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1.
Circulation ; 150(4): 317-335, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39038086

RESUMO

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.


Assuntos
Síndrome Coronariana Aguda , Terapia Antiplaquetária Dupla , Inibidores da Agregação Plaquetária , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea , Fatores de Tempo , Resultado do Tratamento , Cloridrato de Prasugrel/uso terapêutico , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/efeitos adversos , Esquema de Medicação
3.
Vasc Med ; 29(3): 286-295, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38898631

RESUMO

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified. METHODS: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine. RESULTS: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, p = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, p = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [p = 0.0004] and 35.3% vs 26.7% [p = 0.0099], respectively). CONCLUSIONS: Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities.


Assuntos
Anomalias dos Vasos Coronários , Transtornos de Enxaqueca , Sistema de Registros , Doenças Vasculares , Humanos , Feminino , Masculino , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/diagnóstico , Pessoa de Meia-Idade , Doenças Vasculares/epidemiologia , Doenças Vasculares/congênito , Doenças Vasculares/diagnóstico , Anomalias dos Vasos Coronários/epidemiologia , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico , Adulto , Estudos Prospectivos , Fatores de Risco , Avaliação da Deficiência , Idoso , Displasia Fibromuscular/epidemiologia , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico , Displasia Fibromuscular/diagnóstico por imagem , Depressão/epidemiologia , Depressão/diagnóstico
4.
Eur J Cardiothorac Surg ; 65(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830050

RESUMO

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.


Assuntos
Índice de Massa Corporal , Ponte de Artéria Coronária , Obesidade , Sobrepeso , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ponte de Artéria Coronária/efeitos adversos , Obesidade/complicações , Sobrepeso/complicações , Sobrepeso/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
6.
Nat Med ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796655

RESUMO

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l-1 at baseline were randomized to receive clazakizumab (2.5 mg, 5 mg or 10 mg, n = 32 per dose group) or placebo (n = 31) every 4 weeks. The primary endpoint was the change from baseline in hs-CRP to week 12, expressed as the geometric mean ratio. Clazakizumab treatment signficantly reduced serum hs-CRP concentrations at week 12 by 86%, 90% and 92% relative to placebo in patients randomized to 2.5 mg, 5 mg or 10 mg clazakizumab, respectively (all P < 0.0001), meeting the primary outcome. With regard to secondary endpoints, clazakizumab treatment reduced serum fibrinogen, amyloid A, secretory phospholipase A2, and lipoprotein(a) concentrations, as well as increased mean serum albumin concentrations at 12 weeks, relative to placebo. The proportion of patients who achieved hs-CRP < 2.0 mg l-1 was 79%, 82% and 79% in the 2.5 mg, 5 mg and 10 mg clazakizumab groups, respectively, compared with 0% of placebo-treated patients. With regard to safety, no cases of sustained grade 3 or 4 thrombocytopenia or neutropenia were observed. Serious infections were seen with similar frequency in the placebo, clazakizumab 2.5 mg and clazakizumab 5 mg groups, but were numerically more frequent in the clazakizumab 10 mg group. The results of this trial indicate that in patients receiving maintenance dialysis, clazakizumab reduced inflammatory biomarkers associated with cardiovascular events. ClinicalTrials.gov registration: NCT05485961 .

7.
Health Sci Rep ; 7(4): e2031, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650733

RESUMO

Background and Aims: Mechanical thrombectomy (MT) treatments for pulmonary embolism (PE) have yet to be compared directly. We aimed to determine if patient outcomes varied following treatment of PE with different MT devices. Methods: All PE encounters with an index treatment of MT between January 2018 and March 2022 were analyzed for in-hospital mortality, discharge to home, and 30-day readmission outcomes in the PINC AI™ Healthcare Database. MT devices used in each encounter were extracted from hospital charge description free-text fields using keyword text and fuzzy matching. Unadjusted and adjusted logistic regression was used to model outcomes by device. Results: A total of 5893 encounters were identified using MT as the sole index PE treatment and 1812 using MT with another treatment. Of these, 41% had insufficient information to identify the devices used (unspecified MT), 33% used the FlowTriever System (large-bore volume-controlled aspiration MT), 23% the Indigo System (continuous aspiration MT), and 3% some other MT. Large-bore volume-controlled aspiration MT was used with other treatments 13% of the time compared with 23% and 39% for unspecified MT and continuous aspiration MT, respectively. Adjusted logistic regression modeling revealed the odds of in-hospital mortality were significantly higher for patients treated with unspecified MT ([OR] = 1.42, 95% confidence interval [CI]: [1.10-1.83], p = 0.008) or continuous aspiration MT (OR = 1.63, 95% CI: [1.21-2.19], p = 0.001) compared with large-bore volume-controlled aspiration MT. Discharge to home was significantly lower in these same groups (OR = 0.84, 95% CI: [0.73-0.96], p = 0.01, and OR = 0.63, 95% CI: [0.53-0.74], p < 0.001, respectively), but readmission risks at 30 days were comparable (OR = 1.08, 95% CI: [0.84-1.38], p = 0.56, and OR = 1.20, 95% CI: [0.89-1.62], p = 0.24, respectively). Conclusion: PE outcomes and treatment patterns differ significantly based on the type of MT utilized. Clinical studies directly comparing MT treatments are needed to further understand optimal treatment of PE.

