RESUMO
BACKGROUND: Standardisation of referral pathways and the transfer of patients with acute aortic syndromes (AAS) to regional centres are recommended by NHS England in the Acute Aortic Dissection Toolkit. The aim of the Transfer of Thoracic Aortic Vascular Emergencies to Regional Specialist INstitutes Group study was to establish an interdisciplinary consensus on the interhospital transfer of patients with AAS to specialist high-volume aortic centres. METHODS: Consensus on the key aspects of interhospital transfer of patients with AAS was established using the Delphi method, in line with Conducting and Reporting of Delphi Studies guidelines. A national patient charity for aortic dissection was involved in the design of the Delphi study. Vascular and cardiothoracic surgeons, emergency physicians, interventional radiologists, cardiologists, intensivists and anaesthetists in the United Kingdom were invited to participate via their respective professional societies. RESULTS: Three consecutive rounds of an electronic Delphi survey were completed by 212, 101 and 58 respondents, respectively. Using predefined consensus criteria, 60 out of 117 (51%) statements from the survey were included in the consensus statement. The study concluded that patients can be taken directly to a specialist aortic centre if they have typical symptoms of AAS on the background of known aortic disease or previous aortic intervention. Accepted patients should be transferred in a category 2 ambulance (response time <18 min), ideally accompanied by transfer-trained personnel or Adult Critical Care Transfer Services. A clear plan should be agreed in case of a cardiac arrest occurring during the transfer. Patients should reach the aortic centre within 4 hours of the initial referral from their local hospital. CONCLUSIONS: This consensus statement is the first set of national interdisciplinary recommendations on the interhospital transfer of patients with AAS. Its implementation is likely to contribute to safer and more standardised emergency referral pathways to regional high-volume specialist aortic units.
Assuntos
Dissecção Aórtica , Adulto , Humanos , Técnica Delphi , Dissecção Aórtica/terapia , Encaminhamento e Consulta , Reino Unido , InglaterraRESUMO
BACKGROUND: FFRCT assesses the functional significance of lesions seen on CTCA, and may be a more efficient approach to chest pain evaluation. The FORECAST randomized trial found no significant difference in costs within the UK National Health Service, but implications for US costs are unknown. The purpose of this study was to compare costs in the FORECAST trial based on US healthcare cost weights, and to evaluate factors affecting costs. METHODS: Patients with stable chest pain were randomized either to the experimental strategy (CTCA with selective FFRCT), or to standard clinical pathways. Pre-randomization, the treating clinician declared the planned initial test. The primary outcome was nine-month cardiovascular care costs. RESULTS: Planned initial tests were CTCA in 912 patients (65%), stress testing in 393 (28%), and invasive angiography in 94 (7%). Mean US costs did not differ overall between the experimental strategy and standard care (cost difference +7% (+$324), CI -12% to +26%, p â= â0.49). Costs were 4% lower with the experimental strategy in the planned invasive angiography stratum (p for interaction â= â0.66). Baseline factors independently associated with costs were older age (+43%), male sex (+55%), diabetes (+37%), hypertension (+61%), hyperlipidemia (+94%), prior angina (+24%), and planned invasive angiography (+160%). Post-randomization cost drivers were coronary revascularization (+348%), invasive angiography (267%), and number of tests (+35%). CONCLUSIONS: Initial evaluation of chest pain using CTCA with FFRCT had similar US costs as standard care pathways. Costs were increased by baseline coronary risk factors and planned invasive angiography, and post-randomization invasive procedures and the number of tests. Registration at ClinicalTrials.gov (NCT03187639).
Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Humanos , Masculino , Angiografia Coronária/métodos , Medicina Estatal , Valor Preditivo dos Testes , Angina Pectoris/terapia , Angiografia por Tomografia Computadorizada/métodosRESUMO
BACKGROUND: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone. METHODS: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non-ST-segment-elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events. RESULTS: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3-5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613-£7015); and angiography+FFR, £4510 (£2721-£7415; P=0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60-87); and angiography+FFR, 75 (interquartile range, 60-90; P=0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR (P=0.64). CONCLUSIONS: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01070771.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Estenose Coronária/diagnóstico , Humanos , Qualidade de Vida , Medicina Estatal , Resultado do TratamentoRESUMO
We present a case of angina, where extreme coronary tortuosity affected invasive physiology interpretation. Extreme coronary tortuosity may lower fractional flow reserve and instantaneous wave-free ratio. Therefore, invasive physiology can be misleading in this setting, when used to evaluate stenosis significance, or when used post-percutaneous coronary (PCI) intervention for physiology guided stent optimisation.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Cateterismo Cardíaco , Angiografia Coronária , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
OBJECTIVE: Evidence supports improved outcomes and reduced mortality with rapid reperfusion through primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI). UK national audit data (Myocardial Ischaemia National Audit Project [MINAP]) demonstrates minor improvements in door-to-balloon times (DTB) of <90 min but increasing call-to-balloon times (CTB). We evaluate the effect of a regional Cardiologist delivered paramedic education programme (PEP) on DTB times and appropriate use of the PPCI pathway. METHODS: This was a prospective single-centre study of patients with STEMI brought directly to hospital via ambulance services. Data sources included ambulance charts, in-patient notes, British Cardiovascular Interventional Society (BCIS) database and local MINAP data. All DTB breaches were investigated. A local PEP was implemented with focus on ECG interpretation, STEMI diagnosis and appropriate use of the PPCI pathway. Non-parametric Wilcoxon rank test was used for comparisons of DTB and CTB times between direct versus ED-associated cath lab transfer. RESULTS: A total of 728 patients with STEMI were admitted directly to our centre via ambulance, 66% (n=484) directly to the Catheterisation Laboratory (Cath Lab) and 34% (n=244) via the Emergency Department (ED). There was a significant increase in median DTB, 83 vs 37 min (p<0.001) and median CTB 144 vs 97.5 min (p<0.001) when transfer to the Cath Lab occurred via the ED versus direct transfer. The PEP increased direct cath lab transfers (52%-85%) and generated annual reductions in median DTB times, with sustained improvement seen throughout the 7-year study period. CONCLUSIONS: Paramedic education increases direct transfer of STEMI patients to the Cath Lab, and reduces DTB times. This is an effective and reproducible intervention to facilitate timely reperfusion in STEMI.
Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Pessoal Técnico de Saúde , Eletrocardiografia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores de TempoRESUMO
AIMS: Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care. METHODS AND RESULTS: Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months. Secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized groups were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFRCT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from -£112 (-8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01). CONCLUSION: A strategy of CTCA with selective FFRCT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography.
Assuntos
Angina Estável , Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Angina Estável/diagnóstico por imagem , Angina Estável/terapia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários , Humanos , Valor Preditivo dos Testes , Qualidade de VidaRESUMO
OBJECTIVE: To understand human factors (HF) contributing to disturbances during invasive cardiac procedures, including frequency and nature of distractions, and assessment of operator workload. METHODS: Single centre prospective observational evaluation of 194 cardiac procedures in three adult cardiac catheterisation laboratories over 6 weeks. A proforma including frequency, nature, magnitude and level of procedural risk at the time of each distraction/interruption was completed for each case. The primary operator completed a National Aeronautical and Space Administration (NASA) task load questionnaire rating mental/physical effort, level of frustration, time-urgency, and overall effort and performance. RESULTS: 264 distractions occurred in 106 (55%) out of 194 procedures observed; 80% were not relevant to the case being undertaken; 14% were urgent including discussions of potential ST-elevation myocardial infarction requiring emergency angioplasty. In procedures where distractions were observed, frequency per case ranged from 1 to 16 (mean 2.5, SD ±2.2); 43 were documented during high-risk stages of the procedure. Operator rating of NASA task load parameters demonstrated higher levels of mental and physical workload and effort during cases in which distractions occurred. CONCLUSIONS: In this first description of HF in adult cardiac catheter laboratories, we found that fewer than half of all procedures were completed without interruption/distraction. The majority were unnecessary and without relation to the case or list. We propose the introduction of a 'sterile cockpit' environment within catheter laboratories, as adapted from aviation and used in surgical operating theatres, to minimise non-emergent interruptions and disturbances, to improve operator conditions and overall patient safety.
