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1.
Cardiovasc Ther ; 2021: 8836450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33519970

RESUMO

Background: Thrombocytopenia was intuitively considered to be associated with higher risk of bleeding and multiple comorbidities after percutaneous coronary intervention (PCI). However, controversial results exist, and the real-world clinical impact of thrombocytopenia in patients undergoing PCI is largely unknown. The aim of this study was to evaluate the influence of baseline thrombocytopenia on the prognosis of patients undergoing PCI. Methods: Using the West China Hospital Inpatient Sample database, patients who underwent PCI were identified from August 2012 to January 2019. Baseline thrombocytopenia was defined as a preprocedural platelet count of 100 × 109/L or less obtained from a routine blood sample taken within 48 hours before coronary PCI. The clinical effect of the advanced thrombocytopenia group (≤85 × 109/L), according to the median value of platelet count in the thrombocytopenia cohort, was further assessed. The primary outcome was a composite of in-hospital death, bleeding events, and post-PCI transfusion. Results: Of 9531 patients enrolled in our study, 936 had baseline thrombocytopenia and 8595 patients did not have. There were no significant differences in the primary outcome between the two groups. However, advanced thrombocytopenia was independently associated with higher risk of primary outcome (OR 1.67, 95% CI 1.06 to 2.65, p = 0.029). Acute coronary syndrome (ACS) patients with thrombocytopenia were associated with higher odds of major bleeding (BARC ≥ 2) (OR 2.56, 95% CI 1.24 to 5.44, p = 0.011). Compared with the nonthrombocytopenia group, the thrombocytopenia group with ticagrelor use had higher odds of major bleeding (OR 9.7, 95% CI 1.57 to 60.4 versus OR 0.22, 95% CI 0.03 to 1.69, interaction p = 0.025). Conclusions: It seems feasible for patients with thrombocytopenia to receive PCI, but close attention should be paid to advanced thrombocytopenia, the risk of postprocedure bleeding in ACS patients, and the use of more potent P2Y12 inhibitor.


Assuntos
Síndrome Coronariana Aguda/terapia , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea , Trombocitopenia/complicações , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , China , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Feminino , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombocitopenia/diagnóstico , Trombocitopenia/mortalidade , Fatores de Tempo , Resultado do Tratamento
2.
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
3.
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.
Am Heart J ; 227: 82-90, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32693196

RESUMO

BACKGROUND: A number of trials have assessed the efficacy and safety of short-term dual antiplatelet therapy (DAPT) in patients who undergo percutaneous coronary intervention (PCI). However, whether to continue aspirin or a P2Y12 inhibitor after a short course of DAPT is actively debated. METHODS: PUBMED and EMBASE were searched through March 2020 for randomized controlled trials evaluating short-term DAPT (≤6 months) when compared with longer-term (≥12 months) DAPT among patients undergoing PCI. The ischemic outcomes were all-cause death, myocardial infarction, stent thrombosis, and stroke. The safety outcome was major and/or clinically relevant bleeding. The primary objective was to investigate the outcomes with aspirin monotherapy (Aspirin group) versus P2Y12 inhibitor monotherapy (P2Y12i group) after short-term DAPT. RESULTS: Our search identified 17 eligible trials enrolling a total of 54,625 patients comparing different DAPT duration. Either of the 2 monotherapy groups did not increase the risk of ischemic outcomes when compared with the long-term DAPT group, without difference between the Aspirin versus the P2Y12i groups. However, both monotherapy groups significantly reduced bleeding when compared with long-term DAPT (Aspirin group: hazard ratio [95% CI]: 0.62 [0.45-0.86], P=.004 and P2Y12i group: 0.68 [0.50-0.93], P=.015). There was no difference in bleeding between the Aspirin versus P2Y12i groups (hazard ratio=0.91 [0.58-1.43], P=.70). CONCLUSIONS: Among patients undergoing PCI, short-term DAPT with continuation of either aspirin or P2Y12i reduced bleeding without increasing ischemic outcomes when compared with long-term DAPT. The choice of antiplatelet therapy after short-term DAPT should be evaluated in well-powered trials.


