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1.
Front Cardiovasc Med ; 10: 1219589, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727302

RESUMO

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

2.
J Thromb Thrombolysis ; 56(4): 499-510, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37563502

RESUMO

Understanding the pharmacodynamic effects of platelet inhibitors is standard for developing more effective antithrombotic therapies. An example is the antithrombotic treatment of acute coronary syndrome (ACS), in particular ST-elevated myocardial infarction (STEMI) patients who are in need for rapid acting strong antithrombotic therapy despite the use of aspirin and oral P2Y12-inhibitors. In this study, we evaluated two injectable platelet inhibitors under clinical development (the P2Y12 antagonist selatogrel and the GPIIb-IIIa antagonist zalunfiban) that may be amenable to pre-hospital treatment of STEMI patients. Platelet reactivity was assessed at inhibitor concentrations that represent clinically relevant levels of platelet inhibition (IC20-50%, 1/2Cmax, and Cmax). Light transmission aggregometry (LTA), was used to evaluate the initial rate of aggregation (primary slope, PS) and maximal aggregation (MA). Both adenosine diphosphate (ADP) and thrombin receptor agonist peptide (TRAP) were used as agonists. Zalunfiban demonstrated similar inhibition of platelet aggregation when blood was collected in PPACK or TSC, whereas selatogrel demonstrated greater inhibition in PPACK. In this study, using PPACK anticoagulant, selatogrel and zalunfiban affected PS in response to ADP equivalently at all drug concentrations tested. In contrast, zalunfiban had significantly greater potency at its Cmax concentration compared to selatogrel using TRAP as agonist. Upon evaluation of MA responses at lower doses, selatogrel had greater inhibition of MA in response to ADP than zalunfiban; however, at concentrations that represent Cmax, the drugs were equivalent. Zalunfiban also had greater inhibition of MA in response to TRAP at the Cmax dose. These data suggest that zalunfiban may provide greater protection in reducing thrombus formation than selatogrel, especially since thrombin is an early, key primary agonist in the pathophysiology of thrombotic events.

4.
Eur Heart J ; 44(2): 100-112, 2023 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-36337034

RESUMO

The use of biomarkers is undisputed in the diagnosis of primary myocardial infarction (MI), but their value for identifying MI is less well studied in the postoperative phase following coronary artery bypass grafting (CABG). To identify patients with periprocedural MI (PMI), several conflicting definitions of PMI have been proposed, relying either on cardiac troponin (cTn) or the MB isoenzyme of creatine kinase, with or without supporting evidence of ischaemia. However, CABG inherently induces the release of cardiac biomarkers, as reflected by significant cTn concentrations in patients with uncomplicated postoperative courses. Still, the underlying (patho)physiological release mechanisms of cTn are incompletely understood, complicating adequate interpretation of postoperative increases in cTn concentrations. Therefore, the aim of the current review is to present these potential underlying mechanisms of cTn release in general, and following CABG in particular (Graphical Abstract). Based on these mechanisms, dissimilarities in the release of cTnI and cTnT are discussed, with potentially important implications for clinical practice. Consequently, currently proposed cTn biomarker cut-offs by the prevailing definitions of PMI might warrant re-assessment, with differentiation in cut-offs for the separate available assays and surgical strategies. To resolve these issues, future prospective studies are warranted to determine the prognostic influence of biomarker release in general and PMI in particular.


