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1.
BMC Neurol ; 21(1): 409, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702218

RESUMO

AIM: Insulin resistance was reported to increase the risk of ischemic stroke, which can be assessed by the triglyceride glucose (TyG) index. However, it remains unclear whether the TyG index influences the platelet reactivity during the treatment of ischemic patients. METHODS: Ischemic stroke patients receiving dual antiplatelet therapy (DAPT) within 48 h onset were consecutively included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The top quartile of TyG index was defined as insulin resistance. The platelet reactivity was assessed by thromboelastography. The platelet inhibition rate induced by arachidonic acid (AA) or adenosine diphosphate (ADP) was used to confirm the high residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel, respectively. The association between TyG index and platelet reactivity was assessed by Kruskal-Wallis test. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. RESULTS: A total of 1002 patients were included and divided into 4 groups by quartiles of the TyG index (< 2.02; 2.02-2.27; 2.27-2.52; ≥2.52). The findings demonstrated that the maximum intensity of the clot increased, but the AA-induced platelet inhibition rate decreased, depending on the TyG index quartiles. No significant difference was found in the ADP-induced platelet inhibition rate among groups. The prevalence of aspirin HRPR increased depending on the TyG index quartile. Unlike the non-insulin resistance group, the insulin resistance group was independently associated with aspirin HRPR (OR = 1.689, 95% CI 1.14 to 2.51, P = 0.009). CONCLUSIONS: In acute ischemic stroke patients taking DAPT, the elevation of the TyG index is associated with enhanced platelet reactivity and higher prevalence of aspirin HRPR. Insulin resistance assessed by the TyG index could be an independent risk factor for aspirin HRPR.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Glucose , Humanos , Agregação Plaquetária , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/farmacologia , Ticlopidina , Triglicerídeos
2.
Rev Cardiovasc Med ; 22(3): 975-981, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565098

RESUMO

There is limited data about the bleeding complication of antiplatelet therapy after coronary artery bypass graft (CABG) operations focused on diabetic patients. Herein, we aimed to evaluate the effects of aspirin and clopidogrel monotherapies on postoperative bleeding in these patients. A total of 165 diabetic patients who underwent isolated off-pump beating heart coronary artery bypass (OPCAB) operation were evaluated, 84 patients were included in this retrospective study. Patients were divided into groups according to the type of antiplatelet regime. Chest tube drainage amounts and the amount of blood product transfusions were evaluated. Acetylsalicylic acid (ASA) - group included 42 aspirin monotherapy and Clopidogrel - group included 42 clopidogrel monotherapy patients after propensity matching. The mean drainage amount in ASA - group was 670.24 ± 185.46 mL, in Clopidogrel - group was 921.43 ± 167.53 mL (p < 0.001). More packed red blood cell (PRBC) and fresh frozen plasma (FFP) units were needed in the Clopidogrel - group than in the ASA - group (2.05 ± 1.13 vs. 0.83 ± 0.93 units of PRBC, and 1.90 ± 0.58 vs. 1.05 ± 0.58 units of FFP, respectively, p < 0.001). In conclusion, clopidogrel had a stronger effect on bleeding in diabetic patients than aspirin after OPCAB surgery.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Diabetes Mellitus , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Ticlopidina/efeitos adversos
4.
Chin Med J (Engl) ; 134(14): 1720-1725, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34267067

RESUMO

BACKGROUND: Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal. METHODS: Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued <5 days before surgery constituted the clopidogrel group. The control group constituted 60 patients not taking antiplatelet or anticoagulant drugs and matched 1:1 with the clopidogrel group for sex, fracture type, operative procedure, and time from injury to operation (±10 h). The primary outcome was perioperative blood loss and the secondary outcomes were transfusion requirement, complications, and mortality. The Student's t test or Wilcoxon signed rank sum test was used for continuous variables and the Chi-square test was used for categorical variables. RESULTS: Age, body mass index, American Society of Anesthesiologists score, and percentage undergoing general anesthesia were comparable between the groups (P > 0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P < 0.001) and cerebrovascular disease (45.0% vs. 15.0%; P < 0.010) were significantly higher in the clopidogrel vs. control groups, respectively. The median clopidogrel discontinuation time before operation was 73.0 (range: 3.0-120.0) h. There was no significant difference in the estimated perioperative blood loss between the clopidogrel group (median: 745 mL) and control group (median: 772 mL) (P = 0.866). The intra-operative transfusion rate was higher in the clopidogrel group (22/60, 36.7%) than that in the control group (12/60, 20.0%) (P < 0.050). However, there was no significant difference in the blood transfusion rate during the entire perioperative period (26/60, 43.3% vs. 20/60, 33.3%; clopidogrel group vs. control group, respectively; P > 0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups. CONCLUSIONS: Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.


