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Robert F Storey - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety with Ticagrelor in patients with prior myocardial infarction in the approved european label insights from pegasus timi 54
    European Heart Journal - Cardiovascular Pharmacotherapy, 2019
    Co-Authors: Mikael Dellborg, Robert F Storey, Marc P Bonaca, Deepak L Bhatt, Marc Cohen, Ton Oude Ophuis, Gabriel P Steg, Andrezej Budaj, Christian W Hamm, Jindrich Spinar
    Abstract:

    Aims In PEGASUS-TIMI 54, Ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15–16% in stable patients with a prior myocardial infarction (MI) 1–3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment. Methods and results Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to Ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan–Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the Ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70–0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67–0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the Ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65–3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68–2.01; P = 0.58). Conclusion In PEGASUS-TIMI 54, treatment with Ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term Ticagrelor 60 mg in this population. Clinical trial registration http://www.clinicaltrials.gov NCT01225562

  • Ticagrelor for secondary prevention of atherothrombotic events in patients with multivessel coronary disease
    Journal of the American College of Cardiology, 2018
    Co-Authors: Sameer Bansilal, Robert F Storey, Dominick J Angiolillo, Marc P Bonaca, Deepak L Bhatt, Sabina A Murphy, Jan H Cornel, Ph Gabriel Steg, Robert Gabor Kiss, Alexander Parkhomenko
    Abstract:

    Abstract Background Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events. Objectives The authors investigated the efficacy and safety of Ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial. Methods Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of Ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months. Results A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HR adj ]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HR adj : 1.49; p = 0.0005). In patients with MVD, Ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p  Conclusions Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term Ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, Ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

  • efficacy and safety of Ticagrelor over time in patients with prior mi in pegasus timi 54
    Journal of the American College of Cardiology, 2017
    Co-Authors: Marc P Bonaca, Robert F Storey, Deepak L Bhatt, Marc Cohen, Giulia Magnani, Ton Oude Ophuis, Gabriel P Steg, Pierre Theroux, Sabina A Murphy, Mikhail Rudah
    Abstract:

    Abstract Background Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time. Objectives The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of Ticagrelor were similar early and late after randomization. Methods The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to Ticagrelor 90 mg, Ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3). Results A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of Ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with Ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65). Conclusions Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose Ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

  • cost effectiveness of long term Ticagrelor in patients with prior myocardial infarction results from the pegasus timi 54 trial
    Journal of the American College of Cardiology, 2017
    Co-Authors: Elizabeth A Magnuson, Robert F Storey, Philippe Gabriel Steg, Kaijun Wang, Katherine Vilain, Ali Shafiq, Marc P Bonaca, Deepak L Bhatt, Marc Cohen, Eugene Braunwald
    Abstract:

    Abstract Background In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with Ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. Objectives The authors evaluated cost-effectiveness of Ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. Methods The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, Ticagrelor 60 mg twice daily + low-dose ASA, or Ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration–approved lower-dose Ticagrelor regimen (60 mg twice daily). Results Hospitalization costs were similar for Ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference −$303 to $163; p = 0.54); after inclusion of a daily Ticagrelor 60 mg cost of $10.52, total costs were higher for Ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p  1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age  Conclusions For patients with a history of MI >1 year previously, long-term treatment with Ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562 )

  • relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non st segment elevation acute coronary syndrome in the plato trial
    Clinical Cardiology, 2017
    Co-Authors: Charles V Pollack, Stefan James, Philippe Gabriel Steg, Richard C Becker, Farideh Davoudi, Deborah B Diercks, Soo Teik Lim, Phillip J Schulte, Jindrich Spinar, Robert F Storey
    Abstract:

    Background Guidelines suggest that “upstream” P2Y12 receptor antagonists should be considered in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS). Hypothesis Early use of Ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. Methods In the PLATO trial, 6792 NSTE-ACS patients were randomized to Ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of Ticagrelor vs clopidogrel as a function of “early” (<3h) vs “late” (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. Results Overall, a benefit of Ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between Ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with Ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. Conclusions The benefit of Ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of Ticagrelor.