Assuntos
Aspirina/administração & dosagem , Terapia Antiplaquetária Dupla/métodos , Metanálise em Rede , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
6.
J Interv Cardiol ; 2020: 5036396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32728350

RESUMO

Objectives: We aimed to identify mechanical and pharmacological revascularization strategies correlated with the index of microcirculatory resistance (IMR) in ST-elevation myocardial infarction (STEMI) patients. Background: Microvascular dysfunction (MVD) after STEMI is correlated with infarct size and poor long-term prognosis, and the IMR is a useful analytical method for the quantitative assessment of MVD. However, therapeutic strategies that can reliably reduce MVD remain uncertain. Methods: Patients with STEMI who underwent primary percutaneous coronary intervention (PCI) were enrolled. The IMR was measured with a pressure sensor/thermistor-tipped guidewire immediately after primary PCI. High IMR was defined as values ≥66th percentile of IMR in enrolled patients (IMR > 30.9 IU). Results: A total of 160 STEMI patients were analyzed (high IMR = 54 patients). Clinical factors for Killip class (P=0.006), delayed hospitalization from symptom onset (P=0.004), peak troponin-I level (P=0.042), and multivessel disease (P=0.003) were associated with high IMR. Achieving final thrombolysis in myocardial infarction myocardial perfusion grade 3 tended to be associated with low IMR (P=0.119), whereas the presence of distal embolization was significantly associated with high IMR (P=0.034). In terms of therapeutic strategies that involved adjusting clinical and angiographic factors associated with IMR, preloading of third-generation P2Y12 inhibitors correlated with reducing IMR value (ß = -10.30, P < 0.001). Mechanical therapeutic strategies including stent diameter/length, preballoon dilatation, direct stenting, and thrombectomy were not associated with low IMR value (all P > 0.05), and postballoon dilatation was associated with high IMR (ß = 8.30, P=0.020). Conclusions: In our study, mechanical strategies were suboptimal in achieving myocardial salvage. Preloading of third-generation P2Y12 inhibitors revealed decreased IMR value, indicative of MVD prevention.


Assuntos
Microcirculação/efeitos dos fármacos , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST , Stents/classificação , Angiografia Coronária/métodos , Circulação Coronária/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Prevenção Secundária/métodos , Trombectomia/métodos , Resistência Vascular/efeitos dos fármacos
7.
Clin Drug Investig ; 40(9): 799-808, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32661914

RESUMO

BACKGROUND AND OBJECTIVES: Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) reduces the incidence of thrombotic events but increases the risk of bleeding, which is associated with a substantial and durable risk of death and could offset the benefits of a reduction in thrombotic events. P2Y12 inhibitor monotherapy after short-term DAPT could be an option to reduce the risk of bleeding. We carried out a meta-analysis comparing P2Y12 inhibitor monotherapy after short-term DAPT with standard-term DAPT in patients undergoing PCI. METHODS: We searched the PubMed and EMBASE databases through 11 April 2020. Two authors independently reviewed and selected eligible trials. The DerSimonian-Laird method with the binary random-effects model was used to calculate the relative risk (RR) with 95% confidence interval (CI). RESULTS: Five trials involving 23,762 patients were included in the final analyses; four were open-label trials, while the TWILIGHT trial was double-blinded. Ticagrelor was used in three trials, and the other two trials included several P2Y12 inhibitors. P2Y12 inhibitor monotherapy after short-term DAPT significantly reduced the bleeding events, defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding, by 39% (RR 0.61, 95% CI 0.38-0.99; p = 0.045) and 46% (RR 0.56, 95% CI 0.42-0.73; p < 0.001), respectively. A significant reduction in cardiovascular death was associated with P2Y12 inhibitor monotherapy after short-term DAPT (RR 0.75, 95% CI 0.58-0.98; p = 0.037; I2 = 0). No significant difference in all-cause mortality, myocardial infarction, stroke, or definite or probable stent thrombosis was observed. CONCLUSIONS: This meta-analysis showed a significantly lowered risk of major bleeding and similar benefits of P2Y12 inhibitor monotherapy after short-term DAPT compared with standard-term DAPT in patients undergoing PCI.