Assuntos
Reabilitação Cardíaca/normas , Cardiologistas/normas , Competência Clínica , Segurança do Paciente/normas , Adulto , Humanos , Masculino , Estudos ProspectivosRESUMO
In contrast to short thrombelastography (s-TEG) which utilises adenosine diphosphate (ADP) alone, the VerifyNow P2Y12 assay (VN-P2Y12) additionally uses prostaglandin E1 (PGE1) as agonist to assess response to P2Y12 inhibitors. Based upon previous observations, we hypothesised that VN-P2Y12 overestimates the therapeutic effects of clopidogrel. Simultaneous assay with s-TEG and VN-P2Y12 was performed in 43 healthy volunteers and 170 patients either on or off clopidogrel. Furthermore, in 27 patients on clopidogrel 75 mg we compared the effects of adding 22 nM PGE1 to ADP on platelet aggregation in s-TEG to ADP alone. A higher proportion of individuals had a result indicating high platelet reactivity (HPR) with s-TEG than VN-P2Y12 in (i) 43 clopidogrel naïve volunteers (95.3% vs 81.4%, p = NS); (ii) 28 volunteers loaded with clopidogrel 600 mg (39.3% vs 10.7 %, p = < 0.01); (iii) 123 clopidogrel naïve patients (93.5% vs 78%, p = < 0.0001); (iv) 47 patients on clopidogrel 75 mg (42.6% vs 4.3%, p = < 0.0001). In 59 patients loaded with clopidogrel 600 mg/900 mg, a greater proportion had a "therapeutic response" with VN-P2Y12 compared to s-TEG, regardless of the threshold for defining HPR with VN-PY12 (P2Y12 reaction units ≥ 230 or 208). Furthermore, adding PGE1 to ADP in s-TEG potentiated the anti-aggregatory effects of clopidogrel compared with ADP alone. In conclusion, VN-P2Y12 overestimates the functional effects of clopidogrel in some individuals, possibly because it utilises PGE1 in addition to ADP. This could have implications for the ability of VN-P2Y12 to stratify patients as "responders" or "non-responders" to clopidogrel.
Assuntos
Testes de Função Plaquetária/métodos , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y12/sangue , Tromboelastografia/métodos , Ticlopidina/análogos & derivados , Difosfato de Adenosina/administração & dosagem , Alprostadil/administração & dosagem , Clopidogrel , Sinergismo Farmacológico , Humanos , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária/estatística & dados numéricos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Tromboelastografia/estatística & dados numéricos , Ticlopidina/administração & dosagem , Ticlopidina/farmacologiaRESUMO
BACKGROUND: The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws. The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined. METHODS AND RESULTS: Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (≥2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA. CONCLUSIONS: Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrial.gov. Unique identifier: NCT01070771.
Assuntos
Dor no Peito/diagnóstico , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Idoso , Dor no Peito/etiologia , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/fisiopatologia , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Resultado do Tratamento , Reino UnidoRESUMO
AIMS: To establish success and complication rates of excimer laser coronary atherectomy (ELCA) in a contemporary series of patients with balloon failure during percutaneous coronary intervention (PCI) of both chronic total occlusions (CTO) and lesions with distal TIMI 3 flow. METHODS AND RESULTS: We identified 58 cases of balloon failure treated with ELCA±rotational atherectomy (RA) over four years, representing 0.84% of all PCI performed in our centre during this period. Balloon failures were classified according to: (i) mechanism of balloon failure; and (ii) whether this occurred in the context of treating a CTO. ELCA was performed following balloon failure using the CVX-300 Excimer Laser System and a 0.9 mm catheter with saline flush. For the entire cohort, procedure success was achieved in 91% (with ELCA successful: alone in 76.1%, after RA failure in 6.8% and in combination with RA for 8.6%). Only in one case did RA succeed where ELCA had failed. There were four procedure-related complications, including transient no-reflow, side branch occlusion and two coronary perforations, of which one was directly attributable to ELCA and led to subsequent mortality. CONCLUSIONS: ELCA provides safe and effective adjunctive therapy in contemporary PCI to treat lesions associated with balloon failure due to an inability either to cross the lesion or to expand a balloon sufficiently to permit stenting. ELCA was successful in the majority of these selected cases when used independently with further effectiveness achieved when combined with RA or after RA failure.
