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#77
21.01.2007, 23:06
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#78
21.01.2007, 23:29
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Извините за назойливость...если я Вас правильно поняла, то в Вашей клинике определение резистентности к плавиксу считается более важным, чем к аспирину? Хотелось бы узнать почему...
И как возможно преодолеть резистентность к аспирину? Так же за счет увеличения дозы? Профессором Грацианским на одном из последних заседаний кардиологического общества приведены данные об увеличении нагрузочной дозы плависка с обычных 600 до 900 и даже до 1200мг в случае эксренной PCI...
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#79
22.01.2007, 19:24
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#80
22.01.2007, 22:17
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In an earlier crossover study of healthy volunteers, we compared different preparations of aspirin at low doses and found that enteric-coated (EC) aspirin was less effective than plain aspirin. This difference was most obvious in heavier patients (11). 11 D. Cox, A. O. Maree, M. Dooley, M. F. Byrne, R. Conroy and D. J. Fitzgerald, Lower bioavailability and weight dependence of enteric-coated aspirin preparations (abstr), Arterioscler Thromb Vasc Biol 24 (2004), p. e53 Цитировано из Stroke. 2006 Aug;37(8):2153-8. Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers. Cox D, и соавт. ...Using logistic regression analysis an 80-kg subject had a 20% probability of treatment failure. Asasantin was the most potent preparation in terms of inhibition of platelet aggregation. CONCLUSIONS: Equivalent doses of the enteric-coated aspirin were not as effective as plain aspirin. Lower bioavailability of these preparations and poor absorption from the higher pH environment of the small intestine may result in inadequate platelet inhibition, particularly in heavier subjects.
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#81
22.01.2007, 23:53
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Есть и такое мнение...
[Ссылки доступны только зарегистрированным пользователям ] 2006 May;151(5):976.e7-11. Lack of effect of enteric coating on aspirin-induced inhibition of platelet aggregation in healthy volunteers. [Ссылки доступны только зарегистрированным пользователям ] et al. Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. BACKGROUND: Aspirin inhibits platelet aggregation and is widely used in the treatment of cardiovascular disease. Some individuals are less responsive to aspirin's antiplatelet effect, a phenomenon termed aspirin resistance. It is not known whether the antiplatelet effect is fully preserved with the enteric-coated (EC) formulation. METHODS: We performed a prospective randomized trial of 50 healthy volunteers using a crossover design to compare the EC with the standard aspirin formulations. The subjects received a 7-day course of each aspirin formulation (81-mg) (Bayer Corporation, Morristown, NJ) separated by a 3-week washout period. Platelet function was measured before and after each course using optical aggregometry (with arachidonic acid and adenosine diphosphate as agonists) and a point-of-care platelet assay. RESULTS: The assays were reproducible, and the variation in baseline platelet function was small to moderate between the subjects. There was no difference in the extent of platelet inhibition between the EC and standard formulations with any of the 3 assays. With the point-of-care platelet assay, the mean aspirin effect favoring the standard formulation (more aggregation inhibition) compared with the EC formulation was 1.6% +/- 15.8% (P = .60 for difference between the formulations). The corresponding optical aggregometry values were -3.4% +/- 39.5% (P = .97) and -1.4% +/- 16.6% (P = .75) for arachidonic acid and adenosine diphosphate, respectively. CONCLUSIONS: Compared with standard aspirin, EC aspirin appears to exhibit similar inhibition of platelet aggregation in healthy volunteers. Furthermore, point-of-care platelet assessment correlated well with the gold standard of laboratory-based optical platelet aggregometry.
