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1.
J Hosp Infect ; 145: 129-139, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38145812

RESUMO

BACKGROUND: Heart failure (HF) patients are at a greater risk for nosocomial infections due to their higher prevalence of comorbidities, readmission rates, and prolonged hospital stays. Clostridioides difficile infection (CDI) remains a common nosocomial infection in hospitalized patients. AIM: To identify patients with a diagnosis of acute HF and stratified based on the presence of CDI, using the National Inpatient Sample (NIS) database from 2016 to 2020. METHODS: Adjusted odds ratios (aOR) of in-hospital outcomes were calculated, and a propensity-matched analysis was performed. FINDINGS: Of 536,595 acute HF hospitalizations in this timeframe, 3030 were also diagnosed with CDI (0.56%). Patients with acute HF and CDI had significantly higher in-hospital mortality (adjusted odds ratio: (aOR): 1.91), cardiac arrest (aOR: 1.66), and use of mechanical circulatory support (MCS) (aOR 2.42). In propensity-matched analysis, in-hospital mortality (13.71 vs 8.44%; P=0.005), septic shock (7.54 vs 3.33%; P=0.002), and use of MCS (7.19 vs 3.68%; P=0.009) were significantly higher in HF patients with CDI than without. Coexisting neurological disease (aOR: 3.74) and liver disease (aOR: 2.97) showed the strongest association as independent predictors of mortality. HF patients with CDI had longer hospital stays (14.45 ± 19.40 vs 5.44 ± 7.10 days; P<0.0001) and higher inflation-adjusted total hospital costs ($186,225 ± 376,485 vs $60,740 ± 153,992; P<0.001) compared to those without CDI. CONCLUSION: The occurrence of concomitant CDI in patients admitted with acute HF exacerbation is associated with worse in-hospital outcomes and deaths as well as longer hospitalizations and greater financial cost.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Insuficiência Cardíaca , Humanos , Pacientes Internados , Hospitalização , Infecções por Clostridium/diagnóstico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Estudos Retrospectivos
2.
Thromb Haemost ; 112(6): 1198-208, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25182660

RESUMO

Adjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: -2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.


Assuntos
Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Dipiridamol/uso terapêutico , Resistência a Medicamentos , Intervenção Coronária Percutânea , Inibidores da Fosfodiesterase 5/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Aspirina/efeitos adversos , Biomarcadores/sangue , Plaquetas/metabolismo , Moléculas de Adesão Celular/sangue , Clopidogrel , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP3A/genética , Dipiridamol/efeitos adversos , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Proteínas dos Microfilamentos/sangue , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Fosfodiesterase 5/efeitos adversos , Fosfoproteínas/sangue , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Estudos Prospectivos , República da Coreia , Stents , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
3.
Thromb Haemost ; 112(3): 589-97, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25008027

RESUMO

CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC[0-tlast]), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator-stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers/*17 non-carriers). AUC(0-tlast) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [CI]: 0.86,1.17, p>0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p<0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VN-PRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p<0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p<0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p<0.001), and comparable effects in EMs (all p≥0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Citocromo P-450 CYP2C19/genética , Piperazinas/farmacocinética , Inibidores da Agregação Plaquetária/farmacocinética , Tiofenos/farmacocinética , Ticlopidina/análogos & derivados , Idoso , Protocolos Clínicos , Clopidogrel , Doença da Artéria Coronariana/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Piperazinas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/genética , Inibidores da Agregação Plaquetária/administração & dosagem , Polimorfismo Genético , Cloridrato de Prasugrel , Tiofenos/administração & dosagem , Ticlopidina/administração & dosagem , Ticlopidina/farmacocinética , Resultado do Tratamento
4.
Thromb Haemost ; 112(2): 323-31, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24763965

RESUMO

Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB2 was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5-10 mg, 20-40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB2 (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB2 [OR=2.95 (0.1.57-5.50, p=0.0007); OR=2.25 (1.24-4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB2 may be a useful method to optimise statin dosing in order to reduce thrombotic risk.


