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1.
J Stroke Cerebrovasc Dis ; 30(2): 105520, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33310594

RESUMO

BACKGROUND: Ticagrelor is a novel antiplatelet agent that is frequently used for secondary prevention in coronary artery disease and has emerging evidence in stroke after the recent results of SOCRATES and THALES trials. The use of intravenous thrombolysis with alteplase in acute ischemic stroke (AIS) patients on ticagrelor is a topic of debate as the safety profile of ticagrelor in this setting is not well established. METHODS: We identified consecutive AIS patients taking ticagrelor who received intravenous alteplase at a comprehensive stroke center from January 2016 to December 2019. We then performed a literature search to capture all known published cases of intravenous thrombolysis in stroke patients on ticagrelor. RESULTS: Of the 3896 patients who were treated for AIS at our local comprehensive stroke center during this time period, two patients received intravenous alteplase while on ticagrelor. Both patients had posterior circulation acute strokes and were successfully treated with intravenous alteplase without a systemic or intracranial bleeding event. Only five other cases of intravenous thrombolysis in AIS patients on ticagrelor have been reported in the literature. Among these cases, four of the five cases had a hemorrhagic complication. CONCLUSION: Despite prior reports of hemorrhagic complications with use of IV alteplase in setting of pre-treatment with ticagrelor, we report the safe use of intravenous thrombolysis in two cases presenting with acute ischemic stroke. Until safety is established in large studies, decision for thrombolysis should be made on case-by-case basis.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Terapia Trombolítica , Ticagrelor/administração & dosagem , Ativador de Plasminogênio Tecidual/administração & dosagem , Síndrome Coronariana Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Medição de Risco , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Ticagrelor/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
4.
JAMA ; 324(16): 1640-1650, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107944

RESUMO

Importance: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention. Objective: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice. Design, Setting, and Participants: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019. Exposures: Ticagrelor vs clopidogrel. Main Outcomes and Measures: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis. Results: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group. Conclusions and Relevance: Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Clopidogrel/efeitos adversos , Intervenção Coronária Percutânea , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Aspirina/administração & dosagem , Estudos de Casos e Controles , Causas de Morte , Clopidogrel/administração & dosagem , Bases de Dados Factuais/estatística & dados numéricos , Dispneia/induzido quimicamente , Feminino , Hemorragia/induzido quimicamente , Humanos , Isquemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Metanálise em Rede , Pontuação de Propensão , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Recidiva , República da Coreia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Ticagrelor/administração & dosagem , Estados Unidos
5.
JAMA ; 324(8): 761-771, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32840598

RESUMO

Importance: After percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown. Objective: To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI. Design, Setting, and Participants: Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019. Interventions: Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months. Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50. Results: Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16). Conclusions and Relevance: Among CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01742117.


Assuntos
Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/genética , Inibidores do Citocromo P-450 CYP2C19/uso terapêutico , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea/efeitos adversos , Medicina de Precisão , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/cirurgia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/terapia , Inibidores do Citocromo P-450 CYP2C19/efeitos adversos , Feminino , Genótipo , Técnicas de Genotipagem , Hemorragia/induzido quimicamente , Heterozigoto , Humanos , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Testes Imediatos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos
6.
Kardiologiia ; 60(6): 867, 2020 Jul 07.
Artigo em Russo | MEDLINE | ID: mdl-32720622

RESUMO

Aim      To compare hemorrhagic safety of ticagrelor and clopidogrel in patients with ST-segment elevation acute coronary syndrome (STEACS) after thrombolytic therapy (TLT).Material and methods  This nonrandomized study included 183 patients followed up for 30 days. Hemorrhagic safety was compared in a group of patients with STEACS (n=71) after a thrombolytic treatment with alteplase and early ticagrelor treatment (180 mg followed by switching to 90 mg twice daily) and in a group of patients (n=112) with STEACS receiving TLT with alteplase and clopidogrel (loading dose, 600 mg followed by switching to 75 mg daily). Primary endpoint was hemorrhage associated with TLT; patients were followed up for 30 days.Results During the follow-up period, TLT-associated hemorrhages were observed in 11.3% of patients in the ticagrelor treatment group and in 10.7% of patients in the clopidogrel treatment group (p=0.9; odds ratio, 1.06 at 95 % confidence interval, from 0.41 to 2.73). Intracranial hemorrhages and fatal hemorrhages were absent in both groups.Conclusion      There were no significant differences in hemorrhagic safety between patients with STEACS after the TLT treatment with alteplase and early treatment with ticagrelor or clopidogrel.