Assuntos
Fraturas do Quadril , Ticlopidina , Idoso , Estudos de Casos e Controles , Clopidogrel/uso terapêutico , Fraturas do Quadril/tratamento farmacológico , Fraturas do Quadril/cirurgia , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Ticlopidina/efeitos adversos
5.
Cochrane Database Syst Rev ; 7: CD002786, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34298589

RESUMO

BACKGROUND: People with end-stage renal disease (ESRD) often require either the formation of an arteriovenous fistula (AVF) or an interposition prosthetic arteriovenous graft (AVG) for haemodialysis. These access sites should ideally have a long life and a low rate of complications (e.g. thrombosis, infection, stenosis, aneurysm formation and distal limb ischaemia). Although some of the complications may be unavoidable, any adjuvant technique or medical treatment aimed at decreasing complications would be welcome. This is the fourth update of the review first published in 2003. OBJECTIVES: To assess the effects of adjuvant drug treatment in people with ESRD on haemodialysis via autologous AVFs or prosthetic interposition AVGs. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and ClinicalTrials.gov trials register to 6 August 2020. SELECTION CRITERIA: Randomised controlled trials of active drug versus placebo in people with ESRD undergoing haemodialysis via an AVF or prosthetic interposition AVG. DATA COLLECTION AND ANALYSIS: For this update, two review authors (IM, MFAK) independently selected trials for inclusion, extracted data, assessed risk of bias and assessed the certainty of the evidence according to GRADE. We resolved disagreements by discussion or consultation with another review author (ADS). The primary outcome was the long-term fistula or graft patency rate. Secondary outcomes included duration of hospital stay; complications such as infection, aneurysm formation, stenosis and distal limb ischaemia; and number of related surgical or radiological interventions. MAIN RESULTS: For this update, one additional study was suitable for inclusion, making a total of 13 trials with 2080 participants. Overall the certainty of the evidence was low or moderate due to short follow-up periods, heterogeneity between trials, small sample sizes, and risk of bias due to incomplete reporting. Medical adjuvant treatments used in the included trials were aspirin, ticlopidine, dipyridamole, dipyridamole plus aspirin, warfarin, fish oil, clopidogrel, sulphinpyrazone and glyceryl trinitrate (GTN) patch.  All included studies reported on graft patency by measuring graft thrombosis. There was insufficient evidence to determine if there was a difference in graft patency in studies comparing aspirin versus placebo (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.07 to 2.25; 3 studies, 175 participants; low-certainty evidence). The meta-analysis for graft patency comparing ticlopidine versus placebo favoured ticlopidine (OR 0.45, 95% CI 0.25 to 0.82; 3 studies, 339 participants; moderate-certainty evidence). There was insufficient evidence to determine if there was a difference in graft patency in studies comparing fish oil versus placebo (OR 0.24, 95% CI 0.03 to 1.95; 2 studies, 220 participants; low-certainty evidence); and studies comparing clopidogrel and placebo (OR 0.40, 95% CI 0.13 to 1.19; 2 studies, 959 participants; moderate-certainty evidence). Similarly, there was insufficient evidence to determine if there was a difference in graft patency comparing the effect of dipyridamole versus placebo (OR 0.46, 95% CI 0.11 to 1.94; 1 study, 42 participants, moderate-certainty evidence) and dipyridamole plus aspirin versus placebo (OR 0.64, CI 0.16 to 2.56; 1 study, 41 participants; moderate-certainty evidence); comparing low-intensity warfarin with placebo (OR 1.76, 95% CI 0.78 to 3.99; 1 study, 107 participants; low-certainty evidence); comparing sulphinpyrazone versus placebo (OR 0.43, 95% CI 0.03 to 5.98; 1 study, 16 participants; low-certainty evidence) and comparing GTN patch and placebo (OR 1.26, 95% CI 0.63 to 2.54; 1 study, 167 participants; moderate-certainty evidence). The single trial evaluating warfarin was terminated early because of major bleeding events in the warfarin group. Only two studies published data on the secondary outcome of related interventions (surgical or radiological); there was insufficient evidence to determine if there was a difference in related interventions between placebo and treatment groups. None of the included studies reported on the duration of hospital stay.  Most studies reported complications ranging from mortality to nausea. However, data on complications were limited and reporting varied between studies. AUTHORS' CONCLUSIONS: The meta-analyses of three studies for ticlopidine (an antiplatelet treatment), which all used the same dose of treatment but with a short follow-up of only one month, suggest ticlopidine may have a beneficial effect as an adjuvant treatment to increase the patency of AVFs and AVGs in the short term. There was insufficient evidence to determine if there was a difference in graft patency between placebo and other treatments such as aspirin, fish oil, clopidogrel, dipyridamole, dipyridamole plus aspirin, warfarin, sulphinpyrazone and GTN patch. The certainty of the evidence was low to moderate due to short follow-up periods, the small number of studies for each comparison, small sample sizes, heterogeneity between trials and risk of bias due to incomplete reporting. Therefore, it appears reasonable to suggest further prospective studies be undertaken to assess the use of these antiplatelet drugs in renal patients with an AVF or AVG.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/métodos , Falência Renal Crônica/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Grau de Desobstrução Vascular/efeitos dos fármacos , Quimioterapia Adjuvante , Óleos de Peixe/uso terapêutico , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/métodos , Ticlopidina/uso terapêutico , Dispositivos de Acesso Vascular
6.
Arch Cardiovasc Dis ; 114(8-9): 577-587, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257048