8.
J Am Coll Cardiol ; 83(22): 2163-2174, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38588930

RESUMO

BACKGROUND: The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI. OBJECTIVES: This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI. METHODS: The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo. RESULTS: The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis). CONCLUSIONS: Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis-related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations.


Assuntos
Apolipoproteína A-I , Infarto do Miocárdio , Humanos , Masculino , Feminino , Método Duplo-Cego , Infarto do Miocárdio/epidemiologia , Pessoa de Meia-Idade , Idoso , Recidiva , Infusões Intravenosas , Lipoproteínas HDL
9.
Am J Cardiol ; 222: 167-174, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38641190

RESUMO

The number of different methods of reperfusion therapy to treat venous thromboembolism (VTE) has increased substantially. Nevertheless, investigation of data representativeness and device-level use in administrative databases has been limited. Using the National Inpatient Sample (NIS) and the PINC AI Healthcare Database (PHD), all hospital encounters with a diagnosis code of VTE were identified between January 1, 2016 and December 31, 2020. Patient demographics and trends in treatment modalities were evaluated over time. An algorithm was developed to identify specific devices used for VTE treatment in the PHD cohort. A total of 145,870 patients with VTE treated with reperfusion therapy were identified in the NIS (pulmonary embolism [PE] 88,725, isolated deep vein thrombosis [iDVT] 57,145) and 39,311 in the PHD (PE 25,383, iDVT 13,928). Patient demographics were qualitatively similar in the NIS and PHD. Over time, there was a significant increase in the use of mechanical thrombectomy in the PE and iDVT populations (p <0.05 in both databases), with catheter-directed thrombolysis use plateauing in PE (p = 0.83 and p = 0.14 in NIS and PHD, respectively) and significantly decreasing for the iDVT population (p <0.05 in both databases). In the PHD cohort, specific reperfusion devices were identified in 14,105 patients (PE 9,098, iDVT 5,007). In conclusion, the use of mechanical thrombectomy for the treatment of VTE has increased over time, whereas the rates of catheter-directed thrombolysis therapy have remained stagnant or decreased. Further research is needed to understand the uptake of these treatment modalities and the unique abilities of the PHD to study specific device therapy in the VTE population.


Assuntos
Bases de Dados Factuais , Tromboembolia Venosa , Humanos , Masculino , Feminino , Tromboembolia Venosa/epidemiologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Idoso , Terapia Trombolítica/métodos , Embolia Pulmonar/terapia , Pacientes Internados , Trombectomia , Trombose Venosa/epidemiologia , Trombose Venosa/terapia , Estudos Retrospectivos
10.
N Engl J Med ; 390(17): 1560-1571, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38587254

RESUMO

BACKGROUND: Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear. METHODS: We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up. RESULTS: A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P = 0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group. CONCLUSIONS: Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.).


Assuntos
Apolipoproteína A-I , Lipoproteínas HDL , Infarto do Miocárdio , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apolipoproteína A-I/administração & dosagem , Apolipoproteína A-I/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/complicações , Método Duplo-Cego , Infusões Intravenosas , Estimativa de Kaplan-Meier , Lipoproteínas HDL/sangue , Lipoproteínas HDL/metabolismo , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/mortalidade , Recidiva , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle , Fatores de Risco
12.
J Am Heart Assoc ; 13(7): e032819, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38533943

RESUMO

BACKGROUND: Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry-based cohort, we documented prevalence of lifetime and past-month SCAD-induced PTSD, as well as related treatment seeking, and examined a range of health-relevant correlates of SCAD-induced PTSD. METHODS AND RESULTS: Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD-induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD-induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD-induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past-month PTSD. Of 811 patients ever reporting any SCAD-induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD-induced PTSD diagnoses reported never receiving trauma-related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past-month PTSD symptom severity in multivariable regression models. Greater past-month SCAD-induced PTSD symptoms were associated with greater past-week sleep disturbance and worse past-month disease-specific health status when adjusting for various risk factors. CONCLUSIONS: Given the high prevalence of SCAD-induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.


