur J Clin Pharmacol ; 75(9): 1201-1210, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197411

RESUMO

PURPOSE: The POPular Risk Score was developed for the selective intensification of P2Y12 inhibitor treatment with prasugrel instead of clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI) with stent implantation. This score is based on platelet reactivity (VerifyNow P2Y12 assay), CYP2C19 genotyping, and clinical risk factors. Our aim was to determine if the use of this score in clinical practice is associated with a reduction in thrombotic events without increasing bleeding events. METHODS: In a single-center prospective cohort study, patients with a high risk score were treated with prasugrel and patients with a low risk score with clopidogrel. The risk score-guided cohort was compared with a historic cohort of clopidogrel-treated patients. The endpoint consisted of all-cause death, myocardial infarction, stroke, or stent thrombosis during 1 year of follow-up. TIMI major and minor bleeding events were also analyzed. RESULTS: The guided cohort contained 1127 patients, 26.9% of whom were switched to prasugrel according to the POPular Risk Score. The historic cohort contained 893 patients. The incidence of the combined thrombotic endpoint was significantly lower in the guided cohort as compared with the historic cohort (8.4% versus 3.7%, p < 0.001). This strategy was safe with respect to bleeding (4.0% versus 1.3%, p < 0.001, for TIMI major or minor bleeding). Results were comparable after multivariate and propensity score matched and weighted analysis. CONCLUSION: Selective intensification of P2Y12 inhibitor treatment after non-urgent PCI based on the POPular Risk Score is associated with a reduction in thrombotic events without an increase in bleeding events.

12.
Catheter Cardiovasc Interv ; 93(7): 1374-1381, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116908

RESUMO

BACKGROUND/OBJECTIVE: Prostar XL (PS) and ProGlide (PG) are common vascular closure devices (VCD) used in TAVR via transfemoral vascular approach. The impact of these VCD on vascular and bleeding complications remains unclear. METHODS: The BRAVO-3 trial randomized 802 patients undergoing transfemoral TAVR. We stratified patients according to type of VCD used and examined the 30-day incidence of major or minor vascular complications, major bleeding (BARC ≥3b), AKI and major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction or stroke). RESULTS: A total of 746 (93%) patients were treated with either PS (n = 352, 47%) or PG (n = 394, 53%) VCD, without significant differences in successful deployment rate (PS 322 [91.2%] vs. PG 373 [94.2%] respectively, p = .20). PG was associated with a significantly lower incidence of major or minor vascular complications, compared to PS (adjusted OR: 0.54; 95% CI: 0.37-0.80; p < .01). Rates of acute kidney injury were also lower with the PG device. There was no significant difference between bleeding, MACCE, and death. CONCLUSIONS: Compared to PS, the PG VCD was associated with a lower rate of major or minor vascular complications and lower rates of AKI after transfemoral TAVR.

13.
Perfusion ; 34(7): 613-617, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31027458

RESUMO

INTRODUCTION: Surgery for infective endocarditis imposes great challenges in post-operative circulatory and pulmonary support but the role of veno-arterial extra-corporal membrane oxygenation in this respect is unclear. METHODS: All patients undergoing veno-arterial extra-corporal membrane oxygenation after infective endocarditis surgery were analysed for age, gender, medical history, microorganisms, clinical outcome, complications and surgical procedure. RESULTS: Between 2012 and 2016, 13 patients received veno-arterial extra-corporal membrane oxygenation following infective endocarditis surgery. The median age was 62 years (33-73) and 8/13 were male. Previous cardiac surgery was present in nine patients. Surgery for infective endocarditis consisted of a Bentall procedure in 10 patients, 2 of which received concomitant mitral valve surgery and 2 received concomitant coronary artery bypass graft. Valvular surgery alone was performed in three patients. Mortality on veno-arterial extra-corporal membrane oxygenation was 62% (8/13). Mortality during intensive care unit stay was 77% (10/13). Survival to discharge was 23% (3/13). One patient reached the 1 year survival point. Two patients who survived to discharge have not yet reached the 1 year survival point. Patient-related complications occurred in 54% (7/13) of patients and consisted of haemorrhage at the cannula site in four patients, leg ischaemia in one patient, haemorrhage at another site in one patient and infection of the cannula in one patient. Extra-corporal membrane oxygenation hardware-related complications occurred in one case consisting of clot formation in the oxygenator. CONCLUSION: Veno-arterial extra-corporal membrane oxygenation in post-cardiotomy patients who were operated on for infective endocarditis is feasible, but outcome is poor.