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#82
23.01.2007, 00:43
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Все это зависит от того, как оценивался аспириновый эффект: по тромбоцитарной агрегации или угнетению синтеза тромбоксана, последний параметр тоже может отличаться по интерпретации - угнетение синтеза на >95% или на >99% (все парамерты показали свою прогностич. значимость, но какой из них более значим?) Эксперты считают, что тромбоксановое угнетение более специфично для термина "аспириновая резистентность":
Failure of Aspirin to Inhibit TxA2 Production Lacking a reproducible and highly sensitive and specific method to study TxA2-dependent platelet function, the pharmacological response to aspirin treatment should be assessed by measuring the degree of inhibition of TxA2 production. This could be performed by measuring either serum TxB2 or the urinary excretion of TxB2 metabolites. Therefore, based on the available techniques, the only acceptable definition of aspirin resistance should rely on the demonstration of an insufficient inhibition of TxA2 production. For the sake of clarity, in the remaining part of this review, I refer to failure of aspirin to inhibit TxA2 production with the term "true" aspirin resistance, and to failure of aspirin to inhibit platelet function "in vivo" or "in vitro" (without demonstration of inadequate inhibition of TxA2 production) with the term "unproven" aspirin resistance. Подробнее [Ссылки доступны только зарегистрированным пользователям ] Напоследок из недавнего консенсуса по аспиринорезистентности J Thromb Haemost. 2005 Jun;3(6):1309-11: Possible mechanisms of aspirin 'resistance' Bioavailability Non-compliance Underdosing Poor absorption (enteric coated aspirin) Interference: NSAID coadministration Platelet function Incomplete suppression of thromboxane A2 generation Accelerated platelet turnover, with introduction into bloodstream of newly formed, drug-unaffected platelets Stress-induced COX-2 expression in platelets Increased platelet sensitivity to ADP and collagen Single nucleotide polymorphisms Receptors: GPIIb-IIIa, collagen receptor, thromboxane receptor, etc. Enzymes: COX-1, COX-2, thromboxane A2 synthase, etc. Platelet interactions with other blood cells Endothelial cells and monocytes provide PGH2 to platelets (bypassing COX-1) and also synthesize their own thromboxane A2 Other factors Smoking, hypercholesterolemia, exercise, stress, etc. Rather than 'resistance', is it: Aspirin response variability? Platelet response variability? Treatment failure (because arterial thrombosis is multifactorial)?
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#83
12.04.2007, 18:34
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Правильная терапия резистентности к аспирину, если она существует, неизвестна. Ни в одном из опубликованных исследований не изучалась эффективность изменения терапии на основании лабораторного выявления «резистентности» к аспирину. Поэтому вне научных исследований в настоящее время не следует ни применять тесты на «резистентность» к аспирину у больных, ни изменять терапию на основании таких тестов. Требуется дать имеющее клинический смысл определение резистентности к аспирину, основанное на данных о связи [результатов] лабораторных тестов, отражающих действие аспирина, и клинических исходов у пациентов. а вот еще интересная ссылка" диспут об аспирине подогревается средствами соперничающих компаний" Wall street journal- [Ссылки доступны только зарегистрированным пользователям ] (подписчики могут прочитать  )Что касается дозы увеличения дозы плавикса при PCI - так это для ускорения его антитромбоцитарного действия,а не с целью преодоления мнимой резистентности. При желании в лабораторных условиях, на том же агрегометре BIOLA очень несложно получить кривую под 100% т.е. выявить пациента с гиперрезистентностью к аспирину.(просто добавьте чуть больше индуктора,...на одну капельку...ну скажем той же АДФ ).Концентрации же АДФ используемые при проведении агрегометрии для выявления резистентности к клопидогрелю in vitro чрезмерны- это по сути седиментация тромбоцитов, ( в пробирке образуется этакий единый конгломерат из тромбоцитов,) а не агрегация. Dr.Vad разместил великолепную ссылку,(Респект.по-моему она в свободном доступе.)Составили этот position paper все те ученые люди,кто когда -то занимался исследованием резистентности к аспирину. я надеялся что этот документ - последний гвоздь в крышку гроба резистентностям , а ннннеееет  сорри за оффтоп
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#84
12.04.2007, 18:46
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Cardiology at Careggi Hospital, Florence, Italy, presented data showing a mortality rate of 11.4 percent for non responders to antiplatelet agents versus 1.4 percent for responders. Dr. Lasala said this suggests interventionalists should routinely measure platelet aggregation in their patients because non-responders apparently require more aggressive followup and treatment.
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#85
12.04.2007, 19:12
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А в исследованиях CURRENT/OASIS-7 и ARMYDA-4-5 все равно тестируется б0льшая доза клопи против меньшей без "опирания на агрегацию", несмотря на то, что у больных с клопи-резистентностью худший прогноз был замечен еще 3-4 года назад. Значит, не все так гладко с воспроизводимостью техники в мировом масштабе, хотя верю, что в этой Флорентийской клинике агрегацию меряют как гемоглобин; жаль, что Док.Ласала на конференции не поделился собственным опытом применения более агрессивной антитромботич. терапии после выявления резистентности...
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#86
12.04.2007, 23:10
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#87
13.04.2007, 18:55
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#88
13.04.2007, 23:17
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Long-Term Safety of DES in Off-Label Use: Results of the MATRIX Registry
MATRIX is a prospective single-arm study initiated in 2004 to evaluate the impact of SES implants in a consecutive "real world" population. Investigators assessed both on- and off-label use, the impact of SES implantation on the incidence of TLR, and the occurrence of early (30 day) and late (6 month, 1 year, and 2 years so far) major acute cardiovascular events (MACE). This consecutive series of 1,522 patients included patients with diabetes (33.8%) or a history of heart attack (33.4%), balloon angioplasty (44.6%), or bypass surgery (21%).