Assuntos
Anomalias dos Vasos Coronários , Transtornos de Estresse Pós-Traumáticos , Doenças Vasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Coronária , Vasos Coronários , Sistema de Registros , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/congênito
13.
Am Heart J ; 272: 11-22, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38458371

RESUMO

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.


Assuntos
Aspirina , Intervenção Coronária Percutânea , Doença Arterial Periférica , Inibidores da Agregação Plaquetária , Ticagrelor , Humanos , Ticagrelor/uso terapêutico , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Doença Arterial Periférica/complicações , Intervenção Coronária Percutânea/métodos , Masculino , Feminino , Idoso , Inibidores da Agregação Plaquetária/uso terapêutico , Pessoa de Meia-Idade , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Terapia Antiplaquetária Dupla/métodos , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/epidemiologia
14.
Thromb Res ; 235: 116-121, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335566

RESUMO

The mechanism underlying thrombus formation in acute coronary syndrome (ACS) involves both platelets and thrombin. While both pathways are targeted in acute care, platelet inhibition has been predominantly administered in the chronic phase, yet thrombin plays a key role in platelet activation and fibrin formation. Among ACS patients, there is also a persistent chronic increase in thrombin generation, which is associated with a higher rate of adverse events. In the setting of post-ACS care with rivaroxaban or vorapaxar, targeting thrombin has been associated with decreased thrombin generation and reduced cardiovascular events, but has been associated with increased bleeding risk. We explored the evidence supporting thrombin generation in the pathophysiology of recurrent events post-ACS and the role of thrombin as a viable therapeutic target. One specific target is factor XI inhibition, which is involved in thrombin generation, but may also allow for the preservation of normal hemostasis.


Assuntos
Síndrome Coronariana Aguda , Humanos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/complicações , Trombina/fisiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Hemorragia/tratamento farmacológico
16.
J Am Coll Cardiol ; 83(1): 35-43, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38171708

RESUMO

BACKGROUND: Contemporary care patterns/outcomes in high-risk pulmonary embolism (PE) patients are unknown. OBJECTIVES: This study sought to characterize the management of high-risk PE patients and identify factors associated with poor outcomes. METHODS: A retrospective analysis of the PERT (Pulmonary Embolism Response Team) Consortium Registry was performed. Patients presenting with intermediate-risk PE, high-risk PE, and catastrophic PE (those with hemodynamic collapse) were identified. Patient characteristics were compared with chi-square testing for categorical covariates and Student's t-test for continuous covariates. Multivariable logistic regression was used to assess associations between clinical characteristics and outcomes in the high-risk population. RESULTS: Of 5,790 registry patients, 2,976 presented with intermediate-risk PE and 1,442 with high-risk PE. High-risk PE patients were more frequently treated with advanced therapies than intermediate-risk PE patients (41.9% vs 30.2%; P < 0.001). In-hospital mortality (20.6% vs 3.7%; P < 0.001) and major bleeding (10.5% vs. 3.5%; P < 0.001) were more common in high-risk PE. Multivariable regression analysis demonstrated vasopressor use (OR: 4.56; 95% CI: 3.27-6.38; P < 0.01), extracorporeal membrane oxygenation use (OR: 2.86; 95% CI: 1.12-7.30; P = 0.03), identified clot-in-transit (OR: 2.26; 95% CI: 1.13-4.52; P = 0.02), and malignancy (OR: = 1.70; 95% CI: 1.13-2.56; P = 0.01) as factors associated with in-hospital mortality. Catastrophic PE patients (n = 197 [13.7% of high-risk PE patients]) had higher in-hospital mortality (42.1% vs 17.2%; P < 0.001) than those presenting with noncatastrophic high-risk PE. Extracorporeal membrane oxygenation (13.3% vs. 4.8% P < 0.001) and systemic thrombolysis (25% vs 11.3%; P < 0.001) were used more commonly in catastrophic PE. CONCLUSIONS: In the largest analysis of high-risk PE patients to date, mortality rates were high with the worst outcomes among patients with hemodynamic collapse.


Assuntos
Hemorragia , Embolia Pulmonar , Humanos , Estudos Retrospectivos , Fatores de Risco , Hemorragia/etiologia , Modelos Logísticos , Embolia Pulmonar/terapia , Terapia Trombolítica/efeitos adversos , Resultado do Tratamento
17.
Int J Technol Assess Health Care ; 40(1): e13, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38282208

RESUMO

OBJECTIVES: Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice. METHODS: An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized. RESULTS: Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals. CONCLUSIONS: Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.


