Mukul Sharma1, Robert G Hart1, Eric E Smith2, Jacqueline Bosch1,3, John W Eikelboom1, Stuart J Connolly1, Leanne Dyal1, Kevin W Reeh1, Amparo Casanova1, Rafael Diaz4, Patricio Lopez-Jaramillo5, Georg Ertl6, Stefan Störk6, Gilles R Dagenais7, Eva M Lonn1, Lars Ryden8, Andrew M Tonkin9, John D Varigos9, Deepak L Bhatt10, Kelley R H Branch11,12, Jeffrey L Probstfield12, Jae-Hyung Kim13, Martin O'Donnell14, Dragos Vinereanu15, Keith A A Fox16, Yan Liang17, Lisheng Liu17, Jun Zhu17, Nana Pogosova18, Aldo P Maggioni19, Alvaro Avezum20, Leopoldo S Piegas21, Katalin Keltai22, Matyas Keltai22, Scott D Berkowitz23, Salim Yusuf1. 1. Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, ON, Canada (M.S., R.G.H., J.B., J.W.E., S.J.C., L.D., K.W.R., A.C., E.M.L., S.Y.). 2. Hotchkiss Brain Institute, University of Calgary, AB, Canada (E.E.S.). 3. School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada (J.B.). 4. Estudios Clinicos Latino America and Instituto Cardiovascular de Rosario, Argentina (R.D.). 5. Research Institute, FOSCAL-Bucaramanga, Colombia (P.L.-J.). 6. Comprehensive Heart Failure Center, University and University Hospital, Würzburg, Germany (G.E., S.S.). 7. Institut Universitaire de Cardiologie et Pneumologie de Quebec, Quebec City, Canada (G.R.D.). 8. Karolinska Institutet, Stockholm, Sweden (L.R.). 9. Monash University, Melbourne, Australia (A.M.T., J.D.V.). 10. Brigham and Women's Hospital Heart and Vascular Center, Harvard, Medical School, Boston, MA (D.L.B.). 11. University of Washington Medical Centre, Seattle (K.R.H.B.). 12. University of Washington, Seattle (K.R.H.B., J.L.P.). 13. The Catholic University of Korea, Seoul, Korea (J.-H.K.). 14. National University of Ireland Galway, Galway, Ireland (M.O.). 15. University of Medicine and Pharmacology Carol Davila University and Emergency Hospital, Bucharest, Romania (D.V.). 16. Centre for Cardiovascular Science, University of Edinburgh, Scotland, United Kingdom (K.A.A.F.). 17. FuWai Hospital, Beijing, China (Y.L., L.L., J.Z.). 18. National Research Centre for Preventative Medicine, Moscow, Russia (N.P.). 19. ANMCO Research Center, Florence, Italy (A.P.M.). 20. Hospital Alemão Oswaldo Cruz, Sao Paulo, Brazil (A.A.). 21. University of Sao Paulo, Sao Paulo, Brazil (L.S.P.). 22. Semmelweis University, Budapest, Hungary (K.K., M.K.). 23. Bayer AG, Leverkusen, Germany (S.D.B.).
Abstract
BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.
BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.
Entities:
Keywords:
aspirin; cognition; infarction; rivaroxaban; white matter
Authors: Joseph Kwan; Melanie Hafdi; Lorraine L W Chiang; Phyo K Myint; Li Siang Wong; Terry J Quinn Journal: Cochrane Database Syst Rev Date: 2022-07-14
Authors: Mukul Sharma; Eric E Smith; Lesly A Pearce; Kanjana S Perera; Scott E Kasner; Byung-Woo Yoon; Sebastian F Ameriso; Josep Puig; Dorte Damgaard; Jochen B Fiebach; Keith W Muir; Roland C Veltkamp; Danilo S Toni; Nikolay Shamalov; Rubens J Gagliardi; Robert Mikulik; Stefan T Engelter; Daniel Bereczki; Martin J O'Donnell; Feryal Saad; Ashkan Shoamanesh; Scott D Berkowitz; Hardi Mundl; Robert G Hart Journal: Int J Stroke Date: 2021-11-18 Impact factor: 6.948