4/27/2023 0 Comments Timi americaHowever, pauses were rarely associated with symptoms, and the treatment groups did not differ significantly with respect to the incidence of syncope or pacemaker implantation. 2,6 In the first week of treatment, a higher incidence of ventricular pauses was observed with ticagrelor compared with clopidogrel. 0.1%) and no effect of ticagrelor on pulmonary function was seen in a substudy of PLATO. 7.8%), although few patients discontinued treatment due to dyspnea (0.9% vs. 2 Dyspnea was more common in the ticagrelor group than in the clopidogrel group (13.8% of patients vs. 2 Ticagrelor did not increase the rate of overall major bleeding, but a statistically significant increase in noncoronary artery bypass grafting (non-CABG) major bleeding (4.5% vs. 6.9% with clopidogrel, P = 0.005), death from vascular causes (4.0% vs. Predefined hierarchical testing of individual secondary efficacy end points showed ticagrelor was associated with significant reductions in rates of MI (5.8% with ticagrelor vs. 2 At 12 months, ticagrelor significantly reduced the primary end point. In the PLATO trial ( Table 1), 18,624 patients with ACS were randomized to ticagrelor (180 mg loading dose, 90 mg twice-daily maintenance dose) or clopidogrel (300–600 mg loading dose, 75 mg/d maintenance dose). This may help to optimize the use of these drugs and to target treatment to the patient populations deriving most benefit. This review examines the similarities and differences between the design of PLATO, TRITON-TIMI-38, and TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY-ACS), and assesses whether cross-trial comparisons are appropriate in the case of ticagrelor and prasugrel. The validity of such adjusted indirect comparisons depends on a number of factors, including the overall similarities of the study designs, hospital setting, inclusion/exclusion criteria, treatment strategies, study duration, and end point definitions. Elsewhere, Biondi-Zoccai et al 1 undertook a clopidogrel-adjusted comparative meta-analysis of ticagrelor versus prasugrel using data from the PLATelet inhibition and patient Outcomes (PLATO), DISPERSE-2, and TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel–Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 studies. There are no available data from direct head-to-head clinical comparisons of ticagrelor and prasugrel, although the ongoing ISAR-REACT-5 trial (NCT01944800) aims to evaluate whether ticagrelor is superior to prasugrel in patients with ACS for whom an invasive treatment strategy is planned. However, these clinical decisions can be difficult in the absence of head-to-head trials that definitively demonstrate a treatment benefit of one agent over another.Ĭlinical decision making based on cross- trial comparison is an important issue for the antiplatelet drugs ticagrelor and prasugrel, as both have shown superiority over clopidogrel in the treatment of patients with acute coronary syndromes (ACS), but in separate studies. In clinical practice, physicians frequently base their decisions on data from well-controlled, randomized, comparative clinical trials. In conclusion, this information, along with the current guidelines and recommendations, will assist clinicians in deciding the most appropriate treatment pathway for their patients with NSTE-ACS and STEMI. Here, we describe each of these trials in detail and explain the differences between them that make direct comparisons difficult. These differences are clearly reflected in the most recent updates to the European Society of Cardiology (ESC) non-ST elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) guidelines, which include recommendations for the use of the antiplatelet agents ticagrelor, prasugrel, and clopidogrel, based in part on results from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel–Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38, TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY-ACS) and PLATelet inhibition and patient Outcomes (PLATO) trials. Cross-trial comparisons are typically inappropriate as there are often numerous differences in study designs, populations, end points, and loading doses of the study drugs.
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