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#46
12.04.2007, 00:43
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Результаты каких исследований по антитромботикам в кардиологии следует ожидать на следующих конференциях (выборочно):
Клопидогрел The ongoing CURRENT/OASIS-7 (Clopidogrel optimal loading dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS) trial will evaluate whether high-dose clopidogrel achieves better clinical outcomes than standard dose in 14,000 NSTE-ACS patients undergoing PCI. Patients randomized to the high dose will receive a 600-mg loading dose then 150-mg daily maintenance dose from day 2 to day 7; patients randomized to the standard dose will receive a 300-mg loading dose then 75-mg daily maintenance dose from day 2 to day 7; from day 8 to day 30, all patients will receive clopidogrel 75 mg daily. In addition, all patients will get randomized to receive aspirin low dose (75 to 100 mg) or high dose (300 to 325 mg); regardless of randomized allocation to high- or low-dose aspirin, all patients will receive aspirin ≥300 mg on day 1. Other ongoing studies evaluating a 600-mg clopidogrel loading dose regimen include ARMYDA-4, which will determine the clinical benefit of a further loading dose of 600-mg clopidogrel pre-PCI in patients already on chronic treatment, and ARMYDA-5, which will assess clinical outcomes of patients undergoing PCI with a pre-loading strategy of 600-mg clopidogrel 4 to 8 h before PCI versus in-lab administration of a 600-mg loading dose after coronary angiography, immediately pre-PCI. The latter will address a highly debated issue in daily clinical practice, which is the problem of knowing coronary anatomy before giving the drug. Празугрел A single oral administration of prasugrel produces a dose-related inhibition of platelet aggregation in rats approximately 10- and 100-fold more potent than that of clopidogrel and ticlopidine, respectively. Better degrees of platelet inhibition have also been confirmed in patients with coronary artery disease (80). The antiaggregatory effects of prasugrel are evident at 30 min and last until 72 h after dosing, indicating fast onset and long duration of action. The ongoing TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel)–TIMI-38 phase III trial will compare prasugrel and clopidogrel in over 13,000 patients with ACS undergoing PCI with the primary end point of death, myocardial infarction, and stroke at 12 months. An additional study, the PRINCIPLE (Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation)–TIMI-44, is currently comparing the relative potency of prasugrel with a higher loading dose (600 mg) and maintenance dose (150 mg daily) of clopidogrel by assessing measures of platelet function, inflammation, and myocyte necrosis in patients undergoing elective PCI. AZD6140 is the first oral reversible ADP receptor antagonist. It is a non-thienopyridine that belongs to a new chemical class called cyclopentyl-triazolo-pyrimidine. AZD6140 does not require hepatic metabolism for its activity and directly inhibits the P2Y12 receptor (82). Platelet aggregation studies have shown that AZD6140 blocks platelet reactivity more consistently and completely than clopidogrel with a lower degree of interindividual response variability (83). The DISPERSE 2 (Safety, Tolerability and Preliminary Efficacy of AZD6140, the First Oral Reversible ADP Receptor Antagonist, Compared with Clopidogrel in Patients with Non–ST-Segment Elevation Acute Coronary Syndrome) was a phase II trial comparing AZD6140 with clopidogrel in patients (n = 990) with ACS that showed similar rates of bleeding in all groups (primary end point: total major/minor bleeding events at 4 weeks) and no significant difference in the composite end point of cardiovascular death, stroke, or recurrent ischemia (84). The ongoing PLATO (A Study of Platelet Inhibition and Patient Outcomes) phase III clinical trial is comparing AZD6140 and clopidogrel in ACS patients with the primary end point of death, myocardial infarction, and stroke at 12 months. Cangrelor (also known as AR-C69931MX) is also a selective and competitive P2Y12 antagonist, which is suitable for intravenous administration (85). Cangrelor is an ATP analogue, with more potent antiplatelet activity than clopidogrel (90% inhibition of platelet aggregation at 1 to 4 μg/kg/min intravenous) that leads to selective inhibition of ADP-induced aggregation in a dose-dependent manner. Importantly, there is a rapid reversal of its dose-dependent effects. Reports from phase II clinical trials show that cangrelor in addition to tissue-type plasminogen activator in patients with STEMI is associated with a greater degree of ST-segment recovery in a dose-dependent manner (85). Further, in patients undergoing PCI, cangrelor compares favorably with abciximab both from a safety and clinical standpoint. Two phase III trials with cangrelor (CHAMPION PCI and CHAMPION PLATFORM) are currently ongoing. (J Am Coll Cardiol. 2007 Apr 10;49(14):1505-16) 
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#47
12.04.2007, 09:31
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по теме: Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. [Ссылки доступны только зарегистрированным пользователям ]
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#48
14.05.2007, 21:52
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В текущем номере JAMA 2007 May 9;297(18):1985-91 появилась публикация об исследовании SWISSI II, которое было представлено на конференции ACC'2007
Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial. Erne P, и соавт. Тезисы: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006. INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin. MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up. RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events.
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#49
14.05.2007, 23:53
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Цитата:
2. Общая смертность не отличалась между группами (6/1019 против 22/1048) 3. Верификация ишемии вызывает вопросы: ВЭМ и далее при положительной пробе - стресс-ЭхоКГ или нагрузочная сцинтиграфия 4. Не указан процент пациентов на статинах, плавиксе и ингибиторах АПФ (видимо, мало) 5. Стенты использовались редко 6. Пациентов откровенно мало, хотя срок наблюдения приличный 7. В группе лекарственной терапии отсутствовал чёткий алгоритм лечения. Основная цель - исчезновение "немой" ишемии по данным ВЭМ. При этом могли использоваться Б-блокаторы, антогонисты кальция, молсидомин или их комбинация. Статья в свободном доступе [Ссылки доступны только зарегистрированным пользователям ]
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