Assuntos
Ponte de Artéria Coronária , Infarto do Miocárdio , Humanos , Ponte de Artéria Coronária/efeitos adversos , Infarto do Miocárdio/etiologia , Troponina I , Troponina T , Biomarcadores
5.
Eur Heart J Cardiovasc Pharmacother ; 8(1): 4-12, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32730628

RESUMO

AIMS: Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI. METHODS AND RESULTS: The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37-215) vs. 175 (63-228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32-509) vs. 60 ng/mL (13-206), P = 0.007], immediately after primary PCI [326 ng/mL (94-791) vs. 115 ng/mL (38-326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281-974) vs. 372 ng/mL (95-635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1-5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3-7); P = 0.96]. CONCLUSION: The iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Analgésicos Opioides/efeitos adversos , Humanos , Inibidores da Agregação Plaquetária , Antagonistas do Receptor Purinérgico P2Y , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/uso terapêutico
7.
Am J Cardiol ; 163: 25-31, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34763830

RESUMO

Various definitions of myocardial infarction type 5 after coronary artery bypass grafting (CABG) have been proposed (myocardial infarction [MI-5], also known as peri-procedural MI), using different biomarkers and different and arbitrary cut-off values. This meta-analysis aims to determine the expected release of high-sensitivity cardiac troponin T (hs-cTnT) after CABG in general and after uncomplicated surgery and off-pump CABG in particular. A systematic search was applied to 3 databases. Studies on CABG as a single intervention and reporting on postoperative hs-cTnT concentrations on at least 2 different time points were included. All data on hs-cTnT concentrations were extracted, and mean concentrations at various points in time were stratified. Eventually, 15 studies were included, encompassing 2,646 patients. Preoperative hs-cTnT was 17 ng/L (95% confidence interval [CI] 13 to 20 ng/L). Hs-cTnT peaked at 6 to 8 hours postoperatively (628 ng/L, 95% CI 400 to 856 ng/L; 45x upper reference limit [URL]) and was still increased after 48 hours. In addition, peak hs-cTnT concentration was 614 ng/L (95% CI 282 to 947 ng/L) in patients with a definite uncomplicated postoperative course (i.e., without MI). For patients after off-pump CABG compared to on-pump CABG, the mean peak hs-cTnT concentration was 186 ng/L (95% CI 172 to 200 ng/L, 13 × URL) versus 629 ng/L (95% CI 529 to 726 ng/L, 45 × URL), respectively. In conclusion, postoperative hs-cTnT concentrations surpass most of the currently defined cut-off values for MI-5, even in perceived uncomplicated surgery, suggesting thorough reassessment. Hs-cTnT release differences following on-pump CABG versus off-pump CABG were observed, implying the need for different cut-off values for different surgical strategies.


Assuntos
Ponte de Artéria Coronária , Infarto do Miocárdio/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Troponina T/sangue , Ponte de Artéria Coronária sem Circulação Extracorpórea , Humanos , Infarto do Miocárdio/sangue , Período Perioperatório , Complicações Pós-Operatórias/sangue
9.
PLoS One ; 16(8): e0255477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343174

RESUMO

OBJECTIVE: We aimed 1) to test the applicability of the previously suggested prognostic value of CPET to elderly cardiac rehabilitation patients and 2) to explore the underlying mechanism of the greater improvement in exercise capacity (peak oxygen consumption, VO2) after CR in surgical compared to non-surgical cardiac patients. METHODS: Elderly patients (≥65 years) commencing CR after coronary artery bypass grafting, surgical valve replacement (surgery-group), percutaneous coronary intervention, percutaneous valve replacement or without revascularisation (non-surgery group) were included in the prospective multi-center EU-CaRE study. CPETs were performed at start of CR, end of CR and 1-year-follow-up. Logistic models and receiver operating characteristics were used to determine prognostic values of CPET parameters for major adverse cardiac events (MACE). Linear models were performed for change in peak VO2 (start to follow-up) and parameters accounting for the difference between surgery and non-surgery patients were sought. RESULTS: 1421 out of 1633 EU-CaRE patients performed a valid CPET at start of CR (age 73±5.4, 81% male). No CPET parameter further improved the receiver operation characteristics significantly beyond the model with only clinical parameters. The higher improvement in peak VO2 (25% vs. 7%) in the surgical group disappeared when adjusted for changes in peak tidal volume and haemoglobin. CONCLUSION: CPET did not improve the prediction of MACE in elderly CR patients. The higher improvement of exercise capacity in surgery patients was mainly driven by restoration of haemoglobin levels and improvement in respiratory function after sternotomy. TRIAL REGISTRATION: Netherlands Trial Register, Trial NL5166.