Assuntos
Aspirina/administração & dosagem , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mediadores da Inflamação/urina , Inibidores da Agregação Plaquetária/administração & dosagem , Tromboxano B2/análogos & derivados , Idoso , Biomarcadores/urina , Coagulação Sanguínea/efeitos dos fármacos , Distribuição de Qui-Quadrado , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/urina , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Tromboelastografia , Tromboxano B2/urina , Resultado do Tratamento , Ultracentrifugação
6.
Thromb Haemost ; 109(5): 808-16, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23254993

RESUMO

Various diagnostic and prognostic performance measures have been used to describe the clinical usefulness of platelet function testing in the evaluation and management of patients taking P2Y12 inhibitors, which reduce the risk for thrombosis due to their action on the platelet P2Y12 receptor. Platelet function tests are used to confirm the presence of an antiplatelet effect of a P2Y12 inhibitor, and confirmation that the pharmacodynamic effect is associated with a reduction in the rate of thrombosis. Despite this clear association, enthusiasm for the clinical usefulness of platelet function testing has been tempered based on observed sensitivity, specificity, and positive predictive value for the detection of future thrombotic events. However, evaluating the prognostic utility of a test based on diagnostic performance indicators is not appropriate because prognostic tests are not used to diagnose which patients will have events; instead, they are used to assist in risk stratification. Therefore, when evaluating the usefulness of platelet function testing, diagnostic performance measures such as sensitivity, specificity, and predictive values should focus on diagnostic performance in identifying a pharmacodynamic effect, and prognostic performance should be evaluated using prognostic performance measures such as hazard ratios and net reclassification improvement, which are comparable to other well-established risk factors for cardiovascular events.


Assuntos
Plaquetas/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Testes de Função Plaquetária , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Plaquetas/metabolismo , Resistência a Medicamentos , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária/métodos , Testes de Função Plaquetária/normas , Valor Preditivo dos Testes , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12/sangue , Medição de Risco , Fatores de Risco , Resultado do Tratamento
8.
Clin Pharmacol Ther ; 90(6): 860-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22048221

RESUMO

PA32540 combines 325 mg enteric-coated (EC) aspirin (ASA) with 40 mg immediate-release omeprazole; its influence on the antiplatelet effect of clopidogrel (C) is unknown. In this randomized, open-label study, subjects (n = 30) were treated with (i) 300 mg C + 325 mg ECASA followed by 75 mg C + 325 mg ECASA on days 2-7, (ii) 300 mg C + PA32540 followed by 75 mg C + PA32540 on days 2-7, or (iii) PA32540 in the morning + 300 mg C 10 h later on day 1 and PA32540 in the morning + 75 mg C 10 h later on days 2-7. We analyzed the noninferiority of PA32540 relative to ECASA, as defined by the upper bound of the 95% confidence interval ≤10% for the difference in least-square means of platelet inhibition between the treatments. As compared to ECASA+C, synchronous treatment of PA32540+C was not noninferior, whereas the spacing strategy of PA32540+C was noninferior. Spacing the administration of PA32540 and clopidogrel lessens the interaction observed with synchronous administration; PA32540 administration with clopidogrel may be associated with a different antiplatelet profile.


Assuntos
Aspirina/farmacologia , Omeprazol/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Ticlopidina/análogos & derivados , Adulto , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Aspirina/administração & dosagem , Clopidogrel , Estudos Cross-Over , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Interações Medicamentosas , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Omeprazol/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Comprimidos com Revestimento Entérico , Ticlopidina/administração & dosagem , Ticlopidina/farmacologia
9.
Clin Pharmacol Ther ; 90(4): 568-74, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21881565

