E Hope Weissler1, W Schuyler Jones2, Ileana Desormais3, Sebastian Debus4, Lucia Mazzolai5, Christine Espinola-Klein6, Sigrid Nikol7, Mark Nehler8, Henrik Sillesen9, Victor Aboyans10, Manesh R Patel11. 1. Division of Vascular and Endovascular Surgery, Duke University Health System, Durham, NC, USA. 2. Division of Cardiology, Department of Medicine Duke University Health System, USA; Duke Clinical Research Institute, Durham, NC, USA. Electronic address: schuyler.jones@dm.duke.edu. 3. INSERM U1094, University Limoges, CHU Limoges, IRD, U1094, Tropical Neuroepidemiology, Institute of Epidemiology and Tropical Neurology, GEIST, Department of Vascular Surgery and Angiology, Dupuytren University Hospital, Limoges, France. 4. Department of Vascular Medicine (Vascular Surgery-Angiology-Endovascular Therapy), University Heart & Vascular Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 5. Angiology Department, Lausanne University Hospital (CHUV), Lausanne, Switzerland. 6. Center for Cardiology - Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. 7. Clinical and Interventional Angiology, Asklepios Klinik St. Georg, Hamburg, Germany. 8. Department of Surgery UC Denver and CPC Research, Aurora, CO, USA. 9. Department of Vascular Surgery, Rigshospitalet, Copenhagen and Institute of Clinical Medicine, University of Copenhagen, Denmark. 10. INSERM UMR 1094, Tropical Neuroepidemiology, Department of Cardiology, Dupuytren University Hospital, Limoges, France. 11. Division of Cardiology, Department of Medicine Duke University Health System, USA; Duke Clinical Research Institute, Durham, NC, USA.
Abstract
BACKGROUND AND AIMS: Polyvascular disease (PVD) affects approximately 20% of patients with atherosclerosis and is a strong independent risk factor for ischemic outcomes. However, guidelines do not address screening or treatment for PVD, and there have been no PVD-specific trials. We reviewed subgroup analyses of large randomized controlled trials of more intense antithrombotic therapy to determine whether increased intensity of therapy improved ischemic outcomes in patients with PVD. METHODS: MEDLINE, MEDLINE in-Process, EMBASE, and the Cochrane Library were queried for randomized controlled trials larger than 5000 patients evaluating secondary prevention therapies in patients with coronary artery disease or lower extremity peripheral artery disease. RESULTS: Thirteen trials were included ranging in size from 7243 to 27,395 patients. In 9 trials (CHARISMA, TRA 2°P-TIMI 50, PEGASUS-TIMI 54, VOYAGER PAD, TRACER, EUCLID, TRILOGY ACS, PLATO, and COMPASS), patients in the PVD subgroup treated with increased-intensity antithrombotic therapy had similar or greater relative risk reductions for ischemic events in comparison with the general trial cohorts. In four trials (DAPT, THEMIS, APPRAISE-2, and ATLAS ACS 2 TIMI 51), the PVD subgroup had an increased hazard of ischemic events with increased-intensity therapy compared with the general trial cohorts. CONCLUSIONS: More intense antithrombotic therapy in patients with PVD was associated with a similar relative risk reduction for ischemic events compared with patients without PVD. Therefore, patients with PVD benefit from a larger absolute risk reduction because of their higher baseline risk. Future trials in patients with atherosclerotic cardiovascular disease should intentionally include PVD patients to adequately assess treatment options for this under-studied, under-treated population.
BACKGROUND AND AIMS: Polyvascular disease (PVD) affects approximately 20% of patients with atherosclerosis and is a strong independent risk factor for ischemic outcomes. However, guidelines do not address screening or treatment for PVD, and there have been no PVD-specific trials. We reviewed subgroup analyses of large randomized controlled trials of more intense antithrombotic therapy to determine whether increased intensity of therapy improved ischemic outcomes in patients with PVD. METHODS: MEDLINE, MEDLINE in-Process, EMBASE, and the Cochrane Library were queried for randomized controlled trials larger than 5000 patients evaluating secondary prevention therapies in patients with coronary artery disease or lower extremity peripheral artery disease. RESULTS: Thirteen trials were included ranging in size from 7243 to 27,395 patients. In 9 trials (CHARISMA, TRA 2°P-TIMI 50, PEGASUS-TIMI 54, VOYAGER PAD, TRACER, EUCLID, TRILOGY ACS, PLATO, and COMPASS), patients in the PVD subgroup treated with increased-intensity antithrombotic therapy had similar or greater relative risk reductions for ischemic events in comparison with the general trial cohorts. In four trials (DAPT, THEMIS, APPRAISE-2, and ATLAS ACS 2 TIMI 51), the PVD subgroup had an increased hazard of ischemic events with increased-intensity therapy compared with the general trial cohorts. CONCLUSIONS: More intense antithrombotic therapy in patients with PVD was associated with a similar relative risk reduction for ischemic events compared with patients without PVD. Therefore, patients with PVD benefit from a larger absolute risk reduction because of their higher baseline risk. Future trials in patients with atherosclerotic cardiovascular disease should intentionally include PVD patients to adequately assess treatment options for this under-studied, under-treated population.