RESUMO

BACKGROUND: Survivors of out-of-hospital cardiac arrest undergoing percutaneous coronary intervention are at high thrombotic and bleeding risk. The type of antiplatelet that should be used in these patients remains controversial. AIM: To compare the impact of the use of more potent P2Y12 receptor inhibitors on thrombotic and bleeding events with that of clopidogrel in survivors of out-of-hospital cardiac arrest undergoing percutaneous coronary intervention. METHODS: This was an observational study including consecutive patients treated for out-of-hospital cardiac arrest associated with acute coronary syndrome by percutaneous coronary intervention with stent implantation and dual antiplatelet therapy between January 2007 and December 2017. Baseline characteristics, mortality and in-hospital haemorrhagic and thrombotic events were compared between patients who received clopidogrel and those who received more potent P2Y12 receptor inhibitors. RESULTS: Among the 359 included patients, 197 received clopidogrel and 162 received ticagrelor or prasugrel. The primary composite endpoint of death, definite stent thrombosis or major bleeding was similar in the two groups (57.4% in the clopidogrel group vs. 53.7% in the new P2Y12 receptor inhibitors group; P=0.49). Fewer haemorrhagic events occurred in the clopidogrel group (21.8% vs. 31.5%; P=0.04), whereas similar rates of definite stent thrombosis were observed (5.1% vs. 6.2%; P=0.65). The use of more potent P2Y12 receptor inhibitors was an independent predictor of major bleeding (odds ratio 2.69, 95% confidence interval 1.37-5.25; P=0.004). CONCLUSIONS: In this specific population, the use of more potent P2Y12 receptor inhibitors was not associated with a reduced thrombosis rate compared with clopidogrel, but with a higher haemorrhagic risk. Prospective studies should be performed on the optimal antithrombotic therapy in this subset of patients.