Assuntos
Projetos de Pesquisa , Tecnologia , Humanos , Avaliação da Tecnologia Biomédica
18.
Cochrane Database Syst Rev ; 1: CD014678, 2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38264795

RESUMO

BACKGROUND: Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited. OBJECTIVES: To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science, and two clinical trial registers in September 2022 with no language restrictions. We checked the reference lists of included studies for any additional trials. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects pairwise analyses using Review Manager Web, and network meta-analysis using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons and allow ranking of treatments on a continuous 0-to-1 scale. MAIN RESULTS: We identified seven eligible RCTs, including an ongoing trial that we could not include in the analysis. Of the six RCTs involving 33,039 participants, three RCTs compared rivaroxaban with placebo, two RCTs compared apixaban with placebo, and one RCT compared dabigatran with placebo. All participants in the six RCTs received concomitant antiplatelet therapy. The available evidence suggests that rivaroxaban compared with placebo reduces the rate of all-cause mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.69 to 0.98; number needed to treat for an additional beneficial outcome (NNTB) 250; 3 studies, 21,870 participants; high certainty) and probably reduces cardiovascular mortality (RR 0.83, 95% CI 0.69 to 1.01; NNTB 250; 3 studies, 21,870 participants; moderate certainty). There is probably little or no difference between apixaban and placebo in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35; number needed to treat for an additional harmful outcome (NNTH) 334; 2 studies, 8638 participants; moderate certainty) and cardiovascular mortality (RR 0.99, 95% CI 0.77 to 1.27; number needed to treat not applicable; 2 studies, 8638 participants; moderate certainty). Dabigatran may reduce the rate of all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06; NNTB 63; 1 study, 1861 participants; low certainty). Dabigatran compared with placebo may have little or no effect on cardiovascular mortality, although the point estimate suggests benefit (RR 0.72, 95% CI 0.34 to 1.52; NNTB 143; 1 study, 1861 participants; low certainty). Two of the investigated NOACs were associated with an increased risk of major bleeding compared to placebo: apixaban (RR 2.41, 95% CI 1.44 to 4.06; NNTH 143; 2 studies, 8544 participants; high certainty) and rivaroxaban (RR 3.31, 95% CI 1.12 to 9.77; NNTH 125; 3 studies, 21,870 participants; high certainty). There may be little or no difference between dabigatran and placebo in the risk of major bleeding (RR 1.74, 95% CI 0.22 to 14.12; NNTH 500; 1 study, 1861 participants; low certainty). The results of the network meta-analysis were inconclusive between the different NOACs at all individual doses for all primary outcomes. However, low-certainty evidence suggests that apixaban (combined dose) may be less effective than rivaroxaban and dabigatran for preventing all-cause mortality after AMI in people without an indication for anticoagulation. AUTHORS' CONCLUSIONS: Compared with placebo, rivaroxaban reduces all-cause mortality and probably reduces cardiovascular mortality after AMI in people without an indication for anticoagulation. Dabigatran may reduce the rate of all-cause mortality and may have little or no effect on cardiovascular mortality. There is probably no meaningful difference in the rate of all-cause mortality and cardiovascular mortality between apixaban and placebo. Moreover, we found no meaningful benefit in efficacy outcomes for specific therapy doses of any investigated NOACs following AMI in people without an indication for anticoagulation. Evidence from the included studies suggests that rivaroxaban and apixaban increase the risk of major bleeding compared with placebo. There may be little or no difference between dabigatran and placebo in the risk of major bleeding. Network meta-analysis did not show any superiority of one NOAC over another for our prespecified primary outcomes. Although the evidence suggests that NOACs reduce mortality, the effect size or impact is small; moreover, NOACs may increase major bleeding. Head-to-head trials, comparing NOACs against each other, are required to provide more solid evidence.


Assuntos
Dabigatrana , Infarto do Miocárdio , Humanos , Rivaroxabana , Metanálise em Rede , Inibidores da Agregação Plaquetária , Anticoagulantes , Hemorragia
19.
JAMA Cardiol ; 9(2): 101-102, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37950739
20.
Am J Cardiol ; 208: 16-24, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37806185

RESUMO

Repeat coronary revascularization is a common adverse event after successful percutaneous coronary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomly allocated to aspirin or placebo for 1 year. The primary end point of this analysis was CDR within 12 months after randomization. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clinically relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confidence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p = 0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p = 0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p = 0.004) than ticagrelor plus aspirin. In conclusion, among high-risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242).


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Ticagrelor/uso terapêutico , Inibidores da Agregação Plaquetária , Intervenção Coronária Percutânea/métodos , Quimioterapia Combinada , Aspirina , Infarto do Miocárdio/terapia , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
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