RESUMO

A common functional variant in paraoxonase 1 (PON1), Q192R, was recently reported to be a major determinant of clopidogrel response. This variant was genotyped in 566 participants of the Amish Pharmacogenomics of Anti-Platelet Intervention (PAPI) study and in 227 percutaneous coronary intervention (PCI) patients. Serum paraoxonase activity was measured in a subset of 79 PAPI participants. PON1 Q192R was not associated with pre- or post-clopidogrel platelet aggregation in the PAPI study (P = 0.16 and P = 0.21, respectively) or the PCI cohort (P = 0.47 and P = 0.91, respectively). The Q192 allele was not associated with cardiovascular events (hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.20-1.06; P = 0.07). No correlation was observed between paraoxonase activity and post-clopidogrel platelet aggregation (r(2) < 0.01, P = 0.78). None of 49 additional PON1 variants evaluated was associated with post-clopidogrel platelet aggregation. These findings do not support a role for PON1 as a determinant of clopidogrel response.


Assuntos
Arildialquilfosfatase/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/mortalidade , Estudos de Associação Genética/métodos , Variação Genética/genética , Ticlopidina/análogos & derivados , Adulto , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Clopidogrel , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Ticlopidina/uso terapêutico , Resultado do Tratamento
10.
J Thromb Haemost ; 9(10): 1902-15, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21777368

RESUMO

BACKGROUND: The aim of the current study was to perform two separate meta-analyses of available studies comparing low-molecular-weight heparins (LMWHs) vs. unfractionated heparin (UFH) in ST-elevation myocardial infarction (STEMI) patients treated (i) with primary percutaneous coronary intervention (pPCI) or (ii) with PCI after thrombolysis. METHODS: All-cause mortality was the pre-specified primary endpoint and major bleeding complications were recorded as the secondary endpoints. Relative risk (RR) with a 95% confidence interval (CI) and absolute risk reduction (ARR) were chosen as the effect measure. RESULTS: Ten studies comprising 16,286 patients were included. The median follow-up was 2 months for the primary endpoint. Among LMWHs, enoxaparin was the compound most frequently used. In the pPCI group, LMWHs were associated with a reduction in mortality [RR (95% CI) = 0.51 (0.41-0.64), P < 0.001, ARR = 3%] and major bleeding [RR (95% CI) = 0.68 (0.49-0.94), P = 0.02, ARR = 2.0%] as compared with UFH. Conversely, no clear evidence of benefits with LWMHs was observed in the PCI group after thrombolysis. Meta-regression showed that patients with a higher baseline risk had greater benefits from LMWHs (r = 0.72, P = 0.02). CONCLUSIONS: LMWHs were associated with greater efficacy and safety than UFH in STEMI patients treated with pPCI, with a significant relationship between risk profile and clinical benefits. Based on this meta-analysis, LMWHs may be considered as a preferred anticoagulant among STEMI patients undergoing pPCI.


Assuntos
Angioplastia Coronária com Balão , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina/uso terapêutico , Infarto do Miocárdio/cirurgia , Eletrocardiografia , Humanos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia
11.
J Thromb Haemost ; 9(9): 1730-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21707911

RESUMO

BACKGROUND: The rate of recovery of platelet function after discontinuation of P2Y(12) inhibitors depends on the reversibility of the antiplatelet effect and the extent of the on-treatment response. P2Y(12) inhibition increases the bleeding risk in patients requiring surgery. OBJECTIVES: To evaluate recovery of platelet function after discontinuation of ticagrelor vs. clopidogrel in stable coronary artery disease (CAD) patients with high levels of platelet inhibition (HPI) during the ONSET/OFFSET study. METHODS: Patients received aspirin 75-100 mg per day and either ticagrelor 90 mg twice-daily or clopidogrel 75 mg daily for 6 weeks. This subanalysis included patients with HPI after the last dose of maintenance therapy, defined as: inhibition of platelet aggregation (IPA) > 75% 4 h post-dose (ADP 20 µm, final extent); < 120 P2Y(12) reaction units 8 h post-dose (VerifyNow P2Y(12) assay); or platelet reactivity index < 50% 8 h post-dose (VASP-P assay). RESULTS: IPA > 75% was observed in 39 out of 47 ticagrelor-treated and 17 out of 44 clopidogrel-treated patients. The rate of offset of IPA over 4-72 h was greater with ticagrelor (IPA %/hour slope: -1.11 vs. -0.67 for clopidogrel; P < 0.0001). Mean IPA was significantly lower with ticagrelor than clopidogrel between 48 and 168 h post-dose (P < 0.01). Similar findings were observed with the other assays. The average time for IPA to decline from 30% to 10% was 50.8 h with ticagrelor vs. 110.4 h with clopidogrel. CONCLUSIONS: In patients with HPI, recovery of platelet function was more rapid after discontinuation of ticagrelor than clopidogrel leading to significantly greater platelet reactivity by 48 h after the last dose in the ticagrelor group.