Assuntos
Síndrome Coronariana Aguda , Parada Cardíaca Extra-Hospitalar , Intervenção Coronária Percutânea , Trombose , Hemorragia/induzido quimicamente , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Sobreviventes , Ticlopidina , Resultado do Tratamento
9.
Adv Ther ; 38(7): 4026-4039, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34115329

RESUMO

INTRODUCTION: The PLATelet inhibition and patient Outcomes (PLATO) trial (NCT00391872) demonstrated that ticagrelor compared to clopidogrel significantly reduced the rate of death from cardiovascular causes, myocardial infarction or stroke in patients with acute coronary syndrome (ACS). The aim of this study is to analyze the long-term cost-effectiveness of ticagrelor compared to clopidogrel in ACS patients from a Vietnamese healthcare payers' perspective. METHODS: A two-part cost-effectiveness model was developed to estimate long-term costs and quality-adjusted life-years (QALY). Cardiovascular event rates, hospital bed days, interventions, investigations, study drug utilization and EuroQol 5 Dimension (EQ-5D) data were derived from the PLATO trial. Unit costs of medical services were derived from the Vietnamese governmental price list, and drug costs were based on the weighted average price from the Vietnamese social security report (in VND; 10.000 VND = 0.405 USD). An annual discount rate of 3% was used. Probabilistic and deterministic sensitivity analyses were conducted to evaluate uncertainty of the results. RESULTS: Ticagrelor was associated with an incremental cost of VND 5.34 million (USD 216.49) and a QALY gain of 0.11. This resulted in a cost per QALY gained of VND 49.58 million (USD 2009.96) from the Vietnamese healthcare payers' perspective. Probabilistic sensitivity analysis indicates that ticagrelor has 59% probability of being cost-effective compared with clopidogrel when using a willingness-to-pay threshold of one gross domestic products (GDP) per capita. Deterministic sensitivity analysis using clinical outcomes from the Asian sub-population of PLATO resulted in a cost per QALY of VND 42.25 million (USD 1712.80). CONCLUSION: Ticagrelor can be considered a cost-effective treatment for ACS compared with clopidogrel from a Vietnamese healthcare payers' perspective.


Assuntos
Síndrome Coronariana Aguda , Síndrome Coronariana Aguda/tratamento farmacológico , Adenosina , Grupo com Ancestrais do Continente Asiático , Clopidogrel/uso terapêutico , Análise Custo-Benefício , Custos de Medicamentos , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Ticlopidina
11.
Clin Cardiol ; 44(6): 789-796, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33978269

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in patients with acute coronary syndrome (ACS) and may potentially influence platelet function. HYPOTHESIS: We explored the influence of renal function on platelet reactivity to investigate whether high residual platelet reactivity (HRPR) is associated with cardiovascular events. METHODS: ACS patients treated with aspirin and clopidogrel were prospectively enrolled. Patients were categorized into two groups on the basis of baseline estimated glomerular filtration rate (eGFR): non-CKD (eGFR ≥60 mL/min/1.73 m2 ) and CKD (eGFR <60 mL/min/1.73 m2 ). Platelet function was measured by thromboelastography ≥5 days after maintenance dual antiplatelet therapy. Major adverse clinical events (MACEs) were collected at 1 year after discharge. RESULTS: There were 282 non-CKD patients and 212 CKD patients. A significant difference in median MAADP value was observed between the two groups (15.0 mm vs. 31.3 mm, p < .001). HRPR was more prevalent in the CKD group than the non-CKD group (27.4% vs 9.6%, p < .001). At 1-year follow-up, the incidence of MACEs was significantly higher for those with both CKD and HRPR compared with those with either CKD or HRPR (37.9% vs. 18.5%, p < .001). The relationship between HRPR and MACEs was consistent across CKD strata without evidence of interaction. Adding platelet reactivity to eGFR improved the model with area under the curve increasing from 0.703 to 0.734. CONCLUSION: In patients with ACS, the risk of HRPR increased with declining eGFR. Both CKD and HRPR were associated with MACEs at 1-year follow-up.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas , Clopidogrel , Humanos , Rim/fisiologia , Agregação Plaquetária , Inibidores da Agregação Plaquetária/efeitos adversos , Ticagrelor , Ticlopidina/efeitos adversos
12.
Clin Cardiol ; 44(6): 839-847, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33982795

