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3.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(2): 170-175, 2021 Feb 24.
Artigo em Chinês | MEDLINE | ID: mdl-33611904

RESUMO

Objectives: To compare the impact of ticagrelor or clopidogrel on serum uric acid levels among patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) and further evaluate the effects of variation of serum uric acid levels on platelet reactivity. Methods: STEMI patients who admitted to Fuwai Hospital from April 2017 to January 2020, and underwent primary PCI and discharged alive with aspirin and ticagrelor or clopidogrel were included in this study. Patients were divided into ticagrelor group and clopidogrel group. The baseline clinical data were collected. Serum uric acid and creatinine levels at baseline and 30 days post-PCI were measured. Light transmittance aggregometry was used to assess maximum aggregation rate induced by adenosine diphosphate and arachidonic acid. The changes of serum uric acid and creatinine were compared between the two groups. Multivariate logistic regression was performed to evaluate independent related factors for rise in the uric acid levels, and the effect of variation of serum uric acid level on platelet reactivity was analyzed. Results: A total of 967 patients were included, the age was (59.4±12.1) years, and 163 case were female. There were 550 cases in ticagrelor group (56.9%) and 417 cases in clopidogrel group (43.1%). Baseline serum uric acid and creatinine levels were similar between the 2 groups. At 30 days, the serum uric acid level [(347.2±96.5) mmol/L vs. (341.2±105.3) mmol/L, P=0.009] and absolute [46.4 (-2.4, 88.1) mmol/L vs. 25.0 (-21.9, 73.0) mmol/L, P=0.001] and percentage [13.2 (-0.01, 29.0) % vs. 7.9 (-5.7, 25.0) %, P=0.007] increase in the serum uric acid levels were significantly higher in ticagrelor group than in clopidogrel group. The level of serum creatinine at 30 days was significantly lower in ticagrelor group than in clopidogrel group [(89.7±21.3) µmol/L vs. (94.4±43.9) µmol/L, P<0.05], whereas there were no differences in absolute [8.0 (-1.4, 16.6) µmol/L vs. 7.8 (-2.0, 16.6) µmol/L] and percentage [10.5 (-1.7%, 22.6%) vs. 9.8 (-2.4%, 22.1%)] change in the serum creatinine between the 2 groups (all P>0.05). Logistic regression analysis showed that, after adjusting for confounding factors, ticagrelor therapy was an independent related factor of serum uric acid elevation (OR=1.582, 95% CI:1.023-2.447, P=0.039). The variation of the serum uric acid levels did not affect platelet aggregation and the percentage of high platelet reactivity in both groups. Conclusions: Ticagrelor use is related to a significant increase in the serum uric acid levels at 30 days post-PCI in this patient cohort. The variations in the uric acid levels do not increase the percentage of high platelet reactivity in STEMI patients treated with ticagrelor or clopidogrel.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Adenosina/uso terapêutico , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Ticlopidina , Fatores de Tempo , Resultado do Tratamento , Ácido Úrico
5.
Int Heart J ; 62(1): 171-174, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33455983

RESUMO

A 41-year-old woman with chest pain for 6 hours was admitted to our chest pain center, presenting with acute myocardial infarction. Coronary angiography showed acute total occlusion in the proximal left anterior descending artery due to late stent thrombosis. After thrombus aspiration and intracoronary administration of 0.5 mg tirofiban, repeated angiography showed that no obvious residual stenosis remained. The patient underwent drug-coated balloon angioplasty 69 days ago and was then administered dual antiplatelet treatment (aspirin and clopidogrel) uninterruptedly. Genetic testing found that both cytochrome P450 2C19 (CYP2C19) (G681A) and glycoprotein Ia (GPIa) (C807T, G873A) were hybrid mutant types, demonstrating that the patient was possibly resistant to clopidogrel and aspirin simultaneously. Thus, clopidogrel was replaced by ticagrelor and no more cardiovascular adverse events occurred during the 2-year follow-up.


