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Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial

JAMES, Stefan; ANGIOLILLO, Dominick J.; CORNEL, Jan H.; ERLINGE, David; HUSTED, Steen; KONTNY, Frederic; MAYA, Juan; NICOLAU, Jose C.; SPINAR, Jindrich; STOREY, Robert F.; STEVENS, Susanna R.; WALLENTIN, Lars; PLATO Study Grp
Fonte: OXFORD UNIV PRESS Publicador: OXFORD UNIV PRESS
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
38%
Patients with diabetes mellitus (DM) have high platelet reactivity and are at increased risk of ischaemic events and bleeding post-acute coronary syndromes (ACS). In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor reduced the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke, but with similar rates of major bleeding compared with clopidogrel. We aimed to investigate the outcome with ticagrelor vs. clopidogrel in patients with DM or poor glycaemic control. We analysed patients with pre-existing DM (n = 4662), including 1036 patients on insulin, those without DM (n = 13 951), and subgroups based on admission levels of haemoglobin A1c (HbA1c; n = 15 150). In patients with DM, the reduction in the primary composite endpoint (HR: 0.88, 95% CI: 0.76-1.03), all-cause mortality (HR: 0.82, 95% CI: 0.66-1.01), and stent thrombosis (HR: 0.65, 95% CI: 0.36-1.17) with no increase in major bleeding (HR: 0.95, 95% CI: 0.81-1.12) with ticagrelor was consistent with the overall cohort and without significant diabetes status-by-treatment interactions. There was no heterogeneity between patients with or without ongoing insulin treatment. Ticagrelor reduced the primary endpoint, all-cause mortality...

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

James, Stefan K.; Storey, Robert F.; Khurmi, Nardev S.; Husted, Steen; Keltai, Matyas; Mahaffey, Kenneth W.; Maya, Juan; Morais, Joao; Lopes, Renato D.; Nicolau, Jose C.; Pais, Prem; Raev, Dimitar; Lopez-Sendon, Jose L.; Stevens, Susanna R.; Becker, Richa
Fonte: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA Publicador: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
37.83%
Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases...

Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor Insights From the Platelet Inhibition and Patient Outcomes Trial

Goodman, Shaun G.; Clare, Robert; Pieper, Karen S.; Nicolau, José C.; Storey, Robert F.; Cantor, Warren J.; Mahaffey, Kenneth W.; Angiolillo, Dominick J.; Husted, Steen; Cannon, Christopher P.; James, Stefan K.; Kilhamn, Jan; Steg, P. Gabriel; Harrington
Fonte: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA Publicador: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
38%
Background-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n = 6539) compared with those not on a PPI (n = 12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI...

Ticagrelor: The First Reversibly Binding Oral P2Y12 Receptor Antagonist

Husted, Steen; van Giezen, JJJ
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em //2009 EN
Relevância na Pesquisa
28.1%
Ticagrelor (AZD6140) is the first reversibly binding oral P2Y12 receptor antagonist that blocks ADP-induced platelet aggregation. Unlike thienopyridines, which irreversibly bind to the P2Y12 receptor for the lifetime of the platelet, ticagrelor binds reversibly to the receptor and exhibits rapid onset and offset of effect, which closely follow drug exposure levels. Animal models indicate greater separation between antithrombotic effects and bleeding effects with ticagrelor than with thienopyridines. Unlike the thienopyridines, ticagrelor does not require metabolic activation. It is quickly absorbed and exhibits a rapid antiplatelet effect, with higher and more consistent levels of inhibition of platelet aggregation (IPA) being maintained across the dosing interval than with clopidogrel. IPA levels decline with plasma drug levels after discontinuation of dosing. In the phase II DISPERSE-2 trial of 990 patients with non-ST-elevation acute coronary syndromes (ACS), ticagrelor treatment with 90 mg and 180 mg twice daily showed comparable rates of major and minor bleeding compared with clopidogrel 75 mg while there were numerically fewer myocardial infarctions. Ticagrelor resulted in greater IPA in clopidogrel-naïve patients and produced substantial additional reductions in platelet aggregation activity in patients pretreated with clopidogrel. Ticagrelor treatment was well tolerated in DISPERSE-2...