Assuntos
Síndrome Coronariana Aguda , Hemorragia/induzido quimicamente , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento
7.
Aliment Pharmacol Ther ; 52(4): 646-654, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32657466

RESUMO

BACKGROUND: Gastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood. AIM: To compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees . METHODS: Propensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1-year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH). RESULTS: We identified 37 019 patients with ACS (non-ST elevation ACS [NSTE-ACS] and ST-elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54-0.81) in GIB overall and with NSTE-ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42-0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64-0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49-0.85) in STEMI patients but no reduction of GIB risk in NSTE-ACS patients. CONCLUSIONS: In the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Clopidogrel/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/efeitos adversos , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/epidemiologia , Idoso , Clopidogrel/uso terapêutico , Estudos de Coortes , Feminino , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Cloridrato de Prasugrel/uso terapêutico , Estudos Retrospectivos , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Ticagrelor/uso terapêutico , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
J Cardiothorac Surg ; 15(1): 155, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600365

RESUMO

BACKGROUND: Coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) can be the only option for complete revascularization in some patients with diffuse coronary artery disease. Unfortunately, CE can cause the lack of endothelium, resulting in increased risk of thrombotic events. Therefore, antithrombotic therapy is very important after surgery. However, there's no consistent protocol exists till now. The aim of this study was to compare the effectiveness and safety of dual antiplatelet therapies (DAPT) including aspirin plus clopidogrel (AC) or ticagrelor (AT) after CE + CABG. METHOD: A total of 137 continuous patients (mean age 60.0 ± 9.0 years) underwent CE + CABG from January 2016 to July 2018 in our center, and patients who received dual antiplatelet therapy (DAPT) after surgery (n = 121) were included in this study. All of the patients received aspirin 100 mg daily therapy after surgery, and 67 of the patients received extra clopidogrel 75 mg (AC) daily therapy, whereas 54 received extra ticagrelor 90 mg (AT) twice daily. All patients continued aspirin monotherapy after 1 year. Occurrence of ischemic events and bleeding events between two groups were compared. Kaplan-Meier survival was used to compare freedom from major adverse cardiovascular and cerebrovascular events (MACCE) between two groups, and log-rank test was used to confirm statistical difference. RESULTS: Follow-up was completed by 99.2%, and median follow-up time was 30.0(22.5, 35.2) months. No operative death was observed, while perioperative myocardial infarction was observed in 2(1.7%) patients (AC 1.5% vs. AT 1.9%, p = ns). One patient in AC group suffered from cardiac tamponade. During the follow-up period, no death was observed. Ischemic events including nonfatal myocardial infarction, repeat revascularization and ischemic stroke were observed in 6(5.0%) patients (AC 4.5% vs. AT 5.6%, p = ns). Overt bleeding had occurred in 3(2.5%) patients (AC 3.0% vs. AT 1.9%, p = ns). Kaplan-Meier analysis indicated that MACCE-free survival of the two groups at 3 years was 97.0% in the AC group versus 94.1% in the AT group (p = ns). CONCLUSION: In patients undergoing CE + CABG, DAPT therapy can be effective and safe with comparable results between AC and AT therapy in terms of ischemic and bleeding events. Further studies are needed.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla , Endarterectomia , Idoso , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Estudos de Coortes , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Terapia Antiplaquetária Dupla/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/induzido quimicamente , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Resultado do Tratamento
9.
N Engl J Med ; 383(3): 207-217, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32668111

RESUMO

BACKGROUND: Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied. METHODS: We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding. RESULTS: A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001). CONCLUSIONS: Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).


Assuntos
Aspirina/uso terapêutico , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Avaliação da Deficiência , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Ataque Isquêmico Transitório/complicações , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Prevenção Secundária , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos
10.
Cardiovasc Drugs Ther ; 34(5): 677-684, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32572652