Assuntos
Oclusão Coronária/etiologia , Reestenose Coronária/etiologia , Infarto do Miocárdio/diagnóstico , Doença Aguda , Adulto , Assistência ao Convalescente , Angioplastia Coronária com Balão/métodos , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Clopidogrel/uso terapêutico , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Reestenose Coronária/terapia , Citocromo P-450 CYP2C19/genética , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/métodos , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Humanos , Integrina alfa2/genética , Mutação/genética , Infarto do Miocárdio/etiologia , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Stents/efeitos adversos , Trombectomia/métodos , Trombose/terapia , Ticagrelor/administração & dosagem , Ticagrelor/uso terapêutico , Tirofibana/administração & dosagem , Tirofibana/uso terapêutico , Resultado do Tratamento
6.
J Clin Neurosci ; 82(Pt A): 128-133, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33317720

RESUMO

PURPOSE: To reduce procedural thromboembolisms, tailored antiplatelet drug preparation has been used according to antiplatelet resistance for endovascular coiling of unruptured aneurysms. We compared an aspirin plus clopidogrel group with a ticagrelor group using diffusion-weighted imaging (DWI) after stent-assisted coiling for unruptured aneurysms. METHODS: From October 2018 to April 2019, 72 patients with 78 aneurysms underwent stent-assisted coiling, with aspirin plus clopidogrel (n = 20 patients with 22 aneurysms) or ticagrelor (n = 52 patients with 56 aneurysms) as an antiplatelet preparation, and were enrolled in our study. All patients were evaluated using DWI 2 h after coiling to detect procedural thromboembolisms. RESULTS: Postprocedure infarction was observed on DWI in 37 procedures (47.4%), and symptomatic infarction occurred in 1 procedure (1.28%). Postprocedure infarction was significantly lower in the aspirin plus clopidogrel than in ticagrelor group (27.3% vs. 55.4%, p = 0.043). Postprocedure infarction was associated with aneurysm type (sidewall aneurysm (30.8%) vs. aneurysm with incorporated branches (64.1%), p = 0.006) and guiding catheter type (single (23.8%) vs. double (56.1%), p = 0.020). Multivariable logistic regression analysis demonstrated that postprocedure infarction was related to aneurysm type (adjusted odds ratio (OR); 3.317, confidence interval (CI); 1.223-8.991, p = 0.018), guiding catheter type (adjusted OR; 2.783, CI; 0.828-9.353, p = 0.098), and antiplatelet medication (adjusted OR; 1.295, CI; 0.969-1.730, p = 0.080). CONCLUSIONS: Postprocedure infarction was observed on DWI after stent-assisted coiling for unruptured aneurysms more frequently in the ticagrelor group than in the aspirin plus clopidogrel group. However, our study suggests that postprocedure infarction is more associated with aneurysm type than antiplatelet medication.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Tromboembolia/tratamento farmacológico , Ticagrelor/uso terapêutico , Adulto , Idoso , Imagem de Difusão por Ressonância Magnética , Embolização Terapêutica , Feminino , Humanos , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Stents
7.
Medicine (Baltimore) ; 99(45): e22600, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157917

RESUMO

BACKGROUND: This study will assess the efficacy and safety of ticagrelor in the treatment of patients with stable coronary heart disease (SCHD). METHODS: We will search the following databases for relevant potential studies in Cochrane Library, MEDLINE, EMBASE, Web of Science, Google Scholar, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will search all literature sources from inception to the present without limitations of language and publication status. We will only consider randomized controlled trials on exploring the efficacy and safety of ticagrelor for the treatment of SCHD. Investigators will separately examine studies, collect data and appraise study quality. Data synthesis and analysis will be performed using RevMan 5.3 software. RESULTS: This study will summarize high quality synthesis of present evidence of ticagrelor for the treatment of SCHD. CONCLUSION: The findings of this study will provide evidence to appraise whether ticagrelor is effective for the treatment of patients with SCHD. OSF REGISTRATION NUMBER:: osf.io/fq69u.


