Marc P Bonaca1, Deepak L Bhatt2, Robert F Storey3, Ph Gabriel Steg4, Marc Cohen5, Julia Kuder2, Erica Goodrich2, José C Nicolau6, Alexander Parkhomenko7, José López-Sendón8, Mikael Dellborg9, Anthony Dalby10, Jindřich Špinar11, Philip Aylward12, Ramón Corbalán13, Maria Teresa B Abola14, Eva C Jensen15, Peter Held15, Eugene Braunwald2, Marc S Sabatine2. 1. TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts. Electronic address: mbonaca@partners.org. 2. TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts. 3. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom. 4. French Alliance for Cardiovascular Trials, Université Paris-Diderot, Paris, France. 5. Cardiovascular Division, Newark Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York. 6. Heart Institute (InCor)-University of São Paulo Medical School, São Paulo, Brazil. 7. Ukranian Strazhesko Institute of Cardiology, Kiev, Ukraine. 8. Hospital Universitario La Paz, Instituto de Investigación La Paz, Madrid, Spain. 9. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 10. Life Fourways Hospital, Randburg, South Africa. 11. University Hospital, Jihlavska, Brno, Czech Republic. 12. Division of Medicine, Cardiac & Critical Care Services, Flinders Medical Centre, South Australia, Australia. 13. Cardiovascular Division, Pontificia Universidad Católica de Chile, Santiago, Chile. 14. Philippine Heart Center, University of the Philippines College of Medicine, Manila, Philippines. 15. AstraZeneca R&D, Mölndal, Sweden.
Abstract
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 UsingTicagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) toticagrelor 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 UsingTicagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562).
RCT Entities:
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).
Authors: Jacek Kubica; Piotr Adamski; Piotr Niezgoda; Dimitrios Alexopoulos; Jolita Badarienė; Andrzej Budaj; Katarzyna Buszko; Dariusz Dudek; Tomasz Fabiszak; Mariusz Gąsior; Robert Gil; Diana A Gorog; Stefan Grajek; Paul A Gurbel; Marcin Gruchała; Miłosz J Jaguszewski; Stefan James; Young-Hoon Jeong; Bernd Jilma; Jarosław D Kasprzak; Andrzej Kleinrok; Aldona Kubica; Wiktor Kuliczkowski; Jacek Legutko; Maciej Lesiak; Jolanta M Siller-Matula; Klaudiusz Nadolny; Krzysztof Pstrągowski; Salvatore Di Somma; Giuseppe Specchia; Janina Stępińska; Udaya S Tantry; Agnieszka Tycińska; Monica Verdoia; Wojciech Wojakowski; Eliano P Navarese Journal: Cardiol J Date: 2020-10-19 Impact factor: 2.737
Authors: J Antonio Gutierrez; Hillary Mulder; W Schuyler Jones; Frank W Rockhold; Iris Baumgartner; Jeffrey S Berger; Juuso I Blomster; F Gerry R Fowkes; Peter Held; Brian G Katona; Kenneth W Mahaffey; Lars Norgren; William R Hiatt; Manesh R Patel Journal: JAMA Netw Open Date: 2018-11-02