Assuntos
Aterectomia Coronária/instrumentação , Doença da Artéria Coronariana/terapia , Oclusão Coronária/terapia , Lasers de Excimer/uso terapêutico , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Aterectomia Coronária/efeitos adversos , Aterectomia Coronária/métodos , Cateteres Cardíacos , Doença Crônica , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Oclusão Coronária/diagnóstico , Desenho de Equipamento , Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Antiplatelet therapy with aspirin and clopidogrel in PCI patients, though effective, is still associated with thrombotic complications. These are multifactorial in origin, but partially attributable to "clopidogrel resistance." However, how best to identify and manage "clopidogrel resistance" remains unclear. Targeting therapeutic changes specifically at those individuals with poor response to clopidogrel is likely to be a solution. A "one size fits all" approach to clopidogrel dosing is probably flawed. This review will explore (1) the definition and mechanisms of clopidogrel resistance, (2) assessment of clopidogrel resistance by (i) platelet function testing and (ii) genetic testing, (3) the management of "clopidogrel resistance," and (4) newer antiplatelet agents, and evolving stent technology. A pubmed literature review was performed using the keywords "clopidogrel", "resistance", "poor response", "adverse events", "platelet function tests", and "genetic tests". In looking at new agents, keywords "prasugrel", "cangrelor", "ticagrelor""Elinogrel", and "P2Y12 receptor antagonists" were used. Third, a search was performed looking at "stent design", "IVUS", "bioabsorbable stents", and "stent apposition". Whilst new P2Y12 receptor antagonists and improved stent technology may reduce thrombotic events in the future, there is still a need for clopidogrel. There is good evidence that poor response to clopidogrel is associated with adverse outcome. Platelet function tests probably provide more clinically useful data than genetic tests, but the question of how best to identify and manage variability in response to clopidogrel demands further research.
Assuntos
Resistência a Medicamentos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Clopidogrel , Relação Dose-Resposta a Droga , Substituição de Medicamentos , Hemorragia/induzido quimicamente , Humanos , Adesão à Medicação , Farmacogenética , Agregação Plaquetária/genética , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Testes de Função Plaquetária , Valor Preditivo dos Testes , Fatores de Risco , Trombose/sangue , Trombose/genética , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/farmacocinética , Falha de TratamentoRESUMO
BACKGROUND: An 80-year-old man with limiting angina pectoris. INVESTIGATION: Physical examination, laboratory tests, echocardiography, exercise ECG, coronary arteriography, pressure wire assessment. DIAGNOSIS: Single severe calcific coronary artery disease. TREATMENT: Elective percutaneous coronary intervention (PCI) for calcific mid-vessel stenosis with rotational and excimer laser atherectomy.
Assuntos
Angioplastia Coronária com Balão/métodos , Aterectomia Coronária/métodos , Calcinose/terapia , Doença da Artéria Coronariana/terapia , Índice de Gravidade de Doença , Idoso de 80 Anos ou mais , Calcinose/diagnóstico , Calcinose/patologia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Ecocardiografia , Eletrocardiografia , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: A significant proportion of patients receiving dual antiplatelet therapy following percutaneous coronary intervention experience recurrent ischaemic events despite standard doses of treatment. Although clinical studies show significant heterogeneity in antiplatelet therapy responses, routine testing is not undertaken due to (i) lack of a standardized test, and (ii) poor clarity with regards to definition of abnormal responses. Short Thrombelastography (s-TEG) is a validated test that allows rapid measurement of clotting responses to antiplatelet therapy. OBJECTIVES: This study sought to determine the reproducibility of s-TEG and to compare s-TEG with VerifyNow in assessment of responses to antiplatelet therapy. METHODS: (i) intra-individual variability was assessed using s-TEG Area Under the Curve (AUC15) and maximum amplitude (MA) in one volunteer at 20 time-points on no medication and at 10 time-points pre and post 300 mg aspirin treatment (ii) inter-individual variability was determined from a retrospective analysis of data on MA and AUC15 obtained from 56 volunteers on no medication, 25 volunteers pre and post 300 mg aspirin treatment and 28 patients pre and post 600 mg clopidogrel treatment (iii) a comparison between AUC15 arachidonic-acid (AA) channel and VerifyNow aspirin response units (VN ARU) and between AUC15 adenosine diphosphate (ADP) channel and VerifyNow P2Y12 reactivity units (VN PRU) was obtained from retrospective analysis of data at 370 and 296 time-points respectively. RESULTS: There was minimal intra-and inter-individual variability in MA and AUC15 in the AA, ADP and thrombin channels. There was a good correlation between AA AUC15 and VN ARU (r = 0.701, p < 0.001) and between ADP AUC15 and VN PRU (r = 0.609, p < 0.001). CONCLUSIONS: s-TEG is a reproducible and reliable near-patient test that correlates well with VerifyNow. Large scale studies are needed to determine its potential role in individually tailored antiplatelet therapy.
Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Tromboelastografia/métodos , Aspirina/uso terapêutico , Clopidogrel , Humanos , Individualidade , Reprodutibilidade dos Testes , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêuticoRESUMO
Whilst poor response to clopidogrel is associated with adverse outcomes uncertainty exists as to how (a) response should be assessed and (b) poor responders managed. We utilised VerifyNow P2Y12 and short Thrombelastography (TEG) to assess 900 mg doses in (i) initial poor responders to 600 mg and (ii) in a randomised comparison with 600 mg. Blood was taken before and six hours post clopidogrel in (i) 30 volunteers receiving 600 mg (poor responders received 900 mg > two weeks later) and (ii) 60 patients randomized 1 : 1 to 600 mg or 900 mg doses. Poor response was defined as TEG %Clotting Inhibition (%CIn) or VerifyNow Platelet Response Unit (PRU) reduction <30%. (i) Poor responders to 600 mg had greater PRU reduction (45.0 versus 20.1%, P = 0.03) and greater %CIn (22.9 versus -15.1%, P = 0.01) after 900 mg but (ii) there were no significant differences between the patient groups. Near-patient assessment of response to clopidogrel is feasible and clinically useful. Whilst ineffective on a population basis 900 mg doses increase the effect of clopidogrel in initial poor responders.
RESUMO
There is significant variability in both baseline clotting tendency and response to antiplatelet therapy. Responses are associated with outcome. We have investigated whether differences could explain the increased risk observed in women presenting with coronary artery disease. We have utilized short thrombelastography to assess (i) baseline clotting responses, (ii) response to aspirin and clopidogrel, and (iii) post-treatment platelet reactivity in 48 young volunteers, 22 older patients and 18 patients with previous stent thrombosis. Baseline responses were significantly higher in young women than in men. While there was no difference in response to aspirin, platelet reactivity on aspirin remained higher in women (area under curve at 15 min [AUC15] of arachidonic acid channel 332 +/- 122 vs. 172 +/- 80, P= 0.04). Young women had less response to clopidogrel (% reduction in AUC15 with adenosine diphosphate [ADP] 36.4 +/- 12.4 vs. 64.0 +/- 13.2, P < 0.01) in addition to higher post-treatment reactivity (AUC15 of ADP 714 +/- 161 vs. 311 +/- 146, P < 0.01) compared to men. There were no such differences between male and female patients over 50. However, young women with previous stent thrombosis had among the highest platelet reactivity observed. Compared to men, young women have greater baseline clotting tendency, reduced response to clopidogrel, and greater post-treatment reactivity while on both aspirin and clopidogrel. Differences in clotting tendency and response to antiplatelet therapy may contribute to the excess risk observed in young women but are not observed in older female patients.