Assuntos
Adenosina/análogos & derivados , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticlopidina/análogos & derivados , Adenosina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Ticagrelor , Ticlopidina/administração & dosagem , Fatores de Tempo
12.
J Thromb Haemost ; 8(1): 43-53, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19817997

RESUMO

UNLABELLED: To study the effect of a new direct acting reversible P2Y(12) inhibitor, elinogrel (PRT060128), and the relation to cytochrome P450 (CYP) polymorphisms in patients with high platelet reactivity (HPR) on standard dual antiplatelet therapy. METHODS AND RESULTS: We studied the pharmacodynamic and pharmacokinetic effects of a single 60-mg oral dose of elinogrel in 20 of 45 previously stented stable patients with HPR. We also genotyped for CYP2C19*2,3,5,17 and CYP3A5*3. Platelet reactivity fell within 4 h of dosing, the earliest time point evaluated as measured by the following assays: maximum 5 and 10 microM ADP LTA (P < 0.001 for both vs. predosing); maximum 20 microM ADP LTA (P < 0.05); VerifyNow (P < 0.001); thrombelastography (P < 0.05); VASP phosphorylation (P < 0.01); and perfusion chamber assay (P < 0.05); this was reversible within 24 h in these same assays (P = ns vs. predosing for all assays). CYP2C19*2 was present in 44% of all patients but was more frequent in HPR patients (77% vs. 16%, P = 0.0004). CONCLUSIONS: HPR is reversibly overcome by a single 60-mg oral dose of elinogrel, a drug now being investigated in a phase 2 trial. CYP2C19*2 was associated with HPR during conventional dual antiplatelet therapy.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Doença da Artéria Coronariana/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo Genético , Antagonistas do Receptor Purinérgico P2 , Quinazolinonas/uso terapêutico , Sulfonamidas/uso terapêutico , Ticlopidina/análogos & derivados , Difosfato de Adenosina , Administração Oral , Idoso , Angioplastia Coronária com Balão/instrumentação , Hidrocarboneto de Aril Hidroxilases/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/metabolismo , Moléculas de Adesão Celular/sangue , Clopidogrel , Colágeno/uso terapêutico , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP3A/genética , Quimioterapia Combinada , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Proteínas dos Microfilamentos/sangue , Pessoa de Meia-Idade , Fenótipo , Fosfoproteínas/sangue , Fosforilação , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacocinética , Quinazolinonas/administração & dosagem , Quinazolinonas/farmacocinética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2Y12 , Stents , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacocinética , Tromboelastografia , Ticlopidina/uso terapêutico
13.
Hamostaseologie ; 29(4): 368-75, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19882080