Assuntos
Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem
8.
Circ Cardiovasc Interv ; 13(6): e008649, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32527192

RESUMO

BACKGROUND: Even among biomarker-negative patients undergoing elective percutaneous coronary intervention (PCI), periprocedural thrombotic and bleeding complications can lead to increased morbidity and mortality. Whether stronger platelet inhibition by an intensified oral loading strategy (ILS) before PCI impacts on outcomes among these patients in contemporary practice remains unclear. METHODS: This multicenter, randomized, assessor-blinded trial tested the hypothesis that in elective PCI prasugrel 60 mg (ILS) is superior to standard loading strategy with clopidogrel 600 mg regarding a composite primary end point of all-cause death, any myocardial infarction, definite/probable stent thrombosis, stroke, or urgent vessel revascularization. After PCI, all patients were on clopidogrel 75 mg/day and aspirin. The trial was terminated prematurely because of slower-than-expected recruitment and funding discontinuation. RESULTS: Of 781 patients included in the final analysis, 382 were assigned to ILS and 399 to standard loading strategy. At 30 days, the primary end point occurred in 66 patients (17.3%) assigned to ILS and 74 patients (18.6%) assigned to standard loading strategy (odds ratio, 0.92 [95% CI, 0.63-1.32]; P=0.64). Any myocardial infarction and Bleeding Academic Research Consortium ≥2 bleeding rates were similar among ILS and standard loading strategy groups 16.2% versus 17.5%, odds ratio, 0.91 (95% CI, 0.62-1.32), P=0.62 and 4.2% versus 4.8%, odds ratio 0.87 (95% CI, 0.44-1.73), P=0.70, respectively. CONCLUSIONS: In biomarker-negative stable and unstable angina patients undergoing elective PCI, the trial did not find a conclusive difference in efficacy or safety. This observation should be interpreted in the context of wide CIs and premature termination of the trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02548611.


Assuntos
Clopidogrel/administração & dosagem , Trombose Coronária/prevenção & controle , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Esquema de Medicação , Término Precoce de Ensaios Clínicos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Recidiva , Medição de Risco , Fatores de Risco , Stents , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo , Resultado do Tratamento
10.
J Cardiovasc Pharmacol ; 75(2): 174-179, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32023226

RESUMO

Clopidogrel is still widely used in acute coronary syndrome despite the development of more potent P2Y12 inhibitors. Previously, we conducted a trial that evaluated serial clopidogrel dose adjustment based on platelet function testing in acute coronary syndrome patients with initial high on-treatment platelet reactivity (HTPR). In this substudy, we performed post hoc analysis of the effect of ABCB1 genetic variants C3435T and G2677T/A on platelet inhibition and outcomes. There were no differences in the proportion of HTPR patients among C3435T carriers and noncarriers in both interventional and control group. G2677T carriers expressed significantly higher proportion of HTPR pattern throughout 12-month follow-up in the control group with no difference in the interventional group. There was no difference in ischemic outcomes between C3435T and G2677T carriers and noncarriers in both groups of patients. The results indicate that ABCB1 genotyping is not useful to guide clopidogrel therapy tailoring to improve high-risk patient management.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Clopidogrel/administração & dosagem , Absorção Gastrointestinal/genética , Variantes Farmacogenômicos , Inibidores da Agregação de Plaquetas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Idoso , Plaquetas/metabolismo , Clopidogrel/metabolismo , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/metabolismo , Antagonistas do Receptor Purinérgico P2Y/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Purinérgicos P2Y12/sangue , Resultado do Tratamento
12.
Expert Rev Cardiovasc Ther ; 18(1): 17-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32003297