Assuntos
Aspirina/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Tromboelastografia/métodos , Ticlopidina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Ticlopidina/farmacologiaRESUMO
The most widely accepted methods of assessing response to clopidogrel involve isolated ADP-induced platelet aggregation. Whilst poor response determined by these assays correlates with adverse clinical events, the number of "poor responders" is far higher than the number of events attributed to treatment failure. Clopidogrel may have effects that cannot be assessed using isolated ADP-induced aggregation. We have investigated the effect of clopidogrel on Arachidonic Acid (AA) induced platelet activation-an "aspirin specific" pathway using a novel near patient assay. Thirty four volunteers on no medication and 36 patients, on maintenance therapy with aspirin 75 mg daily, were recruited. Blood tests for Thrombelastogram PlateletMapping were taken immediately prior to and 6 hours after administration of a 600 mg clopidogrel loading dose. Changes in the area under the response curve at 15 minutes (AUC15) with both ADP- and AA-stimulation were calculated as were the corresponding percentage platelet and percentage clotting inhibition (%PIn and %CIn). There were predictable and significant changes in the AUC15 of the ADP channel in response to clopidogrel and the corresponding %PIn and %CIn in both volunteers and patients. There were also significant reductions in the AUC15 of the AA channel (presented as Mean +/- 95%CI), by 27.2 +/- 11.8%, p = 0.005 in volunteers and 35.0 +/- 8.2%, p < 0.001 in patients) and increases in the %PIn and %CIn calculated using the AA channel in volunteers (by 20.0 +/- 11.4%, p + 0.02 and 32.3 +/- 12.8%, p < 0.001 respectively) and patients (by 24.2 +/- 8.6%, p < 0.001 and by 18.0 +/- 8.6, p < 0.001 respectively). Clopidogrel has both independent and aspirin-synergistic effects on AA-induced platelet activation suggesting potentiation of the antiplatelet activity of aspirin. This effect may be clinically important and is not detected by current "gold standard" methods of assessing response to clopidogrel.
Assuntos
Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Ticlopidina/análogos & derivados , Difosfato de Adenosina/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Ácido Araquidônico/farmacologia , Clopidogrel , Interações Medicamentosas , Feminino , Humanos , Masculino , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/farmacologiaRESUMO
AIMS: We conducted a prospective observational study using a course of steroids and antihistamines to treat a cohort of patients who developed skin reactions to clopidogrel, to assess whether dual antiplatelet therapy could be continued in an outpatient setting. METHODS AND RESULTS: This study included 2,701 patients who underwent percutaneous coronary intervention (PCI) at our centre over a 23 month period. Patients with skin reactions to clopidogrel were identified and then commenced on five days oral prednisolone (30 mg/od) and chlorpheniramine (4 mg/tds) for seven days. A subsequent telephone survey was performed to evaluate a number of variables. The probability of the adverse reaction being secondary to clopidogrel was assessed using the Naranjo adverse drug reaction probability scale. Twenty (0.7%) patients were identified who developed adverse skin reactions to clopidogrel. There was complete resolution seen in the majority (89%) of patients within an average of 3.2 days following treatment. One patient had partial resolution, and one had no response to treatment, but both were able to continue clopidogrel. CONCLUSIONS: We propose a novel, safe and effective way of managing clopidogrel-induced skin reactions using a short course of prednisolone and chlorpheniramine, without stopping or substituting clopidogrel.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Dermatopatias/induzido quimicamente , Ticlopidina/análogos & derivados , Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Clorfeniramina/uso terapêutico , Clopidogrel , Stents Farmacológicos , Humanos , Prednisolona/uso terapêutico , Probabilidade , Dermatopatias/tratamento farmacológico , Ticlopidina/efeitos adversosAssuntos
Angioplastia Coronária com Balão , Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Stents , Ticlopidina/análogos & derivados , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Aspirina/efeitos adversos , Doenças Cardiovasculares/etiologia , Clopidogrel , Stents Farmacológicos , Hemorragia/induzido quimicamente , Humanos , Seleção de Pacientes , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Guias de Prática Clínica como Assunto , Desenho de Prótese , Medição de Risco , Tromboelastografia , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Resultado do TratamentoRESUMO
Stent thrombosis is a potentially catastrophic complication of coronary artery stenting. There have been particular concerns about the incidence of stent thrombosis following insertion of drug-eluting stents. We report a series of cases in which stent thrombosis occurred in association with malignancy and describe the potential mechanisms behind such an association. We speculate that this association merits further investigation as it raises the possibility that known malignancy may be a risk factor for stent thrombosis and that unexplained stent thrombosis, particularly if recurrent, should stimulate a search for occult malignancy.