14.
Am Heart J ; 212: 13-22, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928824

RESUMO

BACKGROUND: In the RE-DUAL PCI trial of patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI), dabigatran dual therapy (110 or 150 mg bid, plus clopidogrel or ticagrelor) reduced International Society on Thrombosis and Haemostasis bleeding events compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. This analysis assessed outcomes in relation to patient bleeding and stroke risk profiles, based on the modified HAS-BLED and CHA2DS2-VASc scores. METHODS: The primary endpoint, major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE), was compared across study arms in patients categorized by modified HAS-BLED score 0-2 or ≥3. The composite endpoint of death, thromboembolic event, and unplanned revascularization rates was compared in patients categorized by CHA2DS2-VASc score 0-1, 2, or ≥3. RESULTS: Risk of MBE or CRNMBE was lower with dabigatran dual therapy (both doses) versus warfarin triple therapy, irrespective of modified HAS-BLED category (treatment-by-subgroup interaction P-value 0.584 and 0.273 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Risk of the composite thromboembolic endpoint was similar across CHA2DS2-VASc categories and consistent with overall study results (interaction P-value 0.739 and 0.075 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Higher HAS-BLED scores were associated with higher risks of bleeding in AF patients after PCI in a treatment-independent analysis. CONCLUSION: Dabigatran dual therapy reduced bleeding events irrespective of bleeding risk category and demonstrated similar efficacy regardless of stroke risk category when compared with warfarin triple therapy.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30919577

RESUMO

BACKGROUND: Percutaneous recanalization of coronary chronic total occlusions (CTOs) traditionally relies on the use of dual-access and large bore catheters, with trans-femoral approach adoption in most cases. OBJECTIVES: Aim of this manuscript is to describe the outcomes of an alternative hybrid algorithm, called "Minimalistic Hybrid Algorithm," which has the purpose to minimize the use of double access, large bore catheters, and femoral approach in order to minimize the risk of vascular complications and patient's discomfort, without compromising efficacy. METHODS: In this single-center registry, a "minimalistic" approach was attempted in consecutive patients undergoing CTO PCI between March 2016 and October 2017. Data regarding the applicability of this algorithm and the related procedural success rates were collected, together with common demographic and angiographic characteristics. RESULTS: Of the 100 CTO PCI performed in the study period, 91(91%) were successfully approached according to the novel algorithm. Mean J-CTO score of all minimalistic procedures was 1.9 ± 1.2, with 31(34%) patients presenting with J-CTO score ≥3. In 52 procedures, the approach consisted of single-catheter access, 49(94.2%) of which were trans-radial. Out of the 39 patients approached with dual-catheters, 26(69.2%) were biradial, and 8(21%) radial-femoral. Procedural success in patients approached with the minimalistic algorithm was 89%, in line with the results of large-multicenter experiences nowadays available. CONCLUSIONS: Our results show that an alternative algorithm limiting the routine use of large bore catheters and trans-femoral approach is feasible in the clinical practice and yields good procedural outcomes.

16.
Eur Heart J ; 40(19): 1553-1562, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30793734

RESUMO

AIMS: After percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment. METHODS AND RESULTS: In the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35-0.63) for 110 mg and 0.67 (0.50-0.90) for 150 mg]; elective PCI [0.57 (0.43-0.76) for 110 mg and 0.76 (0.56-1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28-0.76) for 110 mg and 0.59 (0.34-1.04) for 150 mg]; or clopidogrel [0.51 (0.41-0.64) for 110 mg and 0.73 (0.58-0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10. CONCLUSION: The benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.

17.
Cardiovasc Res ; 115(10): 1512-1518, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768153

RESUMO

AIM: A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. METHODS AND RESULTS: The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU⋅min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203 AU⋅min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. CONCLUSION: We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.