Critical appraisal of ticagrelor in the management of acute coronary syndrome

Nawarskas, James J; Snowden, Stanley S
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28.3%
Ticagrelor is a novel P2Y12 receptor antagonist which, like clopidogrel and prasugrel, functions by blocking adenosine diphosphate-mediated platelet aggregation. However, unlike the aforementioned agents, the binding of ticagrelor to this receptor is reversible. Ticagrelor is also believed to mediate some of its beneficial effects by augmenting the effects of adenosine, which is another unique pharmacologic property of this drug. In terms of antiplatelet effect, ticagrelor is more potent than clopidogrel and produces a faster and stronger inhibition of platelet aggregation. This may also be an advantage of ticagrelor over prasugrel, but this has not been adequately studied. Due to the reversible nature of the binding of ticagrelor to the platelet receptor, ticagrelor has a relatively fast offset of effect, with platelet aggregation approaching pretreatment levels about 3 days after discontinuation of therapy. This has advantages in patients requiring invasive procedures, but also makes medication adherence very important in order to be able to maintain an effective antiplatelet effect. Ticagrelor has been shown to be clinically superior to clopidogrel when given to patients with an acute coronary syndrome, resulting in significantly lower rates of myocardial infarction and vascular death. However...

Challenging the FDA Black Box Warning for High Aspirin Dose With Ticagrelor in Patients With Diabetes

DiNicolantonio, James J.; Serebruany, Victor L.
Fonte: American Diabetes Association Publicador: American Diabetes Association
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28%
Ticagrelor, a novel reversible antiplatelet agent, has a Food and Drug Administration (FDA) black box warning to avoid maintenance doses of aspirin (ASA) >100 mg/daily. This restriction is based on the hypothesis that ASA doses >100 mg somehow decreased ticagrelor’s benefit in the Platelet Inhibition and Patient Outcomes (PLATO) U.S. cohort. However, these data are highly postrandomized, come from a very small subgroup in PLATO (57% of patients in the U.S. site), and make no biological sense. Moreover, the ticagrelor-ASA interaction was not significant by any multivariate Cox regression analyses. The Complete Response Review for ticagrelor indicates that for U.S. PLATO patients, an ASA dose >300 mg was not a significant interaction for vascular outcomes. In the ticagrelor-ASA >300 mg cohort, all-cause and vascular mortality were not significantly increased (hazard ratio [HR] 1.27 [95% CI 0.84–1.93], P = 0.262 and 1.39 [0.87–2.2], P = 0.170), respectively. Furthermore, for major adverse cardiovascular events (MACEs), 30-day all-cause mortality, and 30-day vascular mortality, the strongest interaction is the diabetes-ASA interaction. That is, patients who had diabetes had significantly fewer MACEs through study end (0.49 [0.34–0.63]...

High-Dose, but Not Low-Dose, Aspirin Impairs Anticontractile Effect of Ticagrelor following ADP Stimulation in Rat Tail Artery Smooth Muscle Cells

Grześk, Grzegorz; Kozinski, Marek; Tantry, Udaya S.; Wicinski, Michal; Fabiszak, Tomasz; Navarese, Eliano P.; Grzesk, Elzbieta; Jeong, Young-Hoon; Gurbel, Paul A.; Kubica, Jacek
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28.1%
Objective. To compare effects of low- versus high-dose aspirin coadministered with ticagrelor on the reactivity of vascular smooth muscle cells (VSMCs). Methods. Wistar rats were orally administered ticagrelor (10 mg/kg) and/or aspirin (2 or 10 mg/kg) (n = 7 per each of 4 groups) or placebo (n = 9) 12 and 2 hours before experiments. Anticontractile effects of ticagrelor were assessed in perfusion solution containing ticagrelor (1 μM/L). Changes in perfusion pressure proportional to the degree of adenosine diphosphate analogue- (2-MeS-ADP-) and phenylephrine-induced constriction of rat tail arteries were evaluated. Results. Pretreatment with high- but not low-dose aspirin enhanced the reactivity of VSMCs only in endothelium-lined vessels. Suppression of 2-MeS-ADP-induced VSMC contraction by ticagrelor observed in arteries with and without endothelium was maintained in endothelialized arteries pretreated only with low-dose aspirin. For endothelium-denuded vessels and low-dose aspirin we observed a significant reduction of the maximal effect of ticagrelor with no rightward shift of the concentration-response curve for phenylephrine. With high-dose aspirin pretreatment ticagrelor exerted no anticontractile effect. Conclusion. High-dose...

Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers

Teng, Renli; Maya, Juan; Butler, Kathleen
Fonte: Informa UK Ltd. Publicador: Informa UK Ltd.
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28.25%
The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1–5; 200 mg bid Days 6–9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1–10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2–9) with either ticagrelor (200 mg bid Days 4–8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5–9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (C max), median time to C max (t max), or mean area under the plasma concentration-time curve for the dosing interval (AUC0– τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean C max and AUC0– τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However...

Microglia is a key player in the reduction of stroke damage promoted by the new antithrombotic agent ticagrelor

Gelosa, Paolo; Lecca, Davide; Fumagalli, Marta; Wypych, Dorota; Pignieri, Alice; Cimino, Mauro; Verderio, Claudia; Enerbäck, Malin; Nikookhesal, Elham; Tremoli, Elena; Abbracchio, Maria P; Sironi, Luigi
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28.05%
The ADP-responsive P2Y12 receptor is expressed on both platelets and microglia. Clinical data show that ticagrelor, a direct-acting, reversibly binding P2Y12-receptor antagonist, reduces total cardiovascular events, including stroke. In our present study, we investigated the expression of P2Y12 receptors and the effects of ticagrelor on brain injury in Sprague-Dawley rats subjected to a permanent middle cerebral artery occlusion (MCAo). Rats were treated per os with ticagrelor 3 mg/kg or vehicle at 10 minutes, 22, and 36 hours after MCAo and killed after 48 hours. Immunofluorescence analysis showed an ischemia-related modulation of the P2Y12 receptor, which is constitutively expressed in Iba1+ resting microglia. After MCAo, activated microglia was mainly concentrated around the lesion, with fewer cells present inside the ischemic core. Ticagrelor significantly attenuated the evolution of ischemic damage—evaluated by magnetic resonance imaging (MRI) at 2, 24, and 48 hours after MCAo—, the number of infiltrating cells expressing the microglia/monocyte marker ED-1, the cerebral expression of proinflammatory mediators (interleukin 1 (IL-1), monocyte chemoattractant protein 1 (MCP-1), nitric oxide synthase (iNOS)) and the associated neurologic impairment. In transgenic fluorescent reporter CX3CR1-green fluorescent protein (GFP) mice...

Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany

Theidel, Ulrike; Asseburg, Christian; Giannitsis, Evangelos; Katus, Hugo
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28%
The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix® or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3...

Ticagrelor: Pharmacokinetics, Pharmacodynamics, Clinical Efficacy, and Safety

Dobesh, Paul P; Oestreich, Julie H
Fonte: BlackWell Publishing Ltd Publicador: BlackWell Publishing Ltd
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28%
Dual antiplatelet therapy, composed of aspirin plus a P2Y12-receptor antagonist, is the cornerstone of treatment for patients with acute coronary syndrome (ACS). A number of U.S. Food and Drug Administration–approved P2Y12-receptor antagonists are available for treating patients with ACS, including the thienopyridine compounds clopidogrel and prasugrel. Ticagrelor, the first of a new class of antiplatelet agents, is a noncompetitive, direct-acting P2Y12-receptor antagonist. Unlike the thienopyridine compounds, ticagrelor does not require metabolism for activity. Also, whereas clopidogrel and prasugrel are irreversible inhibitors of the P2Y12 receptor, ticagrelor binds reversibly to inhibit receptor signaling and subsequent platelet activation. In pharmacodynamic studies, ticagrelor demonstrated faster onset and more potent inhibition of platelet aggregation than clopidogrel. These properties of ticagrelor may contribute to reduced rates of thrombotic outcomes compared with clopidogrel, as demonstrated in a phase III clinical trial. However, in addition to bleeding, distinctive adverse effects of this new chemical entity have not been reported with the thienopyridine P2Y12-receptor inhibitors. Although ticagrelor represents an advancement in P2Y12-receptor inhibition therapy...