Assuntos
Reabilitação Cardíaca/métodos , Doenças Cardiovasculares/terapia , Teste de Esforço/métodos , Idoso , Ponte de Artéria Coronária , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Modelos Logísticos , Masculino , Consumo de Oxigênio , Intervenção Coronária Percutânea , Prognóstico , Estudos Prospectivos , Curva ROC
10.
Eur J Cardiothorac Surg ; 61(1): 225-232, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34021310

RESUMO

OBJECTIVES: Unanticipated cancellation of a surgical procedure is a common problem, causing distress to the patient and increases in healthcare costs. However, limited evidence exists on the effects of last-minute cancellations of cardiothoracic surgical procedures in particular. The goal of this study was to gain insight into the prevalence of and the reasons for last-minute cancellations and to examine whether cancellation is associated with adverse medical outcomes. METHODS: Patients who were scheduled for elective cardiothoracic surgical procedures between January 2017 and June 2019 were evaluated. The reasons for the cancellations were assigned to the categories medically related or process related. We examined the differences in patient characteristics between those designated as no cancellation, medically related cancellations and process-related cancellations. Lastly, we examined the outcomes of patients who experienced a last-minute cancellation of a scheduled operation. RESULTS: A total of 2111 patients were included; of these, 301 (14.3%) had last-minute cancellations. In 78 (26%) cases, the cancellations were attributable to medical reasons (e.g. infection, comorbidities); 215 (71%) of the cancellations were process related (e.g. another patient in more urgent need of surgery, lack of staff). Almost 99% of the operations with a process-related cancellation were rescheduled compared to only 71.8% of the medically related cancelled operations (P < 0.001). Patients with a medically related cancellation had significantly higher 1-year mortality than patients who had no cancellation (unadjusted hazard ratio 2.50; 95% confidence interval, 1.30-4.78; P = 0.006); after adjustment for the EuroSCORE II, this effect remained significant. CONCLUSIONS: Last-minute cancellations were commonly seen in our cohort, and the reasons for cancellation were significantly related to adverse medical outcomes.


Assuntos
Agendamento de Consultas , Procedimentos Cirúrgicos Eletivos , Adulto , Humanos , Estudos Retrospectivos , Centros de Atenção Terciária
11.
Eur J Prev Cardiol ; 28(5): 513-519, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33989388

RESUMO

AIMS: Socioeconomic status is a strong predictor of cardiovascular health. The aim of this study was to describe the immediate and long-term effects of cardiac rehabilitation (CR) across socioeconomic strata in elderly cardiac patients in Europe. METHODS AND RESULTS: The observational EU-CaRE study is a prospective study with eight CR sites in seven European countries. Patients ≥65 years with coronary heart disease or heart valve surgery participating in CR were consecutively included. Data were obtained at baseline, end of CR and at one-year follow up. Educational level as a marker for socioeconomic status was divided into basic, intermediate and high. The primary endpoint was exercise capacity (peak oxygen consumption (VO2peak)). Secondary endpoints were cardiovascular risk factors, medical treatment and scores for depression, anxiety and quality of life (QoL). A total of 1626 patients were included; 28% had basic, 48% intermediate and 24% high education. A total of 1515 and 1448 patients were available for follow-up analyses at end of CR and one-year, respectively. Patients with basic education were older and more often female. At baseline we found a socioeconomic gradient in VO2peak, lifestyle-related cardiovascular risk factors, anxiety, depression and QoL. The socioeconomic gap in VO2peak increased following CR (p for interaction <0.001). The socioeconomic gap in secondary outcomes was unaffected by CR. The use of evidence-based medication was good in all socioeconomic groups. CONCLUSIONS: We found a strong socioeconomic gradient in VO2peak and cardiovascular risk factors that was unaffected or worsened after CR. To address inequity in cardiovascular health, the individual adaption of CR according to socioeconomic needs should be considered.