Otavio Berwanger - One of the best experts on this subject based on the ideXlab platform.

  • Ticagrelor versus clopidogrel in patients with stemi treated with fibrinolysis treat trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Otavio Berwanger, Diogo D F Moia, Francisco Antonio Helfenstein Fonseca, Oleg Averkov, Shaun G Goodman, Renato D Lopes, Stephen J Nicholls, Lixin Jiang, Alexander Parkhomenko, Carlos Tajer
    Abstract:

    Abstract Background The efficacy of Ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. Objectives The purpose of this study was to evaluate the efficacy of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Methods This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age  Results The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving Ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with Ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the Ticagrelor and clopidogrel groups. Conclusion Among patients age

  • Ticagrelor versus clopidogrel in patients with stemi treated with fibrinolytic therapy treat trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Otavio Berwanger, Diogo D F Moia, Francisco Antonio Helfenstein Fonseca, Shaun G Goodman, Renato D Lopes, Stephen J Nicholls, Lixin Jiang, Anzhelika Parkhomenko
    Abstract:

    Abstract Background The efficacy of Ticagrelor in the long-term post ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. Objectives To evaluate the efficacy of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Methods We conducted an international, multicenter, randomized, open-label with blinded endpoint adjudication trial that enrolled 3,799 patients (age Results The combined outcome of cardiovascular mortality, myocardial infarction or stroke occurred in 129 of 1,913 patients (6.7%) receiving Ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio of 0.93; 95% CI, 0.73 to 1.18; P=0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with Ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio of 0.88; 95% CI, 0.71 to 1.09; P=0.25). The rates of major, fatal, and intracranial bleeding were similar between the Ticagrelor and clopidogrel groups. Conclusions Among patients aged under 75 years with STEMI, administration of Ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel.

  • Ticagrelor versus clopidogrel in patients with stemi treated with fibrinolytic therapy treat trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Otavio Berwanger, Diogo D F Moia, Francisco Antonio Helfenstein Fonseca, Shaun G Goodman, Renato D Lopes, Stephen J Nicholls, Lixin Jiang, Alexander Parkhomenko
    Abstract:

    Abstract Background The efficacy of Ticagrelor in the long-term post ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. Objectives To evaluate the efficacy of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Methods We conducted an international, multicenter, randomized, open-label with blinded endpoint adjudication trial that enrolled 3,799 patients (age Results The combined outcome of cardiovascular mortality, myocardial infarction or stroke occurred in 129 of 1,913 patients (6.7%) receiving Ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio of 0.93; 95% CI, 0.73 to 1.18; P=0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with Ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio of 0.88; 95% CI, 0.71 to 1.09; P=0.25). The rates of major, fatal, and intracranial bleeding were similar between the Ticagrelor and clopidogrel groups. Conclusions Among patients aged under 75 years with STEMI, administration of Ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel.

  • Ticagrelor versus clopidogrel after fibrinolytic therapy in patients with st elevation myocardial infarction rationale and design of the Ticagrelor in patients with st elevation myocardial infarction treated with thrombolysis treat trial
    American Heart Journal, 2018
    Co-Authors: Otavio Berwanger, Oleg Averkov, Carlos Tajer, Shaun G Goodman, Jose C. Nicolau, Stephen J Nicholls, Lixin Jiang, Alexander Parkhomenko, Antonio Carlos Campos De Carvalho, German Malaga
    Abstract:

    Abstract Background The safety and efficacy of Ticagrelor in patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain. Objectives The primary objective of the Ticagrelor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short-term safety of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of Ticagrelor compared with clopidogrel at 12-months. Design The TREAT trial is a multicenter, randomized, phase III, Prospective randomized open blinded end-point (PROBE) study that enrolled 3,799 patients in 152 sites from 10 countries. Following administration of fibrinolytic therapy patients were randomized to a loading dose of Ticagrelor 180 mg or clopidogrel 300 mg followed by a maintenance dose of Ticagrelor 90 mg twice daily or clopidogrel 75 mg/day for 12-months. The primary outcome is the rate of TIMI major bleeding at 30-days and will be assessed for non-inferiority using an intention-to-treat analysis. Co-treatments include aspirin and anticoagulants. Other evidence based therapies are also recommended. Secondary efficacy outcome include a composite of death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic event. All-cause mortality as well as individual components of the combined efficacy endpoint will also be ascertained. Summary TREAT is an international randomized controlled trial comparing Ticagrelor with clopidogrel in STEMI patients treated with fibrinolytic therapy. The results of this trial will inform clinical practice and international guidelines.

  • Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st elevation myocardial infarction a randomized clinical trial
    JAMA Cardiology, 2018
    Co-Authors: Otavio Berwanger, Oleg Averkov, Carlos Tajer, Shaun G Goodman, Antonio Carlos Carvalho, Anzhelika Parkhomenko, Jose C. Nicolau, Stephen J Nicholls, Lixin Jiang, German Malaga
    Abstract:

    Importance The bleeding safety of Ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain. Objective To evaluate the short-term safety of Ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. Design, Setting and Participants We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. Interventions Patients were randomized to Ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. Main Outcomes and Measures The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days. Results The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving Ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, −0.49% to 0.58%; P P  = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P  = .67) and intracranial bleeding (0.42% vs 0.37%; P  = .82) were similar between the Ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with Ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with Ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P  = .57). Conclusions and Relevance In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of Ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days. Trial Registration clinicaltrials.gov Identifier:NCT02298088

Shaun G Goodman - One of the best experts on this subject based on the ideXlab platform.

  • Ticagrelor versus clopidogrel in patients with stemi treated with fibrinolysis treat trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Otavio Berwanger, Diogo D F Moia, Francisco Antonio Helfenstein Fonseca, Oleg Averkov, Shaun G Goodman, Renato D Lopes, Stephen J Nicholls, Lixin Jiang, Alexander Parkhomenko, Carlos Tajer
    Abstract:

    Abstract Background The efficacy of Ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. Objectives The purpose of this study was to evaluate the efficacy of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Methods This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age  Results The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving Ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with Ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the Ticagrelor and clopidogrel groups. Conclusion Among patients age

  • Ticagrelor versus clopidogrel in patients with stemi treated with fibrinolytic therapy treat trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Otavio Berwanger, Diogo D F Moia, Francisco Antonio Helfenstein Fonseca, Shaun G Goodman, Renato D Lopes, Stephen J Nicholls, Lixin Jiang, Anzhelika Parkhomenko
    Abstract:

    Abstract Background The efficacy of Ticagrelor in the long-term post ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. Objectives To evaluate the efficacy of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Methods We conducted an international, multicenter, randomized, open-label with blinded endpoint adjudication trial that enrolled 3,799 patients (age Results The combined outcome of cardiovascular mortality, myocardial infarction or stroke occurred in 129 of 1,913 patients (6.7%) receiving Ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio of 0.93; 95% CI, 0.73 to 1.18; P=0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with Ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio of 0.88; 95% CI, 0.71 to 1.09; P=0.25). The rates of major, fatal, and intracranial bleeding were similar between the Ticagrelor and clopidogrel groups. Conclusions Among patients aged under 75 years with STEMI, administration of Ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel.