RESUMO

PURPOSE: To compare the effect of ticagrelor with clopidogrel in reducing the risk of ischemic cardiovascular events in patients with late or very late stent thrombosis (LST/VLST) after primary percutaneous coronary intervention (PCI). METHODS: A total of 4538 patients with acute coronary syndrome were screened for angiographically determined LST/VLST. Two hundred and forty-one patients were included in the analysis and grouped according to ticagrelor (n = 81) or clopidogrel (n = 160) at discharge. The clinical outcome was major adverse cardiovascular events (MACE) defined as death, myocardial infarction (MI), ischemic stroke, and revascularization during the 1-yr follow-up period. RESULTS: After propensity score matching, 65 pairs were generated. The incidence of MACE was significantly lower in the ticagrelor group compared with the clopidogrel group (9.3% vs. 21.5%, log-rank p = 0.048). However, no difference was observed in event rates of death, MI, ischemic stroke, and revascularization between the ticagrelor group and the clopidogrel group. CONCLUSION: Following successful primary PCI, patients with LST/VLST who received ticagrelor had fewer ischemic cardiovascular events at 1-yr follow-up, compared with those who received clopidogrel.


Assuntos
Síndrome Coronariana Aguda/terapia , Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Stents , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Clopidogrel/efeitos adversos , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
11.
EuroIntervention ; 16(8): 627-633, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32482616

RESUMO

AIMS: The aim of this study was to investigate the effect of ticagrelor monotherapy after one-month dual antiplatelet therapy (DAPT) or conventional DAPT in patients with or without acute coronary syndrome (ACS) in the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY). METHODS AND RESULTS: Risk estimates were expressed as rate ratios (RR) with 95% confidence intervals (CI). A total of 3,840 ACS and 3,745 stable ischaemic heart disease (SIHD) patients were included. At two years, rates of the co-primary efficacy endpoint, a composite of death, myocardial infarction, stroke or urgent target vessel revascularisation, were 7.94% in the experimental and 9.68% in the control group (RR 0.82, 95% CI: 0.66-1.01) among ACS patients and 6.31% in the experimental and 7.14% in the control group (RR 0.89, 95% CI: 0.69-1.13) among SIHD patients (pint=0.63). Trends for lower and higher risk of BARC 3 or 5 bleeding with the experimental strategy in ACS (2.27% vs 3.00%, RR 0.76, 95% CI: 0.51-1.12) and SIHD (2.70% vs 1.96%, RR 1.39, 95% CI: 0.91-2.12) patients, respectively, were observed with significant interaction testing (pint=0.039). A net clinical benefit endpoint, the composite of both co-primary study endpoints, favoured the experimental treatment among ACS patients only. CONCLUSIONS: Ticagrelor monotherapy after one-month DAPT provided consistent treatment effects on ischaemic endpoints in patients with or without ACS but only the former experienced a net clinical benefit. ClinicalTrials.gov identifier: NCT03231059.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/uso terapêutico , Quimioterapia Combinada , Humanos , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/efeitos adversos , Resultado do Tratamento
12.
Medicine (Baltimore) ; 99(19): e19969, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384446

RESUMO

Although previous clinical trials demonstrated that ticagrelor could reduce cardiovascular events and mortality versus clopidogrel in patients with acute coronary syndrome (ACS), the real-world evidence of its clinical impacts on East Asian Diabetic population has rarely been investigated.Between November 2013 and June 2015, 1534 patients were recruited into the Acute Coronary Syndrome-Diabetes Mellitus Registry of the Taiwan Society of Cardiology (TSOC ACS-DM registry). After propensity score matching, a total of 730 patients undergoing successful revascularization and discharged on ticagrelor (N = 365) or clopidogrel (N = 365) were analyzed. The primary and secondary endpoints were all-cause mortality and re-hospitalization, respectively. The all-cause death associated with ticagrelor vs clopidogrel was 3.6% vs 7.4% (adjusted hazard ratio (HR) 0.34 [0.15-0.80]; P = .0138) at 24 months. The re-hospitalization rate at 24 months was 38.9% vs 39.2% (P = .3258).For diabetic patients with ACS, ticagrelor provided better survival benefit than clopidogrel without an increase of re-hospitalization in 24 months after successful percutaneous coronary intervention. This study in real-world circumstance provided valuable complementary data to externally validate platelet inhibition and patient outcomes (PLATO) finding especially in Asian diabetic population.