RESUMO

Introduction: Platelets play a pivotal role in the occurrence of recurrent ischemic events in coronary artery disease patients who are treated with drug-eluting stents and are on dual antiplatelet therapy (DAPT).Areas covered: High platelet reactivity (HPR) to adenosine diphosphate during clopidogrel therapy is a strong predictor of post-stenting ischemic event occurrences. However, uniform use of potent P2Y12 receptors blockers to overcome HPR is associated with elevated bleeding risk. Selective de-escalation of P2Y12 receptor blocker therapy based on PFT in patients with acute coronary syndrome treated with stenting has been shown to be associated with a similar risk of ischemic event occurrence but with a reduced risk of bleeding. This review aims to discuss the role of PFT in guiding DAPT in patients treated with DES. We searched electronic databases from January 2000 to December 2019 for literatures evaluating the role of platelet function assessment after drug eluting stents.Expert opinion: Platelet function guided therapy improves patient outcomes by lessening bleeding and limiting the overuse of highly potent P2Y12 inhibitors. Interest in this area of de-escalation of therapy will likely grow as the consequences of bleeding are better recognized and the cost of healthcare gains greater focus.


Assuntos
Plaquetas/metabolismo , Stents Farmacológicos , Inibidores da Agregação de Plaquetas/administração & dosagem , Síndrome Coronariana Aguda/terapia , Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Quimioterapia Combinada , Stents Farmacológicos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Testes de Função Plaquetária , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem
13.
Cardiovasc Drugs Ther ; 34(2): 199-208, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32006144

RESUMO

PURPOSE: Although current guidelines recommend ticagrelor in addition to aspirin as the antiplatelet strategy for medically managed acute coronary syndrome (MMACS) patients, clinical evidence specific to this special population is lacking. Whether potent oral P2Y12 inhibitors should be used in MMACS patients is still under debate. METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane Library to identify studies exploring the efficacy or safety of ticagrelor and prasugrel versus clopidogrel or placebo in MMACS patients. The primary efficacy endpoint was major adverse cardiovascular events (MACE) defined by each study, and the safety endpoint was TIMI non-CABG major bleeding. RESULTS: A total of 6102 records were screened, and 4 studies including 46,346 patients were finally included. The use of potent oral P2Y12 inhibitors significantly lowers the risk of MACE compared with clopidogrel (HR: 0.90; 95% CI: 0.82-0.98; P = .018; I2 = 0%). A significant reduction in risks of all-cause death and myocardial infarction was also observed with the use of potent oral P2Y12 inhibitors compared with clopidogrel. No significant difference in risks of stroke or TIMI non-CABG major bleeding (HR: 1.24; 95% CI: 0.90-1.73; P = .191; I2 = 0%) was observed between potent oral P2Y12 inhibitors and clopidogrel. CONCLUSION: Potent oral P2Y12 inhibitors, especially ticagrelor, decrease the risk of ischemic events in MMACS patients as compared with clopidogrel, without significantly increasing major bleeding.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/administração & dosagem , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Administração Oral , Idoso , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
EuroIntervention ; 16(2): e164-e172, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32091400

RESUMO

AIMS: We aimed to determine whether shortening the duration of P2Y12 inhibitor therapy can reduce the risk of bleeding without increasing the risk of major adverse cardiovascular events following coronary stenting in patients with atrial fibrillation (AF). METHODS AND RESULTS: The SAFE-A is a randomised controlled trial that compared one-month and six-month P2Y12 inhibitor therapy, in combination with aspirin and apixaban for patients with AF who require coronary stenting. The primary endpoint was the incidence of any bleeding events, defined as Thrombolysis In Myocardial Infarction major/minor bleeding, bleeding with various Bleeding Academic Research Consortium grades, or bleeding requiring blood transfusion within 12 months after stenting. The study aimed to enrol 600 patients but enrolment was slow. Enrolment was terminated prematurely after enrolling 210 patients (72.7±8.2 years; 81% male). The incidence of the primary endpoint did not differ between the one-month and six-month groups (11.8% vs 16.0%; hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.33-1.47; p=0.35). CONCLUSIONS: The study evaluated the safety of withdrawing the P2Y12 inhibitor from triple antithrombotic prescription one month after coronary stenting. However, enrolment was prematurely terminated because it was slow. Therefore, statistical power was not sufficient to assess the differences in the primary endpoint.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/terapia , Stents Farmacológicos/efeitos adversos , Fibrinolíticos/uso terapêutico , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Quimioterapia Combinada , Feminino , Fibrinolíticos/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Inibidores da Agregação de Plaquetas/administração & dosagem , Resultado do Tratamento
15.
Ann Thorac Surg ; 110(1): 13-19, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32057813