Assuntos
Reabilitação Cardíaca , Qualidade de Vida , Idoso , Tolerância ao Exercício , Feminino , Humanos , Consumo de Oxigênio , Estudos Prospectivos , Fatores de Risco
12.
Eur Heart J Digit Health ; 2(3): 477-486, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36713609

RESUMO

Aims: Previous research has shown the possibility to use the pre-operative period to improve a patient's tolerance for surgery. However, there is limited experience with prehabilitation in cardiac surgery. The aim of this study is to evaluate the effect of a comprehensive personalized teleprehabilitation programme on major adverse cardiac events (MACE) in patients scheduled for elective cardiac surgery. Secondary outcomes are post-operative complications, cardiovascular risk factors, quality of life, and cost-effectiveness. Methods and results: In this single-centre randomized controlled trial, patients are eligible for inclusion when they are ≥18 years of age and cardiac surgery is scheduled at least 8 weeks from informed consent. Participants will be randomized to the teleprehabilitation group or the control group. After a digital baseline screening for perioperative risk factors, patients in the intervention arm can pre-operatively be referred to one or more of the prehabilitation modules (functional exercise training, inspiratory muscle training, psychological support, nutritional support, and/or smoking cessation). The programme is targeted at a duration of at least 6 weeks. It is executed by a multidisciplinary team using (video)calls and supported by a custom-made digital platform. During the pre-operative period, the platform is also used to inform patients about their upcoming surgery and for telemonitoring. Conclusion: Reducing perioperative risk factors might result in a reduction of MACE, post-operative complications, length of stay, and cardiovascular risk factors, as well as improved quality of life. Cost-effectiveness will be evaluated.

13.
Int J Cardiol ; 328: 40-45, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33242504

RESUMO

Antiplatelet therapy is one of the cornerstones in the acute treatment of patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI). However, hemodynamic changes and delayed intestinal absorption of P2Y12 inhibitors leads to a delay in the onset of antiplatelet effects resulting in a gap of platelet inhibition. Several strategies have been proposed to bridge this gap, such as pre-hospital administration of antiplatelet therapy, higher loading doses of P2Y12 inhibitors, crushing or chewing tablets, subcutaneous or intravenous administration of platelet inhibitors, or use of pain relievers alternative to opioids that do not delay intestinal absorption of oral platelet inhibitors. These strategies may improve platelet inhibition with the goal of optimizing clinical outcomes in the acute phase of STEMI. In this review we present current and future insights for bridging the gap in platelet inhibition in STEMI patients undergoing primary PCI.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Plaquetas , Humanos , Inibidores da Agregação Plaquetária , Antagonistas do Receptor Purinérgico P2Y , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Resultado do Tratamento
14.
Eur Heart J ; 41(33): 3132-3140, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31994703

RESUMO

AIMS: To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). METHODS AND RESULTS: In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked ∼30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%). CONCLUSIONS: Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for ≥8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.


Assuntos
Inibidores da Agregação Plaquetária , Antagonistas do Receptor Purinérgico P2Y , Plaquetas , Humanos , Organofosfonatos , Agregação Plaquetária , Testes de Função Plaquetária , Pirimidinas , Síndrome
15.
BMC Fam Pract ; 20(1): 149, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675925