18.
Catheter Cardiovasc Interv ; 93(5): E293-E297, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30585388

RESUMO

OBJECTIVES: To investigate the potential association between early tirofiban treatment and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level after primary percutaneous coronary intervention (PCI). BACKGROUND: Whether the use of adjunctive early glycoprotein IIb/IIIa inhibitors (GPIs) therapy, may affect the level of NT-proBNP after primary PCI is poorly studied. METHODS: Nine hundred and eighty four ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI were randomized to either pre-hospital tirofiban administration or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hr after PCI. RESULTS: There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post-PCI. Post-PCI NT-proBNP level dichotomized with median value as cut-off (968.8 pg/mL, IQR 430.9-1970.0) was significantly lower in patients treated with early tirofiban as compared to placebo (45.5% vs. 54.2% P = 0.011). At multivariate logistic regression analysis, independent predictors of post-PCI NT-proBNP level above the median were: NT-proBNP baseline level (OR 5.19; 95% CI, 2.92-9.25, P < 0.001), Killip class>I (OR 4.07; 95% CI 1.24-13.36, P = 0.021), anterior infarct location (OR 2.61; 95% CI 1.84-3.70, P < 0.001), age (years) (OR 1.04; 95% CI 1.03-1.06, P < 0.001), male gender (OR 0.38; 95% CI 0.26-0.57, P < 0.001), prior PCI (OR 0.49; 95% CI 0.27-0.90, P = 0.021) and tirofiban administration (OR 0.71; 95% CI 0.51-0.99; P = 0.045). CONCLUSIONS: In a large cohort of STEMI patients, pre-hospital tirofiban administration was independently associate with a lower risk of high NT-proBNP level after primary PCI, supporting the potential benefit of early antithrombotic treatment administration in STEMI patients. The trial is registered under No. ISRCTN06195297.

19.
Artigo em Inglês | MEDLINE | ID: mdl-30461175

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of the Occlutech patent foramen ovale (PFO) device at long-term follow-up (FU). BACKGROUND: The Occlutech device has been proven safe and effective six-months after percutaneous PFO closure. We describe the safety and efficacy after more than 1,300 patient-years of FU. METHODS: All consecutive patients who underwent PFO closure between October 2008 and December 2015 were included. All complications were registered. Residual right-to-left shunt (RLS) was diagnosed using contrast transthoracic echocardiography and graded as minimal, moderate, or severe. RESULTS: In total, 250 patients (mean age 53.5 ± 10.7 years, 46.8% female) underwent percutaneous PFO closure using the Occlutech device. Mean FU was 5.9 ± 1.8 years, a total of 1,345 patient-years. Transient ischemic attack (TIA) or stroke was the main indication for closure (89.6%). Implantation was successful in 100%, no major complications occurred. Minor complications were inguinal hematoma in 16 patients (6.4%), pericardial effusion without the need for intervention in one patient (0.4%) and a supraventricular tachycardia in one patient (0.4%). A moderate or large shunt at one-year follow up was present in 5.9%. A cerebrovascular vascular event occurred in 2.0% at 1-year FU (four TIA, one stroke) and in 7.4% at long-term FU (nine TIA, eight stroke). The total cerebrovascular event rate (TIA and CVA) was 0.02% per patient-year of FU, with a stroke rate of 0.01%. CONCLUSION: The Occlutech device appears to be safe at long-term FU with a very low annual cerebrovascular event rate and a low moderate to large shunt rate at 1-year FU.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30461187

RESUMO

OBJECTIVE: The aim of this study was to describe the early use of dedicated patient specific computer modeling in patients with bicuspid aortic valve (BAV) undergoing transcatheter aortic valve implantation (TAVI), in predicting procedure feasibility and patient related outcome. BACKGROUND: Dedicated patient specific computer modeling, used for optimizing TAVI procedures, is currently validated for the prediction of contact pressure, valve morphology and paravalvular leakage (PVL). The simulation of TAVI procedures is increasingly used in patients with tricuspid aortic valve stenosis. Currently, BAV disease is considered as a relative contra-indication for TAVI due to its specific anatomical characteristics. METHODS: This single center study consisted of seven patients with BAV undergoing TAVI. A patient specific computer simulation was performed based on multislice computer tomography images. The model advised the best fitting prosthetic valve size or sizes and simulated this valve on different implantation depths with the corresponding presence and severity of PVL and prosthetic valve morphology. The simulation results were compared with the procedural outcomes using transesophageal echocardiography (TEE) and fluoroscopy. RESULTS: The patient specific computer modeling predicted accurately the outcome (PVL and valve morphology) of TAVI in all cases. In one case, the TAVI procedure was unsuccessful and retrospectively not suitable for TAVI, which was correctly predicted by the model. CONCLUSION: The patient specific computer modeling adequately predicts feasibility and outcome of TAVI in patients with BAV disease and may extend the applicability of TAVI. Moreover, it improves decision-making and therefore individual procedural outcomes in this difficult patient population.

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