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Článek online

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)

Bonaca, Marc P
Autor Bonaca, Marc P From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.). mbonaca@partners.org
Goto, Shinya
Autor Goto, Shinya From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Bhatt, Deepak L
Autor Bhatt, Deepak L From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Steg, P Gabriel
Autor Steg, P Gabriel From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Storey, Robert F
Autor Storey, Robert F From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Cohen, Marc
Autor Cohen, Marc From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Goodrich, Erica
Autor Goodrich, Erica From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Mauri, Laura
Autor Mauri, Laura From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Ophuis, Ton Oude
Autor Ophuis, Ton Oude From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)
Ruda, Mikhail
Autor Ruda, Mikhail From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.) Tokai University School of Medicine Institute of Medical Science, Isehara, Japan (S.G.) FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.) University of Sheffield, United Kingdom (R.F.S.) Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.) Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.) CWZ Hospital, Nijmegen, The Netherlands (T.O.O.) Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.) Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.) Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.) Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.) Life Fourways Hospital, Randburg, South Africa (A.J.D.) and AstraZeneca, Mölndal, Sweden (E.J., P.H.)

Circulation (New York, N.Y.). 2016 ; 134 (12) : 861-71. [pub] 20160830

Circulation (New York)
ISSN 1524-4539
Medvik
Zdroj

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. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.

Článek online

Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease

Journal of the American College of Cardiology. 2016 ; 67 (23) : 2719-28. [pub] 20160401

J. Am. Coll. Cardiol.
ISSN 1558-3597
Medvik
Zdroj

BACKGROUND: Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). OBJECTIVES: This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. METHODS: 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) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. RESULTS: A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). CONCLUSIONS: Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562).

Článek

Long-term Tolerability of Ticagrelor for the Secondary Prevention of Major Adverse Cardiovascular Events: A Secondary Analysis of the PEGASUS-TIMI 54 Trial

JAMA cardiology. 2016 ; 1 (4) : 425-32.

JAMA Cardiol
ISSN 2380-6591
Medvik
Zdroj

IMPORTANCE: In the PEGASUS-TIMI 54 trial, treatment with ticagrelor reduced the incidence of cardiovascular death, myocardial infarction, or stroke by 15% to 16% among stable patients compared with placebo. However, more patients prematurely discontinued treatment with ticagrelor than with placebo. OBJECTIVE: To investigate the reasons and timing of discontinuation of treatment with ticagrelor among stable patients prior myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: In the PEGASUS-TIMI 54 trial, 21 162 stable outpatients with prior myocardial infarction were randomly assigned to 90 mg of ticagrelor twice daily, 60 mg of ticagrelor twice daily, or placebo, with all of the patients receiving a low dose of aspirin. These participants were followed up for a median of 33 months (study start date: October 2010; completion date: December 2014). Discontinuation of treatment was evaluated by treatment arm, cause, and timing. This analysis was initiated in May 2015. MAIN OUTCOME AND MEASURE: Discontinuation of treatment. RESULTS: Over 33 months, 32%, 29%, and 21% of patients receiving 90 mg of ticagrelor, 60 mg of ticagrelor, and placebo, respectively, discontinued treatment (P < .001). Discontinuation of treatment due to an adverse event occurred in 19%, 16%, and 9% of patients, respectively (P < .001). The most frequent adverse events leading to discontinuation of treatment were bleeding (with Kaplan-Meier event rates of 7.8%, 6.2%, and 1.5% of patients, respectively; P < .001) and dyspnea (6.5%, 4.6%, and 0.8% of patients, respectively; P < .001). Eighty-six percent of bleeding events that led to the discontinuation of treatment with ticagrelor were nonmajor, and 86% of adverse events due to dyspnea that led to discontinuation of treatment with ticagrelor were mild or moderate in severity. The discontinuation rates are annualized for patients who received 90 mg of ticagrelor twice daily (hazard ratio [HR], 2.00 [95% CI, 1.84-2.16] for the first year; HR, 1.12 [95% CI, 1.00-1.26] for the second and third years) and patients who received 60 mg of ticagrelor twice daily (HR, 1.59 [95% CI, 1.46-1.73] for the first year; HR, 1.18 [95% CI, 1.06-1.32] for the second and third years) compared with patients who received placebo. CONCLUSIONS AND RELEVANCE: When initiated among stable patients with prior myocardial infarction, discontinuation of treatment with ticagrelor was driven primarily by nonserious adverse events occurring primarily early after randomization. For patients completing 1 year of treatment, the subsequent discontinuation rate was low. These data demonstrate how adverse events considered "nonserious" by traditional trial criteria may have an effect on quality of life and, thus, may precipitate the discontinuation of treatments and underscore the need for patient education and counseling on the timing and nature of adverse effects with the aim of improving adherence when appropriate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01225562.

MeSH
adenosin škodlivé účinky analogy a deriváty terapeutické užití MeSH
antagonisté purinergních receptorů P2Y MeSH
cévní mozková příhoda prevence a kontrola MeSH
dyspnoe chemicky indukované MeSH
infarkt myokardu prevence a kontrola MeSH
krvácení chemicky indukované MeSH
kvalita života MeSH
lidé MeSH
sekundární prevence * MeSH
ticagrelor MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
randomizované kontrolované studie MeSH

Článek online

Long-term use of ticagrelor in patients with prior myocardial infarction

The New England journal of medicine. 2015 ; 372 (19) : 1791-800.

N Engl J Med
ISSN 1533-4406
Medvik
Zdroj

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 P2Y12 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.).