RESUMO

Percutaneous coronary intervention (PCI) has significantly improved clinical outcomes in coronary artery disease patients. Since PCI is associated with platelet activation, antiplatelet therapy with aspirin, clopidogrel and GPIIb/IIIa inhibitors comprise the cornerstone strategy during and following PCI. The latter agents are arguably the most important drugs we administer to the patient with established coronary artery disease since they are specifically given to prevent the most catastrophic event, the formation of an occlusive arterial thrombus. Numerous clinical trials have confirmed the efficacy of antiplatelet therapy in attenuating recurrent ischaemic event occurrence. Despite the extensive use of antiplatelet therapies, ischaemic event occurrence such as post-procedural myocardial infarction and stent thrombosis still remains an important concern and highlights the need for improved treatment strategies. A major limitation of current treatment is the application of a "one size fits all" strategy advocated by the guidelines that completely ignores the evaluation of the individual antiplatelet response. Pharmacodynamic studies have revealed the limitations of aspirin and clopidogrel treatment that include response variability, and a high prevalence of antiplatelet non-responsiveness associated with significant risk for recurrent ischemic event occurrence. Thus, two major paradoxes in cardiovascular medicine today are: 1) despite the overwhelming evidence that platelet reactivity strongly influences the development of potentially catastrophic events including myocardial infarction and stent thrombosis in the PCI patient, no measurement is made in clinical practice to assess the presence of blood vulnerability (platelet reactivity) and 2) despite the overwhelming evidence that the effect of dual antiplatelet therapy with aspirin and P2Y12 receptor blockers is variable, the guidelines largely recommend a uniform, "one size fits all" dosing of these agents in the PCI patient without any confirmation of an adequate antiplatelet effect.


Assuntos
Plaquetas/fisiologia , Coagulação Sanguínea/fisiologia , Plaquetas/efeitos dos fármacos , Clopidogrel , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Humanos , Monitorização Fisiológica/métodos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Ativação Plaquetária/efeitos dos fármacos , Adesividade Plaquetária , Inibidores da Agregação Plaquetária/uso terapêutico , Medicina de Precisão/métodos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico
15.
Neth Heart J ; 15(4): 148-50, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17612675

RESUMO

Notice of the rare but catastrophic occurrence of stent thrombosis in association with deployment of drug-eluting stents has focused attention on the adequacy of the current dual antiplatelet regimen of aspirin and clopidogrel. Some patients will not respond to clopidogrel and a glycoprotein (GP) IIb/IIIa inhibitor may be strongly considered during stenting procedures, especially in high-risk patients or those not receiving pretreatment with clopidogrel. Insisting upon and confirming adherence to antiplatelet therapy are complicated tasks, especially because the reasons for premature discontinuation are myriad, from cost to bleeding complications to the need for minor surgery. Nevertheless, the concern about adherence to antiplatelet therapy represents a new and significant clinical reality in our stenting era, one previously less appreciated with the deployment of bare metal stents. (Neth Heart J 2007;15:148-50.).

20.
Am Heart J ; 142(4): 611-6, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11579350

RESUMO

BACKGROUND: Platelets play an important role in the natural history of coronary artery disease. Enhanced platelet aggregation and receptor expression unquestionably occur after coronary stent implantation; however, the functional characteristics of platelets before stenting have not been fully elucidated. METHODS: Platelets were assessed before intervention by platelet-rich plasma aggregation (PA) with 5 mmol adenosine diphosphate (ADP) and 1 mg/mL collagen; whole blood aggregation (WBA) by 1 mg/mL collagen; shear-induced closure time (CT); contractile force (CF); and expression of 9 surface receptors by flow cytometry in 126 patients undergoing elective coronary artery stent placement. All patients received aspirin for at least 7 days. The data were compared with those from 64 healthy volunteers. RESULTS: Each test revealed sustained platelet activation in patients undergoing coronary stenting compared with control values. These differences were significant for collagen-induced PA (P =.031); CF (P =.0001); expression of glycoprotein (GP) IIb/IIIa (P =.0001); P-selectin (P =.0008); platelet/endothelial cell adhesion molecule (PECAM)-1 (P =.0001); CD107a (P =.0001); CD107b (P =.0004); and CD63 (P =.009). CONCLUSION: Platelets are indeed activated before coronary stenting despite antecedent therapy with aspirin.


Assuntos
Aspirina/uso terapêutico , Doença das Coronárias/sangue , Doença das Coronárias/cirurgia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Cuidados Pré-Operatórios , Stents , Adulto , Aspirina/farmacologia , Doença das Coronárias/tratamento farmacológico , Vasos Coronários/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia
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