RESUMO

BACKGROUND: Continuation of dual antiplatelet therapy (DAPT) after coronary artery bypass grafting (CABG) after acute myocardial infarction is recommended by current guidelines. We sought to evaluate guideline adherence over time and factors associated with postoperative DAPT within a regional consortium. METHODS: Isolated CABG patients from 2011 to 2017 who had a myocardial infarction within 21 days prior to surgery were included. Patients were stratified by DAPT prescription at discharge and by time period, early (2011-2014) vs late (2015-2017). Hierarchical regressions were then performed to evaluate factors influencing DAPT use after CABG. RESULTS: A total of 7314 patients were included with an overall rate of DAPT utilization of 31.2% that increased from 29.6% in the early to 33.4% in the late era (P < .01). There was considerable variability in hospital rates of DAPT (range 9.5%-92.1%) and hospital level changes over time (26% increased, 11% decreased, and 63% remained stable). After adjustment for clinical factors, era was not associated with DAPT use but treating hospital remained significantly associated with DAPT use. Other clinical factors associated with increased DAPT utilization included off-pump surgery (odds ratio [OR] 4.48, P < .01) and prior percutaneous coronary intervention (OR 2.02, P < .01), and atrial fibrillation (OR 0.39, P < .01) was associated with decreased utilization. CONCLUSIONS: Dual antiplatelet use has increased between 2011 and 2017, driven primarily by evolving patient demographics. Significant hospital-level variability drives inconsistency in DAPT utilization. Efforts to promote DAPT use for patients treated with CABG after myocardial infarction in concordance with current guidelines should be targeted at the hospital level.


Assuntos
Aspirina/uso terapêutico , Ponte de Artéria Coronária , Infarto do Miocárdio/cirurgia , Política Organizacional , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Idoso , Aspirina/administração & dosagem , Comorbidade , Ponte de Artéria Coronária/estatística & dados numéricos , Ponte de Artéria Coronária sem Circulação Extracorpórea/estatística & dados numéricos , Quimioterapia Combinada , Feminino , Fidelidade a Diretrizes , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Estudos Retrospectivos , Trombose/prevenção & controle , Virginia/epidemiologia
16.
J Cardiovasc Med (Hagerstown) ; 21(4): 281-285, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32108125

RESUMO

: The European Society of Cardiology guidelines for myocardial revascularization state that de-escalation of P2Y12 inhibitor treatment guided by platelet function testing may be considered for acute coronary syndrome (ACS) patients deemed unsuitable for 12-month potent platelet inhibition. De-escalation strategy aim is to harmonize the time-dependency of thrombotic risk, which is high in the first month after ACS, then decreases exponentially, with bleeding risk, which tends to remain more stable after the procedure-related peak. Harmonizing time-dependency of clinical events may be particularly relevant in those at high risk, such as the elderly patients with ACS in whom an individualized antiplatelet therapy may be more appropriate than a 'one-size-fits all' approach. In this review, we outline the current medical evidence on the topic of dual antiplatelet therapy de-escalation. In addition, we include insights from the Elderly ACS 2 study and recently published post-hoc analyses conducted by the authors' consortium, which further expands current knowledge.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Trombose/prevenção & controle , Síndrome Coronariana Aguda/diagnóstico por imagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Terapia Antiplaquetária Dupla/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
Xenobiotica ; 50(4): 427-434, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31322041