A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in Hispanic patients with stable coronary artery disease

Price, Matthew J.; Clavijo, Leonardo; Angiolillo, Dominick J.; Carlson, Glenn; Caplan, Richard; Teng, Renli; Maya, Juan
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28.05%
The objective was to compare the pharmacodynamic (PD) and pharmacokinetic (PK) effects of ticagrelor with clopidogrel among subjects of Hispanic ethnicity, as the PD and PK effects of antiplatelet agents among Hispanics are not specifically known. This was a randomised, open-label, crossover PD/PK study of 40 Hispanic subjects with stable coronary artery disease (CAD). Subjects were allocated to either ticagrelor 180 mg loading dose (LD)/90 mg twice-daily maintenance dose (MD) followed by clopidogrel 600 mg LD/75 mg once-daily MD with an intervening washout period, or vice versa. The primary endpoint was on-treatment reactivity (OTR) at 2 h post-LD according to the VerifyNow P2Y12 test. OTR was significantly lower at 2 h post-LD with ticagrelor compared with clopidogrel (34 PRU vs. 201 PRU, least square means difference = −167 PRU [95 % CI, −197, −137], P < 0.001). OTR was also lower with ticagrelor at 30 min and 8 h post-LD (P < 0.001). The greater magnitude of antiplatelet effect with ticagrelor persisted after 7 days of MD (52 PRU [95 % CI, 30, 73] vs. 182 PRU [95 % CI, 160, 205], P < 0.001). Mean plasma concentration of ticagrelor and its active metabolite were greatest at 2 h post-LD, with similar levels at 2 h post-MD after 7 days of MD. Among Hispanic subjects with stable CAD...

An open-label, randomized bioavailability study with alternative methods of administration of crushed ticagrelor tablets in healthy volunteers

Teng, Renli; Carlson, Glenn; Hsia, Judith
Fonte: Dustri-Verlag Dr. Karl Feistle Publicador: Dustri-Verlag Dr. Karl Feistle
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
28.14%
Objective: To compare the bioavailability and safety profile of crushed ticagrelor tablets suspended in water and administered orally or via nasogastric tube, with that of whole tablets administered orally. Methods: In this single-center, open-label, randomized, three-treatment crossover study, 36 healthy volunteers were randomized to receive a single 90-mg dose of ticagrelor administered orally as a whole tablet or as crushed tablets suspended in water and given orally or via a nasogastric tube into the stomach, with a minimum 7-day wash-out between treatments. Plasma concentrations of ticagrelor and AR-C124910XX were assessed at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-ticagrelor dose for pharmacokinetic analyses. Safety and tolerability was assessed throughout the study. Results: At 0.5 hours postdose, plasma concentrations of ticagrelor and AR-C124910XX were higher with crushed tablets administered orally (148.6 ng/mL and 13.0 ng/mL, respectively) or via nasogastric tube (264.6 ng/mL and 28.6 ng/mL, respectively) compared with whole-tablet administration (33.3 ng/mL and 5.2 ng/mL, respectively). A similar trend was observed at 1 hour postdose. Ticagrelor tmax was shorter following crushed vs. whole-tablet administration (1 vs. 2 hours...

Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis

Alsharif, Khalaf F.; Thomas, Mark R.; Judge, Heather M.; Khan, Haroon; Prince, Lynne R.; Sabroe, Ian; Ridger, Victoria C.; Storey, Robert F.
Fonte: Elsevier Science Publicador: Elsevier Science
Tipo: Artigo de Revista Científica
Publicado em /08/2015 EN
Relevância na Pesquisa
28.14%
In the PLATO study, ticagrelor was associated with fewer pulmonary infections and subsequent deaths than clopidogrel. Neutrophils are a first-line defence against bacterial lung infection; ticagrelor inhibits cellular uptake of adenosine, a known regulator of neutrophil chemotaxis and phagocytosis. We assessed whether the inhibition of adenosine uptake by ticagrelor influences neutrophil chemotaxis and phagocytosis. Neutrophils and erythrocytes were isolated from healthy volunteers. Concentration-dependent effects of adenosine on IL-8-induced neutrophil chemotaxis were investigated and the involved receptors identified using adenosine receptor antagonists. The modulatory effects of ticagrelor on adenosine-mediated changes in neutrophil chemotaxis and phagocytosis of Streptococcus pneumoniae were determined in the presence of erythrocytes to replicate physiological conditions of cellular adenosine uptake. Low-concentration adenosine (10− 8 M) significantly increased IL-8-induced neutrophil chemotaxis (% neutrophil chemotaxis: adenosine 28.7% ± 4.4 vs. control 22.6% ± 2.4; p < 0.01) by acting on the high-affinity A1 receptor. Erythrocytes attenuated the effect of adenosine, although this was preserved by ticagrelor and dipyridamole (another inhibitor of adenosine uptake) but not by control or by cangrelor. Similarly...

Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy

Janzon, M; James, S; Cannon, C P; Storey, R F; Mellström, C; Nicolau, J C; Wallentin, L; Henriksson, M
Fonte: BMJ Publishing Group Publicador: BMJ Publishing Group
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
28%
Objective: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. Methods: A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. Results: Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish...

Efeito dos novos antiagregantes plaquetários prasugrel e ticagrelor administrados upstream sobre os achados angiográficos da angioplastia primária; Effect of new antiplatelet prasugrel and ticagrelor upstream therapy, on angiographic results of primary percutaneous coronary intervention

Mont'Alverne Filho, José Ronaldo
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 03/08/2015 PT
Relevância na Pesquisa
28.27%
Introdução. A dupla antiagregação plaquetária traz benefícios no tratamento do infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMSST). Há variabilidade intra e interindividual no uso do clopidogrel e isso influencia no benefício do seu uso nesse grupo de pacientes. O objetivo desta pesquisa foi avaliar os efeitos de novo antiagregantes plaquetários (prasugrel e ticagrelor) administrados na sala de emergência ("upstream") sobre o resultado angiográfico da angioplastia primária, levando em conta o fluxo coronariano TIMI, o blush miocárdico e a carga de trombo. Métodos. Foi realizado um ensaio clínico, randomizado, cego, com 131 pacientes admitidos com IAMSST. Todos os pacientes receberam ácido acetilsalicílico (AAS). Os pacientes foram randomizados para receber clopidogrel (n=44), prasugrel (n=41) ou ticagrelor (n=46) como dose de ataque ainda na emergência. Todos os pacientes foram submetidos a aspiração manual de trombos. Ao término do procedimento, o resultado angiográfico foi avaliado quanto ao fluxo TIMI, o blush miocárdico e a carga de trombo. Resultados. O fluxo coronariano TIMI >= 1 antes do procedimento foi observado mais frequentemente com o uso de ticagrelor (n = 10, 21,7%) do que com o clopidogrel (n = 1...

Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes; Avaliação Económica de Ticagrelor em Prevenção Secundária Pós Síndroma Coronária Aguda

Gouveia, M; Borges, M; Trindade, R; Rikner, K
Fonte: Sociedade Portuguesa de Cardiologia Publicador: Sociedade Portuguesa de Cardiologia
Tipo: Artigo de Revista Científica
Publicado em //2015 ENG
Relevância na Pesquisa
38.05%
INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

A Potential Mechanism of High-Dose Ticagrelor in Modulating Platelet Activity and Atherosclerosis Mediated by Thymic Stromal Lymphopoietin Receptor

Mao, Yi; Peng, Yudong; Zeng, Qiutang; Cheng, Longxian; Wang, Boyuan; Mao, Xiaobo; Meng, Kai; Liu, Yuzhou; Lian, Yitian; Li, Dazhu
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 30/10/2015 EN
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28.1%
Abnormal expression of thymic stromal lymphopoietin (TSLP) and its receptor (TSLPR) was found in patients with acute coronary syndrome. Ticagrelor, an oral platelet ADP P2Y12 receptor antagonist, is widely used in these patients. The aim of this study was to verify whether different doses of ticagrelor regulated plaque progression and platelet activity by modulating TSLP/TSLPR. Seventy-five ApoE-/- mice were randomly divided into five groups: (1) high-cholesterol diet (HCD, n = 15); (2) HCD plus ticagrelor 25 mg/kg/d (T1, n = 15); (3) HCD plus ticagrelor 50 mg/kg/d (T2, n = 15); (4) HCD plus ticagrelor 100 mg/kg/d (T3, n = 15); and (5) a normal diet group (ND, n = 15). At day 0 and at week 16, blood lipids and serum TSLP levels, expression of TSLPR, CD62, and CD63, platelet aggregation, platelet ATP release, PI3K/Akt signaling pathway, and plaque morphology were assessed. HCD increased TSLPR expression and atherosclerosis progression but high-dose ticagrelor (100 mg/kg) moderated this trend. TSLPR was positively correlated with Akt1, platelet aggregation, corrected plaque area, and vulnerability index in the T3 group (P<0.01). In conclusion, low-dose ticagrelor only inhibited platelet activity. Besides this inhibition, high-dose ticagrelor modulated platelet activity and atherosclerosis mediated by TSLPR...