Assuntos
Síndrome Coronariana Aguda , Clopidogrel , Diabetes Mellitus/epidemiologia , Intervenção Coronária Percutânea , Ticagrelor , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Readmissão do Paciente/estatística & dados numéricos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Pontuação de Propensão , Sistema de Registros , Prevenção Secundária/métodos , Prevenção Secundária/estatística & dados numéricos , Taiwan/epidemiologia , Ticagrelor/administração & dosagem , Ticagrelor/efeitos adversos , Resultado do Tratamento
13.
PLoS One ; 15(5): e0232768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365100

RESUMO

BACKGROUND: Intensive care unit (ICU) patients with the most severe forms of acute coronary syndrome (ACS) require invasive therapies such as extracorporeal life support. The risk of bleeding in ICU patients with ACS treated with a dual antiplatelet therapy of aspirin and ticagrelor is unknown. The primary objective of this study was to compare the bleeding risk of ticagrelor and clopidogrel in ICU patients with ACS. METHODS AND FINDINGS: We conducted a retrospective study based on a propensity score and a proportional hazards model. All patients with ACS hospitalized in the ICU of a French university hospital between January 2013 and January 2017 were included in the study. Bleeding during ICU stay was defined as all Thrombolysis in myocardial infarction (TIMI) major or minor events. A total of 155 patients were included in the study. According to propensity score matching, 57 patients treated with aspirin and ticagrelor were matched with 57 patients treated with aspirin and clopidogrel. Median (first-third quartile) Simplified Acute Physiology Score II was 61.5 (41.0-85.0). Bleeding during ICU stay occurred in 12 patients (21.1%) treated with clopidogrel and in 35 patients (61.4%) treated with ticagrelor (p<0.0001). This significant association was found for both TIMI major bleeding (12.3% vs. 35.1%, p = 0.004) and TIMI minor bleeding (8.8% vs. 26.3%, p = 0.01). The relative risk of bleeding occurrence during ICU stay was 2.60 (confidence interval 95%: 1.55-4.35) for ticagrelor compared to clopidogrel. No significant difference in ICU mortality was found between the two groups (45.6% in the clopidogrel group vs. 29.8% in the ticagrelor group, p = 0.08). CONCLUSIONS: Bleeding complications are frequent and serious in ICU patients with ACS. A dual antiplatelet therapy of aspirin and ticagrelor is associated with a higher risk of bleeding compared to a dual antiplatelet therapy of aspirin and clopidogrel.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Hemorragia/induzido quimicamente , Unidades de Terapia Intensiva , Pontuação de Propensão , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Fatores de Risco , Resultado do Tratamento
14.
Am Heart J ; 225: 19-26, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32473355

RESUMO

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.


Assuntos
Síndrome Coronariana Aguda/terapia , Clopidogrel/uso terapêutico , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Insuficiência Renal Crônica/complicações , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/prevenção & controle , Adolescente , Adulto , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Prevenção Secundária , Trombose/prevenção & controle , Ticagrelor/efeitos adversos , Adulto Jovem
16.
Lancet ; 395(10233): 1374-1381, 2020 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334703

RESUMO

BACKGROUND: Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013-001403-37). FINDINGS: Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference -4%, 95% CI -10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35). INTERPRETATION: In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk. FUNDING: ZonMw.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/efeitos adversos , Feminino , Humanos , Masculino , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos
18.
BMC Cardiovasc Disord ; 20(1): 109, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138662

RESUMO

BACKGROUND: Patients with coronary chronic total occlusion (CTO) require effective antiplatelet therapy after percutaneous coronary intervention (PCI). Ticagrelor has more pronounced platelet inhibition than clopidogrel. However, the most appropriate dose of ticagrelor in East Asian populations remains unclear. METHOD: We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter and 120 mg loading dose, 60 mg twice daily thereafter) and clopidogrel (300 mg loading dose, 75 mg daily thereafter) for prevention of cardiovascular events in 525patients with CTO undergoing PCI. RESULTS: The rate of in-hospital major adverse cardiac and cerebral events (MACCE) was not different between the groups. At 1-year follow-up, target vessel revascularization (TVR) in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.047); TVR was significantly decreased in 60 mg ticagrelor compared to standard dose clopidogrel (p = 0.046). At 1-year follow-up, overall MACCE in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.023). Kaplan-Meier analysis showed MACCE-free survival was significantly higher in both ticagrelor groups than in the clopidogrel group (p = 0.024). During hospitalization, minor bleeding was significant increased in the 90 mg ticagrelor group (p = 0.021). At 1-year follow-up, risk of major and minor bleeding were significantly increased in the 90 mg ticagrelor group. CONCLUSION: In East Asian patients with CTO undergoing PCI, 60 mg ticagrelor was as effective as 90 mg, at the same time significantly reduced risk of bleeding.


