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2.
Clin Cardiol ; 42(10): 1028-1040, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31317575

RESUMO

Clinical guidelines for the treatment of patients with non-ST-segment elevation myocardial infarction (NSTEMI) recommend an invasive strategy with cardiac catheterization, revascularization when clinically appropriate, and initiation of dual antiplatelet therapy regardless of whether the patient receives revascularization. However, although patients with NSTEMI have a higher long-term mortality risk than patients with ST-segment elevation myocardial infarction (STEMI), they are often treated less aggressively; with those who have the highest ischemic risk often receiving the least aggressive treatment (the "treatment-risk paradox"). Here, using evidence gathered from across the world, we examine some reasons behind the suboptimal treatment of patients with NSTEMI, and recommend approaches to address this issue in order to improve the standard of healthcare for this group of patients. The challenges for the treatment of patients with NSTEMI can be categorized into four "P" factors that contribute to poor clinical outcomes: patient characteristics being heterogeneous; physicians underestimating the high ischemic risk compared with bleeding risk; procedure availability; and policy within the healthcare system. To address these challenges, potential approaches include: developing guidelines and protocols that incorporate rigorous definitions of NSTEMI; risk assessment and integrated quality assessment measures; providing education to physicians on the management of long-term cardiovascular risk in patients with NSTEMI; and making stents and antiplatelet therapies more accessible to patients.

3.
N Engl J Med ; 380(16): 1509-1524, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883055

RESUMO

BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).


Assuntos
Síndrome Coronariana Aguda/complicações , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Pirazóis/efeitos adversos , Piridonas/efeitos adversos
4.
J Am Coll Cardiol ; 73(22): 2819-2828, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-30898608

RESUMO

BACKGROUND: The efficacy of ticagrelor in the long-term post-ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. OBJECTIVES: The purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. METHODS: This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months. RESULTS: The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups. CONCLUSION: Among patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088).

5.
Clin Cardiol ; 41(10): 1322-1327, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30098028

RESUMO

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with ST-segment elevation myocardial infarction (STEMI). In patients with STEMI who cannot undergo timely primary PCI, pharmacoinvasive treatment is recommended, comprising immediate fibrinolytic therapy with subsequent coronary angiography and rescue PCI if needed. Improving clinical outcomes following fibrinolysis remains of great importance for the many patients globally for whom rapid treatment with primary PCI is not possible. For patients with acute coronary syndrome who underwent primary PCI, the PLATO trial demonstrated superior efficacy of ticagrelor relative to clopidogrel. Results in the predefined subgroup of patients with STEMI were consistent with the overall PLATO trial. Patients who received fibrinolytic therapy in the 24 hours before randomization were excluded from PLATO, and there is thus a lack of data on the safety of using ticagrelor in conjunction with fibrinolytic therapy in the first 24 hours after STEMI. The TREAT study addresses this knowledge gap; patients with STEMI who had symptom onset within the previous 24 hours and had received fibrinolytic therapy (of whom 89.4% had also received clopidogrel) were randomized to treatment with ticagrelor or clopidogrel (median time between fibrinolysis and randomization: 11.5 hours). At 30 days, ticagrelor was found to be non-inferior to clopidogrel for the primary safety outcome of Thrombolysis in Myocardial Infarction (TIMI)-defined first major bleeding. Considering together the results of the PLATO and TREAT studies, initiating or switching to treatment with ticagrelor within the first 24 hours after STEMI in patients receiving fibrinolysis is reasonable.


Assuntos
Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Terapia Trombolítica/métodos , Ticagrelor/uso terapêutico , Saúde Global , Humanos , Incidência , Inibidores da Agregação de Plaquetas/uso terapêutico , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Taxa de Sobrevida/tendências
6.
Am Heart J ; 202: 89-96, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29908420

RESUMO

BACKGROUND: The safety and efficacy of ticagrelor in patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain. OBJECTIVES: The primary objective of the TicagRElor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short-term safety of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of ticagrelor compared with clopidogrel at 12-months. DESIGN: The TREAT trial is a multicenter, randomized, phase III, Prospective randomized open blinded end-point (PROBE) study that enrolled 3,799 patients in 152 sites from 10 countries. Following administration of fibrinolytic therapy patients were randomized to a loading dose of ticagrelor 180 mg or clopidogrel 300 mg followed by a maintenance dose of ticagrelor 90 mg twice daily or clopidogrel 75 mg/day for 12-months. The primary outcome is the rate of TIMI major bleeding at 30-days and will be assessed for non-inferiority using an intention-to-treat analysis. Co-treatments include aspirin and anticoagulants. Other evidence based therapies are also recommended. Secondary efficacy outcome include a composite of death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic event. All-cause mortality as well as individual components of the combined efficacy endpoint will also be ascertained. SUMMARY: TREAT is an international randomized controlled trial comparing ticagrelor with clopidogrel in STEMI patients treated with fibrinolytic therapy. The results of this trial will inform clinical practice and international guidelines.


Assuntos
Clopidogrel/uso terapêutico , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Adulto , Idoso , Anticoagulantes/uso terapêutico , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Projetos de Pesquisa , Infarto do Miocárdio com Supradesnível do Segmento ST , Método Simples-Cego , Ticagrelor/efeitos adversos
7.
JAMA Cardiol ; 3(5): 391-399, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29525822

RESUMO

Importance: The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain. Objective: To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. Design, Setting and Participants: We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. Interventions: Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. Main Outcomes and Measures: The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days. Results: The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95% CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57). Conclusions and Relevance: In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days. Trial Registration: clinicaltrials.gov Identifier: NCT02298088.