  • Ticagrelor versus clopidogrel in patients with stemi treated with fibrinolytic therapy treat trial
    Journal of the American College of Cardiology, 2019
    Co-Authors: Otavio Berwanger, Diogo D F Moia, Francisco Antonio Helfenstein Fonseca, Shaun G Goodman, Renato D Lopes, Stephen J Nicholls, Lixin Jiang, Alexander Parkhomenko
    Abstract:

    Abstract Background The efficacy of Ticagrelor in the long-term post ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain. Objectives To evaluate the efficacy of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Methods We conducted an international, multicenter, randomized, open-label with blinded endpoint adjudication trial that enrolled 3,799 patients (age Results The combined outcome of cardiovascular mortality, myocardial infarction or stroke occurred in 129 of 1,913 patients (6.7%) receiving Ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio of 0.93; 95% CI, 0.73 to 1.18; P=0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with Ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio of 0.88; 95% CI, 0.71 to 1.09; P=0.25). The rates of major, fatal, and intracranial bleeding were similar between the Ticagrelor and clopidogrel groups. Conclusions Among patients aged under 75 years with STEMI, administration of Ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel.

  • Ticagrelor versus clopidogrel after fibrinolytic therapy in patients with st elevation myocardial infarction rationale and design of the Ticagrelor in patients with st elevation myocardial infarction treated with thrombolysis treat trial
    American Heart Journal, 2018
    Co-Authors: Otavio Berwanger, Oleg Averkov, Carlos Tajer, Shaun G Goodman, Jose C. Nicolau, Stephen J Nicholls, Lixin Jiang, Alexander Parkhomenko, Antonio Carlos Campos De Carvalho, German Malaga
    Abstract:

    Abstract Background The safety and efficacy of Ticagrelor in patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain. Objectives The primary objective of the Ticagrelor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short-term safety of Ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of Ticagrelor compared with clopidogrel at 12-months. Design The TREAT trial is a multicenter, randomized, phase III, Prospective randomized open blinded end-point (PROBE) study that enrolled 3,799 patients in 152 sites from 10 countries. Following administration of fibrinolytic therapy patients were randomized to a loading dose of Ticagrelor 180 mg or clopidogrel 300 mg followed by a maintenance dose of Ticagrelor 90 mg twice daily or clopidogrel 75 mg/day for 12-months. The primary outcome is the rate of TIMI major bleeding at 30-days and will be assessed for non-inferiority using an intention-to-treat analysis. Co-treatments include aspirin and anticoagulants. Other evidence based therapies are also recommended. Secondary efficacy outcome include a composite of death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic event. All-cause mortality as well as individual components of the combined efficacy endpoint will also be ascertained. Summary TREAT is an international randomized controlled trial comparing Ticagrelor with clopidogrel in STEMI patients treated with fibrinolytic therapy. The results of this trial will inform clinical practice and international guidelines.

  • Ticagrelor vs clopidogrel after fibrinolytic therapy in patients with st elevation myocardial infarction a randomized clinical trial
    JAMA Cardiology, 2018
    Co-Authors: Otavio Berwanger, Oleg Averkov, Carlos Tajer, Shaun G Goodman, Antonio Carlos Carvalho, Anzhelika Parkhomenko, Jose C. Nicolau, Stephen J Nicholls, Lixin Jiang, German Malaga
    Abstract:

    Importance The bleeding safety of Ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain. Objective To evaluate the short-term safety of Ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. Design, Setting and Participants We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. Interventions Patients were randomized to Ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. Main Outcomes and Measures The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days. Results The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving Ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, −0.49% to 0.58%; P P  = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P  = .67) and intracranial bleeding (0.42% vs 0.37%; P  = .82) were similar between the Ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with Ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with Ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P  = .57). Conclusions and Relevance In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of Ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days. Trial Registration clinicaltrials.gov Identifier:NCT02298088

Deepak L Bhatt - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety with Ticagrelor in patients with prior myocardial infarction in the approved european label insights from pegasus timi 54
    European Heart Journal - Cardiovascular Pharmacotherapy, 2019
    Co-Authors: Mikael Dellborg, Robert F Storey, Marc P Bonaca, Deepak L Bhatt, Marc Cohen, Ton Oude Ophuis, Gabriel P Steg, Andrezej Budaj, Christian W Hamm, Jindrich Spinar
    Abstract:

    Aims In PEGASUS-TIMI 54, Ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15–16% in stable patients with a prior myocardial infarction (MI) 1–3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment. Methods and results Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to Ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan–Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the Ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70–0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67–0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the Ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65–3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68–2.01; P = 0.58). Conclusion In PEGASUS-TIMI 54, treatment with Ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term Ticagrelor 60 mg in this population. Clinical trial registration http://www.clinicaltrials.gov NCT01225562

  • Ticagrelor for secondary prevention of atherothrombotic events in patients with multivessel coronary disease
    Journal of the American College of Cardiology, 2018
    Co-Authors: Sameer Bansilal, Robert F Storey, Dominick J Angiolillo, Marc P Bonaca, Deepak L Bhatt, Sabina A Murphy, Jan H Cornel, Ph Gabriel Steg, Robert Gabor Kiss, Alexander Parkhomenko
    Abstract:

    Abstract Background Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events. Objectives The authors investigated the efficacy and safety of Ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial. Methods Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of Ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months. Results A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HR adj ]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HR adj : 1.49; p = 0.0005). In patients with MVD, Ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p  Conclusions Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term Ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, Ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

  • efficacy and safety of Ticagrelor over time in patients with prior mi in pegasus timi 54
    Journal of the American College of Cardiology, 2017
    Co-Authors: Marc P Bonaca, Robert F Storey, Deepak L Bhatt, Marc Cohen, Giulia Magnani, Ton Oude Ophuis, Gabriel P Steg, Pierre Theroux, Sabina A Murphy, Mikhail Rudah
    Abstract:

    Abstract Background Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time. Objectives The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of Ticagrelor were similar early and late after randomization. Methods The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to Ticagrelor 90 mg, Ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3). Results A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of Ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with Ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65). Conclusions Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose Ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

  • cost effectiveness of long term Ticagrelor in patients with prior myocardial infarction results from the pegasus timi 54 trial
    Journal of the American College of Cardiology, 2017
    Co-Authors: Elizabeth A Magnuson, Robert F Storey, Philippe Gabriel Steg, Kaijun Wang, Katherine Vilain, Ali Shafiq, Marc P Bonaca, Deepak L Bhatt, Marc Cohen, Eugene Braunwald
    Abstract:

    Abstract Background In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with Ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. Objectives The authors evaluated cost-effectiveness of Ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. Methods The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, Ticagrelor 60 mg twice daily + low-dose ASA, or Ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration–approved lower-dose Ticagrelor regimen (60 mg twice daily). Results Hospitalization costs were similar for Ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference −$303 to $163; p = 0.54); after inclusion of a daily Ticagrelor 60 mg cost of $10.52, total costs were higher for Ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p  1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age  Conclusions For patients with a history of MI >1 year previously, long-term treatment with Ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562 )

  • prevention of stroke with Ticagrelor in patients with prior myocardial infarction insights from pegasus timi 54 prevention of cardiovascular events in patients with prior heart attack using Ticagrelor compared to placebo on a background of aspirin thrombolysis in myocardial infarction 54
    Circulation, 2016
    Co-Authors: Marc P Bonaca, Robert F Storey, Deepak L Bhatt, Marc Cohen, Ton Oude Ophuis, Gabriel P Steg, Shinya Goto, Erica L Goodrich, Laura Mauri, Michail Ruda
    Abstract:

    BACKGROUND: In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), Ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of Ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of Ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. METHODS: Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. RESULTS: Of 14 112 patients randomly assigned to placebo or Ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on Ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). CONCLUSIONS: High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of Ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke.

Philippe Gabriel Steg - One of the best experts on this subject based on the ideXlab platform.