The study used a definition of stent thrombosis recently proposed (October 2006) by the Academic Research Consortium (ARC). The definition was designed to eliminate variability in what gets labeled “stent thrombosis” across different drug-eluting stent trials. In the MATRIX registry, investigators recommended use of aspirin and clopidogrel for 1 year for all patients, with physician discretion thereafter. According to principal investigator George D. Dangas, MD, FACC, off-label use was evident in 86% of patients. However, considering the complexity of patients and lesions treated, there was a low incidence of early and late adverse events, including 2-year mortality (3.3%) and 2-year incidence of MI (4.0%) There were encouragingly low rates of composite endpoints, too, such as death/MI (6.8%). Importantly, mortality was similar for both on- and off-label use, and multivariate analysis indicated that off-label use was not an independent predictor of mortality. The 2-year rate of stent thrombosis was 1.1%, based on the ARC definition of “definite/probable” thrombosis and independent event adjudication. There was a big difference between what was recommended in terms of medication and what was actually achieved in clinical practice. As noted, MATRIX investigators recommended dual antiplatelet therapy for at least 1 year. Interruption would occur for a clinical reason or by physician choice based on factors such as individual patient risk. Despite these recommendations, only 80% of patients were on clopidogrel at 6 months, and adherence was just 61% at 2 years. Adherence to aspirin was more consistent, with not quite 90% of patients still taking aspirin at 2 years. What do the data tell us? According to Dr. Dangas, patients with higher-risk features may have been the ones who remained on clopidogrel. This is based on the significantly higher rates of revascularization in the on-clopidogrel group, suggesting greater adherence to dual antiplatelet therapy in patients who were recognized as more complex than other patients, who were taken off clopidogrel therapy. Besides the difference in revascularization rates, no other outcomes varied by whether patients did or did not remain on clopidogrel therapy.
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#89
13.04.2007, 23:20
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продолжение
Interpretation
How does the 1.1% thrombosis rate in MATRIX compare with data from other trials? Dr. Dangas said, “Given the very strict definitions used, as well as the independent committee that adjudicated the events, I think this percentage is rather low and very encouraging.” He added, “It's important to say that in the multivariate analysis, the predictors of death, MI, [and] target vessel revascularization were predominantly high-risk patients, lesion characteristics, and variables such as age, diabetes, chronic renal failure, and hemodialysis, as opposed to off-label use or other more technical characteristics.” Like others, the MATRIX investigators are concerned about late stent thrombosis, so they plan to continue patient follow-up for 5 years, with annual reports of long-term outcome. Given the well defined core population, the generally accepted definitions of thrombosis, and a sizable population of patients remaining on clopidogrel therapy, Dr. Dangas said there may still be much to learn from this registry, particularly regarding low frequency, long-term safety endpoints such as late stent thrombosis. Second Opinion Alfred A. Bove, MD, PhD, FACC: The MATRIX Registry confirms that the application of drug-eluting stents has been extended in practice well beyond the approved indications. It’s encouraging that outcomes were similar whether these stents were used on- or off-label, but of course there are no data in this registry that compare the results with BMS placement. The study coordinators have helped by limiting two important variables that have contributed to the conflicting data of the last year: they have clearly defined stent thrombosis and have analyzed the data to account for key differences in the characteristics of patients and coronary lesions. One concern: it’s discouraging to see so many patients not being treated to the guidelines in terms of dual antiplatelet therapy. While situations occur that make it difficult to maintain recommended antiplatelet therapy, clopidogrel should continue for at least 12 months in patients with DES who are at low risk of bleeding, and alternative strategies should be considered in patients unable to tolerate uninterrupted dual antiplatelet therapy. [Ссылки доступны только зарегистрированным пользователям ]
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#90
03.05.2007, 09:59
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"Офф-топ" по теме...
Не везет мне с сайферами...  Сегодня "очередной" тромбоз (LST): пациент 60 лет, в дистальном сегменте стентированной ПМЖА (два сайфера по 18 мм.), теперь уже через два года и два месяца (на фоне "свободности" от стенокардии, после бассейна и бани, без плавикса) [Ссылки доступны только зарегистрированным пользователям ] [Ссылки доступны только зарегистрированным пользователям ] [Ссылки доступны только зарегистрированным пользователям ] [Ссылки доступны только зарегистрированным пользователям ] ...
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Линейный вид