RESUMO

The P2Y12 receptor antagonist selatogrel which exhibits rapid inhibition of platelet aggregation following subcutaneous administration is in development for the treatment of acute myocardial infarction.This human ADME study was performed in six healthy male subjects to determine the routes of elimination and to identify/quantify the metabolites of selatogrel at a therapeutically relevant dose of 16 mg [14C]-radiolabelled selatogrel.The median tmax and t1/2 of selatogrel was 0.75 h and 4.7 h, respectively. It was safe and well tolerated based on adverse event, ECG, vital sign and laboratory data.Geometric mean total recovery of [14C]-radioactivity was 94.9% of which 92.5% was recovered in faeces and 2.4% in urine.Selatogrel was the most abundant entity in each matrix. In plasma, no major metabolite was identified. In excreta, the glucuronide M21 (14.7% of radioactivity) and the mono-oxidized A1 (6.2%) were the most abundant metabolites in urine and faeces, respectively.Overall, none of the metabolic pathways contributed to a relevant extent to the overall elimination of selatogrel, i.e. by more than 25% as defined per regulatory guidance. Hence, no pharmacokinetic interaction studies with inhibitors or inducers of drug-metabolizing enzymes are warranted for clinical development of selatogrel.


Assuntos
Organofosfonatos/farmacocinética , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Pirimidinas/farmacocinética , Administração Cutânea , Adulto , Humanos , Masculino , Taxa de Depuração Metabólica , Organofosfonatos/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Pirimidinas/administração & dosagem
18.
Heart Vessels ; 35(3): 312-322, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31549178

RESUMO

Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y12 inhibitors on platelet reactivity (P2Y12 reaction units: PRU), from acute to late phase after PCI. However, the effect of switching at very late phase is unknown. This study examined the effect on PRU in Japanese coronary heart disease patients with long-term DAPT (aspirin + clopidogrel) when switching from clopidogrel to prasugrel. Ninety-six patients were enrolled in this study. The median DAPT duration at enrollment was 1824.0 days. Twenty-three patients with PRU ≥ 208 at enrollment were randomly assigned into either continuing to receive clopidogrel (Continued Group; n = 11) or switching to prasugrel (Switched Group; n = 12). The primary endpoint was the rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment, which was significantly higher in Switched Group relative to Continued Group (90.0% vs. 36.4%; P = 0.024). The secondary endpoint was the PRU at week 12 in groups subdivided according to cytochrome P450 (CYP) 2C19 genotypes. At week 12, extensive metabolizers (EM Group) had 202.3 ± 60.0 and 174.5 ± 22.3 in Continued Group and Switched Group (P = 0.591), respectively; intermediate and poor metabolizers (non-EM Group) had 229.4 ± 36.9 and 148.4 ± 48.4 in Continued Group and Switched Group (P = 0.002), respectively. The PRU for non-EM Group was significantly reduced in Switched Group. Thus, for patients with long-term DAPT (aspirin + clopidogrel) after PCI with coronary stent implantation, switching from clopidogrel to prasugrel resulted in a stable reduction in PRU, regardless of CYP2C19 polymorphism.


Assuntos
Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Citocromo P-450 CYP2C19/genética , Substituição de Medicamentos , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Variantes Farmacogenômicos , Inibidores da Agregação de Plaquetas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Clopidogrel/efeitos adversos , Clopidogrel/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Citocromo P-450 CYP2C19/metabolismo , Resistência a Medicamentos/genética , Substituição de Medicamentos/efeitos adversos , Terapia Antiplaquetária Dupla , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Agregação Plaquetária/genética , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/metabolismo , Cloridrato de Prasugrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/metabolismo , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
J Cardiovasc Pharmacol Ther ; 25(2): 158-163, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31550912