RESUMO

BACKGROUND: After myocardial infarction, guidelines recommend higher-potency P2Y12 receptor inhibitors, namely ticagrelor and prasugrel, over clopidogrel. HYPOTHESIS: We aimed to determine the contemporary use of higher-potency antiplatelet therapy in Canadian patients with non-ST-elevation myocardial infarction (NSTEMI). METHODS: A total of 684 moderate-to-high risk NSTEMI patients were enrolled in the prospective Canadian ACS Reflective II registry at 12 Canadian hospitals and three clinics in five provinces between July 2016 and May 2018. Multivariable logistic regression modeling was performed to assess factors independently associated with higher-potency P2Y12 receptor inhibitor use at discharge. RESULTS: At hospital discharge, 78.3% of patients were treated with a P2Y12 receptor inhibitor. Among patients discharged on a P2Y12 receptor inhibitor, use of higher-potency P2Y12 receptor inhibitor was 61.4%. After adjustment, treatment in-hospital with PCI (OR 4.48, 95%CI 3.34-6.03, p < .0001) was most strongly associated with higher use of higher-potency P2Y12 receptor inhibitor, while oral anticoagulant use at discharge (OR 0.03, 95%CI 0.01-0.12, p < .0001), and atrial fibrillation (OR 0.40, 95%CI 0.17-0.98, p = .046) were most strongly associated with lower use of higher-potency P2Y12 receptor inhibitor. Use of higher-potency P2Y12 receptor inhibitor varied across provinces (range, 21.6%-78.9%). DISCUSSION: In contemporary Canadian practice, approximately 60% of moderate-to-high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor are treated with a higher-potency P2Y12 receptor inhibitor. In addition to factors that increase risk of bleeding, interprovincial differences in practice patterns were associated with use of higher-potency P2Y12 receptor inhibitor at discharge. Opportunities remain for further optimization of evidence-based, guideline-recommended antiplatelet therapy use.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Canadá , Estudos Transversais , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticlopidina , Resultado do Tratamento
14.
Adv Clin Exp Med ; 30(5): 485-489, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33974752

RESUMO

BACKGROUND: Ticagrelor and prasugrel are widely used as antiplatelet therapy after coronary angioplasty. However, there is a group of patients with indications for clopidogrel treatment. This population includes patients with chronic or acute coronary syndrome who are treated invasively and have contraindications to the use of novel antiplatelet drugs due to antithrombotic treatment (particularly with non-vitamin K antagonist oral anticoagulants). A wide range of generic forms of clopidogrel are available on the market. However, it is unclear whether they are as effective as the originator drug. OBJECTIVES: In the current study, we aimed to assess the concentrations of the active metabolite of clopidogrel and its effect on platelet aggregation inhibition in patients receiving the originator drug in comparison with those receiving generic clopidogrel. MATERIAL AND METHODS: We enrolled 22 healthy individuals without polymorphisms in the ABCB1 gene and the allele variants CYPC19*2 and CYPC19*3. All participants received a loading dose of clopidogrel (600 mg), followed by a maintenance dose of 75 mg for the next 3 days. On day 3, blood samples were obtained 1 h after drug administration to assess active metabolite concentrations using liquid chromatography with tandem mass spectrometry. In each participant, platelet aggregation was assessed with light transmission aggregometry after 5-µmol/L and 10-µmol/L adenosine diphosphate (ADP) stimulation. Assays were performed for the originator clopidogrel and 2 different generic groups. RESULTS: The mean ± standard deviation (SD) concentrations of active clopidogrel did not differ between the originator drug and 2 generic products with clopidogrel (12.7±5 pg/µL compared to 13.0 ±4 pg/µL compared to 14.4 ±4 pg/µL). Platelet aggregation inhibition after stimulation with 5 µmol/L and 10 µmol/L ADP was similar for all preparations. CONCLUSIONS: In comparison with original clopidogrel, the use of its generic form does not affect the blood concentrations of the active metabolite or its antiplatelet effect.