  • cost effectiveness of long term Ticagrelor in patients with prior myocardial infarction results from the pegasus timi 54 trial
    Journal of the American College of Cardiology, 2017
    Co-Authors: Elizabeth A Magnuson, Robert F Storey, Philippe Gabriel Steg, Kaijun Wang, Katherine Vilain, Ali Shafiq, Marc P Bonaca, Deepak L Bhatt, Marc Cohen, Eugene Braunwald
    Abstract:

    Abstract Background In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with Ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. Objectives The authors evaluated cost-effectiveness of Ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. Methods The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, Ticagrelor 60 mg twice daily + low-dose ASA, or Ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration–approved lower-dose Ticagrelor regimen (60 mg twice daily). Results Hospitalization costs were similar for Ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference −$303 to $163; p = 0.54); after inclusion of a daily Ticagrelor 60 mg cost of $10.52, total costs were higher for Ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p  1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age  Conclusions For patients with a history of MI >1 year previously, long-term treatment with Ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562 )

  • relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non st segment elevation acute coronary syndrome in the plato trial
    Clinical Cardiology, 2017
    Co-Authors: Charles V Pollack, Stefan James, Philippe Gabriel Steg, Richard C Becker, Farideh Davoudi, Deborah B Diercks, Soo Teik Lim, Phillip J Schulte, Jindrich Spinar, Robert F Storey
    Abstract:

    Background Guidelines suggest that “upstream” P2Y12 receptor antagonists should be considered in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS). Hypothesis Early use of Ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. Methods In the PLATO trial, 6792 NSTE-ACS patients were randomized to Ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of Ticagrelor vs clopidogrel as a function of “early” (<3h) vs “late” (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. Results Overall, a benefit of Ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between Ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with Ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. Conclusions The benefit of Ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of Ticagrelor.

  • long term use of Ticagrelor in patients with prior myocardial infarction
    The New England Journal of Medicine, 2015
    Co-Authors: Marc P Bonaca, Robert F Storey, Philippe Gabriel Steg, Deepak L Bhatt, Marc Cohen, Eva C Jensen, Giulia Magnani, Sameer Bansilal, Polly M Fish, Kyungah Im
    Abstract:

    BACKGROUND The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of Ticagrelor, a P2Y 12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context. METHODS We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to Ticagrelor at a dose of 90 mg twice daily, Ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. RESULTS The two Ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan–Meier rates at 3 years of 7.85% in the group that received 90 mg of Ticagrelor twice daily, 7.77% in the group that received 60 mg of Ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of Ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P = 0.008; hazard ratio for 60 mg of Ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P = 0.004). Rates of TIMI major bleeding were higher with Ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively. CONCLUSIONS In patients with a myocardial infarction more than 1 year previously, treatment with Ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.)

  • Ticagrelor effects on myocardial infarction and the impact of event adjudication in the plato platelet inhibition and patient outcomes trial
    Journal of the American College of Cardiology, 2014
    Co-Authors: Kenneth W Mahaffey, Claes Held, Daniel Wojdyla, Stefan James, Hugo A Katus, Steen Husted, Philippe Gabriel Steg, Christopher P Cannon, Richard C Becker, Robert F Storey
    Abstract:

    Objectives This study sought to report the treatment effect of Ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background In PLATO, Ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). Methods A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, excluded silent MI. Results Overall, 1,299 (610 Ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 Ticagrelor, 593 clopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 Ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% Ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with Ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned Ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). Conclusions In patients with ACS, Ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872 )

  • Ticagrelor versus clopidogrel in patients with st elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention a platelet inhibition and patient outcomes plato trial subgroup analysis
    Circulation, 2010
    Co-Authors: Philippe Gabriel Steg, Stefan James, Steen Husted, Christopher P Cannon, Richard C Becker, Hakan Emanuelsson, Diego Ardissino, Robert A Harrington, Ariel Finkelstein, Hugo Katus
    Abstract:

    Background— Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention. Methods and Result— Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared Ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either Ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with Ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P =0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P =0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P =0.03), total mortality (HR, 0.82; P =0.05), and definite stent thrombosis (HR, 0.66; P =0.03). The risk of stroke, low in both groups, was higher with Ticagrelor (1.7% versus 1.0%; HR,1.63; 95% confidence interval, 1.07 to 2.48; P =0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P =0.76). Conclusion— In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of Ticagrelor were consistent with those observed in the overall PLATO trial. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00391872.