RESUMO

BACKGROUND: Critical limb-threatening ischemia (CLTI) is associated with an increased risk of major adverse limb events and mortality. High on-treatment platelet reactivity (HPR) is associated with an increased risk of ischemic events, while low on-treatment platelet reactivity (LPR) is associated with an increased risk of bleeding. This study investigates the frequency with which patients with CLTI on clopidogrel or ticagrelor achieve a "therapeutic window" (TW) of platelet inhibition. METHODS: Data from the "Switch To Ticagrelor in Critical Limb Ischemia Anti-Platelet Study" were assessed retrospectively to determine the incidence of TW of on-treatment platelet reactivity in 50 consecutive patients with CLTI (mean age: 65.2 ± 10.5 years, 54% male). The data included 4 measurements of patients' platelet reactivity using the VerifyNow P2Y12 Assay: baseline and steady state platelet reactivity on clopidogrel 75 mg daily and on ticagrelor 90 mg twice daily. RESULTS: At baseline, 46% of patients on clopidogrel were within TW of on-treatment platelet reactivity compared to 10% of patients on ticagrelor (P < .0001). At steady state, 42% of patients on clopidogrel were within the TW compared to 10% of patients on ticagrelor (P < .0001). Patients on ticagrelor exhibited higher rates of LPR compared to those on clopidogrel at baseline as well as at steady state (baseline 88% vs 18%, steady state 88% vs 28%; P < .0001). CONCLUSION: Although ticagrelor has been proposed as an alternative for patients with HPR on clopidogrel, the current study observes an excess of platelet inhibition with ticagrelor in most patients with CLTI at a dose of 90 mg twice daily.


Assuntos
Clopidogrel/administração & dosagem , Isquemia/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem , Idoso , Clopidogrel/efeitos adversos , Estado Terminal , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
Platelets ; 31(1): 26-32, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30585111

RESUMO

Activated platelets contribute to thrombosis and inflammation by the release of extracellular vesicles (EVs) exposing P-selectin, phosphatidylserine (PS) and fibrinogen. P2Y12 receptor antagonists are routinely administered to inhibit platelet activation in patients after acute myocardial infarction (AMI), being a combined antithrombotic and anti-inflammatory therapy. The more potent P2Y12 antagonist ticagrelor improves cardiovascular outcome in patients after AMI compared to the less potent clopidogrel, suggesting that greater inhibition of platelet aggregation is associated with better prognosis. The effect of ticagrelor and clopidogrel on the release of EVs from platelets and other P2Y12-exposing cells is unknown. This study compares the effects of ticagrelor and clopidogrel on (1) the concentrations of EVs from activated platelets (primary end point), (2) the concentrations of EVs exposing fibrinogen, exposing PS, from leukocytes and from endothelial cells (secondary end points) and (3) the procoagulant activity of plasma EVs (tertiary end points) in 60 consecutive AMI patients. After the percutaneous coronary intervention, patients will be randomized to antiplatelet therapy with ticagrelor (study group) or clopidogrel (control group). Blood will be collected from patients at randomization, 48 hours after randomization and 6 months following the index hospitalization. In addition, 30 age- and gender-matched healthy volunteers will be enrolled in the study to investigate the physiological concentrations and procoagulant activity of EVs using recently standardized protocols and EV-dedicated flow cytometry. Concentrations of EVs will be determined by flow cytometry. Procoagulant activity of EVs will be determined by fibrin generation test. The compliance and response to antiplatelet therapy will be assessed by impedance aggregometry. We expect that plasma from patients treated with ticagrelor (1) contains lower concentrations of EVs from activated platelets, exposing fibrinogen, exposing PS, from leukocytes and from endothelial cells and (2) has lower procoagulant activity, when compared to patients treated with clopidogrel. Antiplatelet therapy effect on EVs may identify a new mechanism of action of ticagrelor, as well as create a basis for future studies to investigate whether lower EV concentrations are associated with improved clinical outcomes in patients treated with P2Y12 antagonists.


Assuntos
Protocolos Clínicos , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/metabolismo , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo , Inibidores da Agregação de Plaquetas/administração & dosagem , Trombose/etiologia , Trombose/prevenção & controle , Biomarcadores , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Feminino , Humanos , Masculino , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Ativação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem
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