Assuntos
Inibidores da Agregação Plaquetária , Ticlopidina , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Alelos , Clopidogrel , Humanos , Agregação Plaquetária
15.
Adv Ther ; 38(6): 3077-3088, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33913121

RESUMO

INTRODUCTION: Both thyroid dysfunction and low responsiveness to clopidogrel have been reported to be associated with increased cardiovascular risk. Our study aims at determining the relationship between free triiodothyronine (FT3) and low responsiveness to clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing elective PCI were enrolled. All patients received a loading dose of 300 mg clopidogrel, and platelet function was assessed by thromboelastography at least 12 h later. Low responsiveness to clopidogrel was defined by an adenosine diphosphate-induced platelet-fibrin clot strength > 47 mm and adenosine diphosphate-induced platelet inhibition rate < 50%. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and ischemia-driven revascularization. RESULTS: Of 812 patients included in the study, 289 showed low responsiveness to clopidogrel. The FT3 level was significantly lower in low responders (4.61 ± 0.60 pmol/l versus 4.94 ± 4.66 pmol/l, p = 0.002). Moreover, the percentage of low responders was greater among patients with low FT3 level than among those without (56.1% versus 34.5%, p = 0.007). Logistic regression analysis showed that a FT3 level was independently associated with the risk of low responsiveness to clopidogrel (odds ratio 0.720, 95% confidence interval [CI] 0.533-0.973, p = 0.033). In patients with low responsiveness to clopidogrel, low FT3 was independently associated with increased risk of MACEs (adjusted hazard ratio 3.040, 95% CI 1.077-8.580, p = 0.036) at a median of 19-month follow-up. CONCLUSIONS: Low FT3 was independently associated with increased risks of both low responsiveness to clopidogrel and cardiovascular events in patients undergoing elective PCI.


Assuntos
Intervenção Coronária Percutânea , Tri-Iodotironina , Clopidogrel , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina , Resultado do Tratamento
16.
J Pak Med Assoc ; 71(2(A)): 540-542, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33819246

RESUMO

Antagonists of the Adenosine Diphosphate (ADP) receptor, P2Y12, may inhibit platelet aggregation as a result of stimulation with arachidonic acid (AA). The potent P2Y12 blocker, Ticagrelor has greater anti-platelet effects than Clopidogrel. We explored the effects of Ticagrelor versus Clopidogrel on mean maximum aggregation ratios (MAR%) in response to AA stimulation in patients receiving aspirin in conventional doses. A total of 613 acute coronary syndrome (ACS) patients were followed from October 2017 to October 2018. At the one- and six-month follow-up visit, mean AA-MAR% was lower in the Ticagrelor group when compared with the Clopidogrel group (28.9% vs 31.7%, 28.4% vs 31.0%, p<0.001 and p=0.001, respectively). BARC1-2 bleeding occurred with greater frequency with Ticagrelor than in patients treated with Clopidogrel (29.3% vs 9.5%, p<0.001; 23.5% vs 9.3%, p<0.001). Excessive platelet inhibition and decreased AA-MAR% were considered the main reasons for the severe subcutaneous/dermal bleeding in Ticagrelor treated patients.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Adenosina/farmacologia , Ácido Araquidônico/farmacologia , Aspirina/farmacologia , Clopidogrel/farmacologia , Clopidogrel/uso terapêutico , Humanos , Agregação Plaquetária , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Ticagrelor , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico , Resultado do Tratamento
17.
Toxicol In Vitro ; 74: 105159, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33823239

RESUMO

Here, we established a high-throughput in vitro assay system to predict reactive metabolite (RM) formation. First, we performed the glutathione (GSH) consumption assay to monitor GSH levels as an index of RM formation potential using HepaRG cells pretreated with 500 µM D,L-buthionine-(S,R)-sulfoximine (BSO) and then treated with ticlopidine and diclofenac. Both drugs, under GSH-reduced conditions, significantly decreased relative cellular GSH content by 70% and 34%, respectively, compared with that in cells not pretreated with BSO. Next, we examined the correlation between GSH consumption and covalent binding assays; the results showed good correlation (correlation coefficient = 0.818). We then optimized the test compound concentration for evaluating RM formation potential using 76 validation compound sets, and the highest sensitivity (53%) was observed at 100 µM. Finally, using HepG2 cells, PXB-cells, and human primary hepatocytes, we examined the cell types suitable for evaluating RM formation potential. The expression of CYP3A4 was highest in HepaRG cells, suggesting the highest sensitivity (56.4%) of the GSH consumption assay. Moreover, a co-culture model of PXB-cells and HepaRG cells showed high sensitivity (72.7%) with sufficient specificity (85.7%). Thus, the GSH consumption assay can be used to effectively evaluate RM formation potential in the early stages of drug discovery.