RESUMO

BACKGROUND: Cardiovascular diseases (CVD) contribute considerably to mortality and morbidity. Prevention of CVD by lifestyle change and medication is important and needs full attention. In the Netherlands an integrated programme for cardiovascular risk management (CVRM), based on the Chronic Care Model (CCM), has been introduced in primary care in many regions in recent years, but its effects are unknown. In the ZWOT-CASE study we will assess the effect of integrated care for CVRM in the region of Zwolle on two major cardiovascular risk factors: systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-cholesterol) in patients with or at high risk of CVD. METHODS: This study is a pragmatic observational study comparing integrated care for CVRM with usual care among patients aged 40-80 years with CVD (n = 370) or with a high CVD risk (n = 370) within 26 general practices. After 1 yr follow-up, primary outcomes (SBP and LDL-cholesterol level) are measured. Secondary outcomes include lifestyle habits (smoking, dietary habits, alcohol use, physical activity), risk factor awareness, 10-year risk of cardiovascular morbidity or mortality, health care consumption, patient satisfaction and quality of life. CONCLUSION: The ZWOT-CASE study will provide insight in the effects of integrated care for CVRM in general practice in patients with CVD or at high CVD risk. TRIAL REGISTRATION: The ZWOlle Transmural Integrated Care for CArdiovaScular Risk Management Study; ClinicalTrials.gov ; Identifier: NCT03428061; date of registration: 09-02-2018; This study has been retrospectively registered.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Medicina Geral/métodos , Gestão de Riscos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Prestação Integrada de Cuidados de Saúde/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Avaliação de Programas e Projetos de Saúde , Comportamento de Redução do Risco
16.
N Engl J Med ; 381(17): 1621-1631, 2019 10 24.
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.).


Assuntos
Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Citocromo P-450 CYP2C19/genética , Genótipo , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Medicina de Precisão , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Método Simples-Cego , Stents , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico
17.
Eur Heart J Cardiovasc Pharmacother ; 5(3): 127-138, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30084902

RESUMO

AIMS: Proton-pump inhibitors (PPIs) are commonly prescribed in acute coronary syndrome (ACS) patients on antiplatelet therapy. We studied PPI prescription in ACS patients in the era of novel P2Y12 inhibitors and assessed the association between PPI use and clinical outcomes. METHODS AND RESULTS: Between 2010 and 2014, we included all consecutive ACS patients admitted to a Dutch tertiary hospital. The main outcome was PPI prescription at discharge. Additionally, we present 1-year mortality and 30-day cardiovascular and bleeding outcomes. Of 4595 ACS patients with known discharge medication, 63.9% received a PPI. PPI-treated patients were older (67.1 ± 12.5 vs. 63.0 ± 13.3, P < 0.001). PPI treatment at discharge increased from 34.7% in 2010 to 88.7% in 2014 (P < 0.001). Concurrently, ticagrelor prescription at discharge increased from 0.0% to 48.6% in 2014 (P < 0.001), while clopidogrel prescription decreased from 78.6% in 2010 to 28.7% in 2014 (P < 0.001). PPI treatment was associated with reductions in death or myocardial infarction (MI) [adjusted hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.76] and death, MI or stroke (adjusted HR 0.33, 95% CI 0.14-0.81) at 30-days post-discharge. However, this association was not present in subgroup analyses of patients treated with clopidogrel or ticagrelor. CONCLUSION: In this single-centre registry, PPI prescription in ACS patients doubled between 2010 and 2014. PPI treatment at discharge was associated with a reduction in death, MI, or stroke at 30-days post-discharge, mainly driven by a reduction in MI. There were no differences gastrointestinal bleeding between patients treated with or without a PPI. PPI treatment may serve as a marker of improved therapies and outcome, rather than causing a reduction in cardiovascular events.