Assuntos
Clopidogrel/administração & dosagem , Oclusão Coronária/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Ticagrelor/administração & dosagem , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Doença Crônica , Clopidogrel/efeitos adversos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/etnologia , Oclusão Coronária/mortalidade , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
19.
J Gastroenterol Hepatol ; 35(10): 1720-1730, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32154936

RESUMO

BACKGROUND AND AIM: The presence and severity of upper gastrointestinal mucosal lesions have not been evaluated using esophagogastroduodenoscopy (EGD) in patients receiving ticagrelor plus aspirin or alone after myocardial revascularization. We assessed upper gastrointestinal mucosal injury and the use of proton pump inhibitors (PPIs) in patients receiving 1 year of antiplatelet therapy after coronary artery bypass grafting (CABG). METHODS: In this single-center prospective substudy of a randomized trial, 231 patients completing 1-year antiplatelet therapy (ticagrelor 90 mg twice daily plus aspirin 100 mg once daily, ticagrelor 90 mg twice daily, or aspirin 100 mg once daily, in 81, 80, and 70 patients, respectively) after CABG underwent 13 C urea breath testing and EGD. Gastroduodenal lesions were assessed by modified Lanza score, and reflux esophagitis was evaluated according to Los Angeles classification. Additionally, at least one ulcer ≥ 5 mm was separately analyzed. RESULTS: Among 231 patients, EGD showed 28 (12.1%) with ulcers ≥ 5 mm, which were detected in 13.6% (11/81) of ticagrelor plus aspirin recipients, 8.8% (7/80) of ticagrelor recipients, and 14.3% (10/70) of aspirin recipients, and 24 (10.4%) had reflux esophagitis. Eighty-eight (38.1%) patients had a positive 13 C urea breath testing after 1 year of treatment, and one patient received eradication therapy during follow up. Nineteen (8.2%) patients received a PPI for ≥ 6 months. CONCLUSIONS: Severe upper gastrointestinal mucosal lesions were more frequently observed in patients treated with ticagrelor plus aspirin and aspirin monotherapy than in patients treated with ticagrelor monotherapy for 1 year post-CABG. Prophylactic use of PPIs might be inadequate.


Assuntos
Aspirina/efeitos adversos , Ponte de Artéria Coronária , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Ticagrelor/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/patologia , Síndrome Coronariana Aguda/cirurgia , Idoso , Aspirina/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Estudos Prospectivos , Inibidores da Bomba de Prótons/administração & dosagem , Úlcera Gástrica/prevenção & controle , Ticagrelor/administração & dosagem , Fatores de Tempo
20.
BMC Cardiovasc Disord ; 20(1): 140, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183711

RESUMO

BACKGROUND: Ticagrelor and prasugrel are two third-generation oral P2Y12 inhibitors which are more commonly used in clinical practice. However, dyspnea has been consecutively reported in patients using third-generation oral P2Y12 inhibitors. This study aims to compare the risk of dyspnea in patients treated with third-generation P2Y12 inhibitors compared with clopidogrel. METHODS: We systematically searched the PubMed, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov and Web of Science for randomized control trials (RCTs) comparing ticagrelor or prasugrel with clopidogrel until July 2019. The primary outcome was the incidence of dyspnea. The risk ratios (RR) and 95% confidence intervals (CI) were estimated using meta-analysis. RESULTS: We included 25 RCTs involving 63,484 patients in this meta-analysis, including 21 studies on ticagrelor and 4 studies on prasugrel. Compared to the clopidogrel group, third-generation oral P2Y12 inhibitors were associated with an increased risk of dyspnea compared with clopidogrel (RR 2.15, 95% CI 1.59-2.92), which was consistent in the analysis of ticagrelor (RR 2.65, 95% CI 1.87-3.76). However, the adverse effect was not found among patients receiving prasugrel therapy (RR 1.03, 95% CI 0.86-1.22). The increased dyspnea risk of ticagrelor was consistent in subgroups with different follow-up durations (≤ 1 month RR 1.87, 95% CI 1.56-2.24; 1-6 months RR 4.19, 95% CI 1.99-8.86; > 6 months 2.45, 95% CI 1.13-5.34). CONCLUSIONS: Ticagrelor has a higher risk of dyspnea than clopidogrel, which was not observed in patients using prasugrel.


Assuntos
Clopidogrel/efeitos adversos , Dispneia/induzido quimicamente , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dispneia/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Adulto Jovem
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