Deepak L Bhatt1, Marc P Bonaca2, Sameer Bansilal3, Dominick J Angiolillo4, Marc Cohen5, Robert F Storey6, Kyungah Im2, Sabina A Murphy2, Peter Held7, Eugene Braunwald2, Marc S Sabatine2, Ph Gabriel Steg8. 1. TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts. Electronic address: dlbhattmd@post.harvard.edu. 2. TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts. 3. Icahn School of Medicine at Mount Sinai, New York, New York. 4. University of Florida, Jacksonville, Florida. 5. Cardiovascular Division, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark, New Jersey. 6. University of Sheffield, Sheffield, United Kingdom. 7. AstraZeneca R&D, Mölndal, Sweden. 8. Département Hospitalo-Universitaire-Fibrosis, Inflammation, REmodelling, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris-Diderot, Sorbonne-Paris Cité, and the French Alliance for Cardiovascular Clinical Trials, an F-CRIN network, INSERM U-1148, Paris, France.
Abstract
BACKGROUND:Patients with diabetes appear to be at elevated risk of atherothrombotic events. OBJECTIVES: The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI). METHODS: We examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack UsingTicagrelor Compared to Placebo on a Background of Aspirin-ThrombolysisIn Myocardial Infarction 54), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding. RESULTS: The relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004). CONCLUSIONS: In patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack UsingTicagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
RCT Entities:
BACKGROUND:Patients with diabetes appear to be at elevated risk of atherothrombotic events. OBJECTIVES: The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI). METHODS: We examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) 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), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding. RESULTS: The relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004). CONCLUSIONS: In patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; 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