Assuntos
Clopidogrel/uso terapêutico , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Ticagrelor/uso terapêutico , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Ticagrelor/efeitos adversos
8.
Kardiologiia ; 57(9): 42-46, 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31713505

RESUMO

AIM: To perform a randomized, open-label comparison of average time in therapeutic range (TTR) of international normalized ratio (INR) using two approaches to initial warfarin dosing during hospitalization: the standard method and the one using individual patient characteristics (clinical algorithm - the studied approach). MATERIALS AND METHODS: We randomly assigned 60 patients with different indications for vitamin K antagonist therapy to the studied approach (n=31, intervention group) or to the standard method (n=29, control group). А target INR range for all patients was 2.0 to 3.0. RESULTS: The average TTR and portions of INR values within target range during the whole time of drug dosing turned out to be small. TTR was 22.4% with standard method and 21.4% with clinical algorithm, which was well below desired 60%. CONCLUSION: The opportunities for achieving target INR in inpatient settings, regardless of warfarin dosing regimen, are limited.


Assuntos
Anticoagulantes/uso terapêutico , Varfarina/uso terapêutico , Algoritmos , Hospitalização , Humanos , Coeficiente Internacional Normatizado
9.
Curr Med Res Opin ; 33(7): 1269-1276, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28420281

RESUMO

OBJECTIVE: This study sought to describe the short- and long-term (up to 2 years) antithrombotic management patterns in a real-life setting for patients hospitalized for an acute coronary syndrome (ACS) event, and to document clinical outcomes. RESEARCH DESIGN AND METHODS: EPICOR-RUS was a multicenter (34 centers), prospective, observational, longitudinal cohort study conducted across Russia on antithrombotic management in hospitalized (within 24 hours of symptom onset) ACS patients with 2 year follow-up. CLINICAL TRIAL REGISTRATION: NCT01373957. RESULTS: A total of 600 ACS patients (71.1% male, mean age 60 years) were enrolled; 599 were included for analysis. Diagnosis comprised STEMI (n = 375, 62.6%), NSTEMI (n = 147, 24.5%), and unstable angina (UA) (n = 77, 12.9%). Percutaneous coronary intervention (PCI) was conducted in 64.3% of patients with STEMI (with or without thrombolysis), 36.7% with NSTEMI, and 58.4% with UA. There was undertreatment with dual antiplatelet therapy (DAPT) for STEMI, NSTEMI, and UA: 14.7%, 25.9% and 16.9% of patients, respectively, were not receiving DAPT during hospitalization, and 10.1%, 21.8% and 16.9% at discharge. Post-discharge, of the STEMI group, only 72.4% of patients who were managed by PCI and 39.8% of conservatively treated patients received DAPT at 12 months. The respective figures in the NSTEMI group were 77.3% and 26.4%. In the STEMI cohort the cumulative incidence of all-cause mortality was 3.2% at 1 year and 5.1% at 2 years of follow-up; in the NSTEMI cohort this was 2.7% and 4.8%, respectively. There were no deaths by 12 months and one death by 24 months (1.3%) in the UA population. CONCLUSION: Despite evidence-based guidelines for the management of ACS, the real-world setting in Russia shows discrepancies in clinical practice, highlighting the need for improvements for the optimal management of high-risk patients with ACS.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Angina Instável/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Intervenção Coronária Percutânea/métodos , Idoso , Feminino , Seguimentos , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Alta do Paciente , Estudos Prospectivos , Federação Russa
10.
Cardiovasc Ther ; 34(4): 191-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26990595

RESUMO

AIMS: Concomitant renin-angiotensin-aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF. METHODS: This was an open-label, noncontrolled single-sequence study. After a 24-h run-in period, patients (n = 30) with HFrEF (EF ≤ 40%; NYHA class II-IV) received LCZ696 100 mg twice daily (bid) for 7 days and 200 mg bid for 14 days, along with standard treatment for heart failure (HF) (except angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]). RESULTS: On Day 21, significant increases were observed in the plasma biomarkers indicative of neprilysin and RAAS inhibition (ratio-to-baseline: cyclic guanosine monophosphate [cGMP], 1.38; renin concentration and activity, 3.50 and 2.27, respectively; all, P < 0.05). Plasma NT-proBNP levels significantly decreased at all the time points on Days 7 and 21; plasma aldosterone and endothelin-1 levels significantly decreased on Day 21 (all, P < 0.05). Following administration of LCZ696, the Cmax of sacubitril (neprilysin inhibitor prodrug), LBQ657 (active neprilysin inhibitor), and valsartan were reached within 0.5, 2.5, and 2 h. Between 100- and 200-mg doses, the Cmax and AUC0-12 h for sacubitril and LBQ657 were approximately dose-proportional while that of valsartan was less than dose-proportional. CONCLUSIONS: Treatment with LCZ696 for 21 days was well tolerated and resulted in plasma biomarker changes indicative of neprilysin and RAAS inhibition in patients with HF. The pharmacokinetic exposure of the LCZ696 analytes in patients with HF observed in this study is comparable to that observed in the pivotal Phase III study.


Assuntos
Aminobutiratos/farmacocinética , Antagonistas de Receptores de Angiotensina/farmacocinética , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Tetrazóis/farmacocinética , Função Ventricular Esquerda , Idoso , Aldosterona/sangue , Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/sangue , Área Sob a Curva , Biomarcadores/sangue , Doença Crônica , Esquema de Medicação , Endotelina-1/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Neprilisina/antagonistas & inibidores , Neprilisina/metabolismo , Fragmentos de Peptídeos/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Federação Russa , Tetrazóis/administração & dosagem , Resultado do Tratamento
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