Assuntos
Ativação Metabólica , Glutationa/metabolismo , Ensaios de Triagem em Larga Escala , Aspirina/toxicidade , Butionina Sulfoximina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Sistema Enzimático do Citocromo P-450/metabolismo , Diclofenaco/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Microssomos Hepáticos/metabolismo , Ticlopidina/toxicidade
19.
Wiad Lek ; 74(2): 228-235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813477

RESUMO

OBJECTIVE: The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well as to study the impact of pantoprazole on the gastric mucosa to optimize the prophylaxis and treatment of gastropathies induced by ASA and clopidogrel. PATIENTS AND METHODS: Materials and methods: The experiments were performed on 77 non-linear white male rats with the average weight of 150-180 g. Depending on the aim of research, the animals were divided into 7 groups. RESULTS: Results: The administration of pantoprazole in combination with ASA and clopidogrel presented positive trends in neutral glycoproteins amount and contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells. CONCLUSION: Conclusions: 1. According to our study findings, administration of ASA in combination with clopidogrel results in 2,5 times higher risk of GM erosive lesions. 2. One of the most significant morphological manifestations of gastropathy in ASA and clopidogrel regimen is the development of microerosions, which are poorly diagnosed by macroscopic examination. 3. The use of PAS-reaction makes possible to identify damage to the basal membrane of superficial epitheliocytes, which may be a top-priority morphological criterion of gastropathy induced by ASA or clopidogrel in the absence of an inflammatory reaction. 4. Administration of pantoprazole in combination with ASA and clopidogrel contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.


Assuntos
Aspirina , Ticlopidina , Animais , Aspirina/efeitos adversos , Clopidogrel , Mucosa Gástrica , Masculino , Pantoprazol , Ratos
20.
Rev Cardiovasc Med ; 22(1): 167-174, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33792258

RESUMO

Our objective was to systematically evaluate the efficacy and safety of proton pump inhibitors combined with clopidogrel in patients undergoing percutaneous coronary intervention and to provide an evidence basis for clinical treatment decision-making. The database EMBASE, PubMed/Medline, Web of Science, the Cochrane Library and CNKI records from establishment of each database until August 2020 were included. Articles were evaluated for quality. Meta-analysis of selected articles was conducted by RevMan5.3 software. Three RCTs and 4 cohort studies were included, with a total of 9932 patients. Four studies reported gastrointestinal (GI) bleeding events, 3 of which were RCT studies. Overall, there was a significantly lower risk of GI bleeding events in the PPI group compared to the no PPI group [OR = 3.06, 95% CI: 1.89 to 4.95] (P < 0.00001). In 3 RCT studies, there was also a significantly lower risk of GI bleeding events in the PPI group compared to the no PPI group [OR = 3.06, 95% CI: 1.80 to 5.21] (P < 0.0001). Seven studies including 3 RCTs and 4 cohort studies reported MACE. Overall, there was no significant difference in MACE events between PPI group and no PPI group [OR = 1.05, 95% CI: 0.91 to 1.21] (P = 0.50). Both in RCT and cohort studies subgroups, there also was no significant difference in MACE events between the PPI group and the no PPI group [OR = 1.16, 95% CI: 0.87 to 1.53] (P = 0.32), [OR = 1.02, 95% CI: 0.87 to 1.19] (P = 0.84), respectively. For PCI patients taking clopidogrel and PPI therapy, PPI reduced the risk of GI bleeding while having no impact on MACE.


Assuntos
Intervenção Coronária Percutânea , Inibidores da Bomba de Prótons , Clopidogrel/efeitos adversos , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Ticlopidina/efeitos adversos , Resultado do Tratamento
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