Assuntos
Doença das Coronárias/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Projetos de Pesquisa , Ticagrelor/uso terapêutico , Humanos , Revisões Sistemáticas como Assunto
10.
Am J Cardiol ; 132: 22-28, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771221

RESUMO

Prasugrel and ticagrelor are preferred over clopidogrel for patients with acute coronary syndrome who underwent percutaneous coronary intervention. We sought to determine the relative merits of 1 agent over the other. Multiple databases were queried to identify relevant randomized control trials (RCTs) and observational cohort studies. Random-effects model was used to calculate an unadjusted odds ratio (OR) for major adverse cardiovascular and cerbrovascular events (MACCE) and its components. A total of 27 (7 RCTs, 20 observational cohort studies) studies comprising 118,266 (prasugrel 62,716, ticagrelor 51,196) patients were included. At 30 days, prasugrel was associated with a significantly lower odds of MACCE (OR 0.75, 95% confidence interval [CI] 0.67 to 0.85, p ≤0.0001) and mortality (OR 0.65, 95% CI 0.59 to 0.71, p ≤0.0001). At 1 year, the overall odds of mortality favored prasugrel (OR 0.79, 95% CI 0.68 to 0.92, p = 0.002), but no significant interdrug difference was seen in terms of MACCE (OR 0.89, 95% CI 0.76 to 1.05, p = 0.16). There was no significant difference in the odds of overall myocardial infarction, revascularization, stent thrombosis, stroke, and major bleeding events between the 2 groups on both 30-day and 1-year follow-up. A subgroup analysis of RCTs data showed no significant difference between prasugrel and ticagrelor in terms of any end point at all time points. In conclusion, prasugrel might have lower odds of MACCE and mortality at 30 days. However, there was no difference in the safety and efficacy end points of 2 drugs at 1 year. The observed transient prasugrel-related mortality benefits were subject to the bias of nonrandomized assignment.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Cloridrato de Prasugrel/uso terapêutico , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/cirurgia , Quimioterapia Combinada , Saúde Global , Humanos , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Taxa de Sobrevida/tendências
11.
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
12.
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
13.
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
14.
Am J Cardiol ; 130: 56-63, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32680674

RESUMO

In light of recent studies describing the antibacterial properties of ticagrelor, the association between treatment with ticagrelor and subsequent risk for infection following acute coronary syndrome (ACS) is taking on increased importance. A single center, retrospective, matched cohort analysis was performed. All patients older than 30 years of age admitted between January 1, 2013 and November 1, 2019 for an ACS and discharged with dual antiplatelet therapy (DAPT) were included. The primary outcome was defined as hospital admissions due to infections likely caused by gram-positive bacteria up to 1 year following the ACS hospitalization. The base cohort included 3,909 patients. About 2,035 (52.1%) were treated with ticagrelor and 1,874 (47.9%) with clopidogrel. Patients treated with ticagrelor had a 64% lower risk of gram-positive infection during the first year following hospitalization after adjusting for demographic and co-morbidity factors compared with those treated with clopidogrel (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21 to 0.61; p <0.001). In a cohort starting from 1 year (conclusion of DAPT period) and up to 3 years following ACS hospitalization, the risk of gram-positive infection was comparable in both groups (HR, 0.70; 95% CI, 0.41 to 1.19; p = 0.182). Treatment with ticagrelor was not associated with a reduced risk of gram-negative infections (HR, 0.48; 95% CI, 0.21 to 1.06; p = 0.07). In conclusion, DAPT regimen that includes aspirin and ticagrelor is associated with reduced risk of gram-positive infection compared with the combination of aspirin and clopidogrel.


Assuntos
Síndrome Coronariana Aguda/complicações , Infecções por Bactérias Gram-Positivas/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/uso terapêutico , Estudos de Coortes , Feminino , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
15.
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
16.
Brasília; s.n; 24 jul. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117704

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 21 artigos e 15 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Metilprednisolona/uso terapêutico , Vacinas/uso terapêutico , Heparina/uso terapêutico , Estudos de Coortes , Azitromicina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Células-Tronco Mesenquimais , Darunavir/uso terapêutico , Adalimumab/uso terapêutico , Rituximab/uso terapêutico , Infliximab/uso terapêutico , Clopidogrel/uso terapêutico , Ticagrelor/uso terapêutico , Hidroxicloroquina/uso terapêutico , Anticoagulantes/uso terapêutico
17.
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
18.
Lancet ; 395(10235): 1487-1495, 2020 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386592

RESUMO

BACKGROUND: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS: In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION: Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING: Italian Ministry of Education.


Assuntos
Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Clopidogrel/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Ticlopidina/uso terapêutico , Idoso , Aterosclerose/complicações , Transtornos Cerebrovasculares/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle
19.
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
20.
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
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