Ticagrelor en el síndrome coronario agudo: Explicando lo inexplicable

Criniti,Juan Martín; Izcovich,Ariel; Popoff,Federico; Ruiz,Juan Ignacio; Catalano,Hugo N.
Fonte: Medicina (Buenos Aires) Publicador: Medicina (Buenos Aires)
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2014 ES
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En el estudio PLATO se evaluó la utilidad del agregado de ticagrelor, en lugar de clopidogrel, a aspirina en pacientes con síndrome coronario agudo, mostrando resultados sorprendentemente positivos que llevaron a que la droga sea aceptada por las agencias regulatorias y las sociedades especializadas de todo el mundo. Sin embargo, el análisis crítico de los informes presentados por el patrocinador reveló la existencia de distintos aspectos difíciles de explicar y que ponen en tela de juicio la veracidad de sus resultados. La pérdida de seguimiento no explicada, la tasa de mortalidad y los beneficios excesivos no comparables con estudios previos, y la inconsistencia de hallazgos de acuerdo al país, al ente adjudicador de eventos y al comité de monitoreo, son algunos de los puntos más controvertidos. La mayoría de las críticas a este artículo se basan en información que no se desprende del texto del estudio publicado. Esto supone un desafío al análisis crítico de la literatura y genera dudas sobre hasta qué punto el conflicto de interés económico influenció el desarrollo del estudio y la comunicación de sus resultados y, probablemente, la aceptación de la droga para su uso comercial.

Coste-efectividad a largo plazo de ticagrelor frente a clopidogrel en síndrome coronario agudo en España

Molina-Cuadrado,E.; Mateo-Carrasco,H.; Nieto-Guindo,P.; Rodríguez-Gómez,P.
Fonte: Farmacia Hospitalaria Publicador: Farmacia Hospitalaria
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/08/2014 SPA
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Objetivo: Evaluar la relación coste-efectividad de ticagrelor frente a clopidogrel en el tratamiento del síndrome coronario agudo en España. Métodos: Para el cálculo de la tasa de eventos y la calidad de vida relacionada con la salud para ticagrelor y clopidogrel durante los doce primeros meses se utilizaron los datos del estudio PLATO, mientras que los costes se obtuvieron de fuentes españolas. La supervivencia ajustada por calidad de vida y los costes se estimaron en función de que los pacientes no sufrieran ningún evento trombótico (infarto de miocardio o ictus) o éste fuese no mortal. El coste a lo largo de toda la vida, los años de vida ganados y la supervivencia por calidad de vida se estimaron para ambos brazos de tratamiento. Los ratios de coste-efectividad incremental se presentaron desde la perspectiva del sistema sanitario español en 2013, empleando una estrategia de macrocostes basada en la bibliografía publicada y utilizando las tablas de supervivencia de la población española. Resultados: El tratamiento con ticagrelor se asoció con un coste incremental de 1.228 € anuales, un aumento de 0,1652 años de vida ganados y 0,1365 años de vida ajustados por calidad comparado con clopidogrel. Se obtuvo un coste por año de vida ajustado por calidad de 8.997€ y un coste por año de vida ganado de 7.435 €. El análisis de sensibilidad mostró resultados consistentes. Conclusiones: El tratamiento durante 12 meses del síndrome coronario agudo con ticagrelor se asoció a un coste por año de vida ajustado por calidad por debajo de los límites de coste-efectividad generalmente aceptados en España.