Assuntos
Síndrome Coronariana Aguda/terapia , Hemorragia Gastrointestinal/prevenção & controle , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea/tendências , Inibidores da Agregação Plaquetária/efeitos adversos , Padrões de Prática Médica/tendências , Inibidores da Bomba de Prótons/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Acidente Vascular Cerebral/prevenção & controle , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Prescrições de Medicamentos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Recidiva , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
18.
Am J Cardiol ; 121(10): 1123-1128, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29606324

RESUMO

Previous studies found that patients with an acute coronary syndrome (ACS) due to occlusion of the left circumflex (LC) coronary artery often present without ST-elevation, leading to a delay in diagnosis and revascularization, a larger infarct size, and a worse prognosis. In this subgroup analysis of the ELISA-3 study (early or late intervention in high-risk non-ST-segment elevation acute coronary syndromes [NSTE-ACS]) incidence, characteristics and prognosis of LC-related NSTE-ACS was investigated, and the outcome of early versus late invasive strategy was compared. In 383 of 542 patients the culprit vessel could be identified, with the LC artery in 112 (29%) of them. Patients with LC-related ACS had more often single vessel disease and underwent percutaneous coronary intervention more and CABG less frequently. The primary end point of the combined incidences of death, myocardial infarction, and recurrent ischemia at 30-day follow-up occurred in 9.0% of LC versus 16.5% of non-LC-related ACS (p = 0.057). Enzymatic infarct size and incidence of bleeding were comparable. Of patients with LC-related ACS, 62 were assigned to an early and 50 to a late invasive treatment with a median time from admission to angiography of 5.5 and 65.7 hours, respectively. The primary end point occurred in 9.7% and 8.0%, respectively (p = 1.00) with comparable enzymatic infarct size and bleeding. In conclusion, no significant differences in outcome were found between patients with an LC- and a non-LC-related NSTE-ACS. In LC-related NSTE-ACS, angiography within 12 hours of admission is feasible but not superior to angiography after more than 48 hours.


Assuntos
Síndrome Coronariana Aguda/terapia , Tratamento Conservador , Ponte de Artéria Coronária , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/epidemiologia , Idoso , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Feminino , Hemorragia/epidemiologia , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Prognóstico , Recidiva , Fatores de Tempo
19.
Int J Vasc Med ; 2017: 1857069, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29085679

RESUMO

The aim of this study was to investigate the impact of perioperative screening with modified transesophageal echocardiography (A-View method). We compared, in consecutive patients who underwent cardiac surgery between 2006 and 2014, 30-day mortality and in-hospital stroke incidence, operated either with perioperative modified TEE screening (intervention group) or only with conventional TEE screening (control group). Of the 8,605 study patients, modified TEE was applied in 1,391 patients (16.2%). Patients in the intervention group were on average older (71 versus 68 years, p < 0.001) and more often females (31.0% versus 28.0%, p < 0.001) and had a higher predicted mortality (EuroSCORE I: 5.9% versus 4.0%, p < 0.001). The observed 30-day mortality was 2.2% and 2.5% in both groups, respectively, with multivariable and propensity-score adjusted relative risks (RRs) of 0.70 (95% CI: 0.50-1.00, p = 0.05) and 0.67 (95% CI: 0.45-0.98, p = 0.04). In-hospital stroke was 2.9% and 2.1% in both groups, respectively, with adjusted RRs of 1.03 (95% CI: 0.73-1.45) and 1.01 (95% CI: 0.71-1.43). In patients undergoing cardiac surgery, use of perioperative screening for aortic atherosclerosis with modified TEE was associated with lower postoperative mortality, but not stroke, as compared to patients operated on without such screening.

20.
Int J Vasc Med ; 2017: 1874395, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28852575

RESUMO

In patients undergoing cardiac surgery, use of perioperative screening for aortic atherosclerosis with modified TEE (A-View method) was associated with lower postoperative mortality, but not stroke, as compared to patients operated on without such screening. At the time of clinical implementation and validation, we did not yet standardize the indications for modified TEE and the changes in patient management in the presence of aortic atherosclerosis. Therefore, we designed a protocol, which combined the diagnosis of atherosclerosis of thoracic aorta and the subsequent considerations with respect to the intraoperative management and provides a systematic approach to reduce the risk of cerebral complications.

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