Sanjit S Jolly1, John A Cairns2, Salim Yusuf3, Brandi Meeks3, Peggy Gao3, Robert G Hart3, Sasko Kedev4, Goran Stankovic5, Raul Moreno6, David Horak7, Saleem Kassam8, Michael J Rokoss3, Raymond C M Leung9, Magdi El-Omar10, Hannu O Romppanen11, Ashraf Alazzoni3, Aiman Alak3, Anthony Fung12, Dimitrios Alexopoulos13, John D Schwalm3, Nicholas Valettas3, Vladimír Džavík14. 1. The Population Health Research Institute, Hamilton Health Sciences, McMaster University, Rm. C3-118, DBCVSRI Building, Hamilton General Hospital, 237 Barton St. East, Hamilton, ON, L8L 2X2, Canada sanjit.jollly@phri.ca. 2. Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 3. The Population Health Research Institute, Hamilton Health Sciences, McMaster University, Rm. C3-118, DBCVSRI Building, Hamilton General Hospital, 237 Barton St. East, Hamilton, ON, L8L 2X2, Canada. 4. University Clinic of Cardiology, Sts. Cyril and Methodius University, Skopje, Macedonia. 5. Clinical Center of Serbia, Department of Cardiology, Medical Faculty, University of Belgrade, Belgrade, Serbia. 6. University Hospital La Paz, Madrid, Spain. 7. Krajská Nemocnice Liberec, Liberec, Czech Republic. 8. Rouge Valley Health System, Toronto, ON, Canada. 9. CK Hui Heart Centre, Edmonton, AB, Canada. 10. Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. 11. Heart Centre, Kuopio University Hospital, Kuopio, Finland. 12. Division of Cardiology, Vancouver General Hospital/University of British Columbia, Vancouver, BC, Canada. 13. Patras University Hospital, Patras, Greece. 14. Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
Abstract
AIMS: TOTAL (N = 10 732), a randomized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction, showed no difference in the primary efficacy outcome but a significant increase in stroke. We sought to understand these findings. METHODS AND RESULTS: A detailed analysis of stroke timing, stroke severity, and stroke subtype was performed. Strokes were adjudicated by neurologists blinded to treatment assignment. Stroke within 30 days, the primary safety outcome, was increased [33 (0.7%) vs. 16 (0.3%), hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.13-3.75]. The difference in stroke was apparent within 48 h [15 (0.3%) vs. 5 (0.1%), HR 3.00; 95% CI 1.09-8.25]. There was an increase in strokes within 180 days with minor or no disability (Rankin 0-2) [18 (0.4%) vs. 13 (0.3%) HR 1.38; 95% CI 0.68-2.82] and in strokes with major disability or fatal (Rankin 3-6) [35 (0.7%) vs. 13 (0.3%), HR 2.69; 95% CI 1.42-5.08]. Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [37 (0.7%) vs. 21 (0.4%), HR 1.71; 95% CI 1.03-3.00], but there was also an increase in haemorrhagic strokes [10 (0.2%) vs. 2 (0.04%), HR 4.98; 95% CI 1.09-22.7]. Patients that had a stroke had a mortality of 30.8% within 180 days vs. 3.4% without a stroke (P < 0.001). A meta-analysis of randomized trials (N = 21 173) showed an increase in risk of stroke (odds ratio 1.59; 95% CI 1.11-2.27) but a trend towards reduction in mortality odds ratio (odds ratio 0.87; 95% CI 0.76-1.00). CONCLUSION: Thrombectomy was associated with a significant increase in stroke. Based on these findings, future trials must carefully collect stroke to determine safety in addition to efficacy. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: TOTAL (N = 10 732), a randomized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction, showed no difference in the primary efficacy outcome but a significant increase in stroke. We sought to understand these findings. METHODS AND RESULTS: A detailed analysis of stroke timing, stroke severity, and stroke subtype was performed. Strokes were adjudicated by neurologists blinded to treatment assignment. Stroke within 30 days, the primary safety outcome, was increased [33 (0.7%) vs. 16 (0.3%), hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.13-3.75]. The difference in stroke was apparent within 48 h [15 (0.3%) vs. 5 (0.1%), HR 3.00; 95% CI 1.09-8.25]. There was an increase in strokes within 180 days with minor or no disability (Rankin 0-2) [18 (0.4%) vs. 13 (0.3%) HR 1.38; 95% CI 0.68-2.82] and in strokes with major disability or fatal (Rankin 3-6) [35 (0.7%) vs. 13 (0.3%), HR 2.69; 95% CI 1.42-5.08]. Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [37 (0.7%) vs. 21 (0.4%), HR 1.71; 95% CI 1.03-3.00], but there was also an increase in haemorrhagic strokes [10 (0.2%) vs. 2 (0.04%), HR 4.98; 95% CI 1.09-22.7]. Patients that had a stroke had a mortality of 30.8% within 180 days vs. 3.4% without a stroke (P < 0.001). A meta-analysis of randomized trials (N = 21 173) showed an increase in risk of stroke (odds ratio 1.59; 95% CI 1.11-2.27) but a trend towards reduction in mortality odds ratio (odds ratio 0.87; 95% CI 0.76-1.00). CONCLUSION: Thrombectomy was associated with a significant increase in stroke. Based on these findings, future trials must carefully collect stroke to determine safety in addition to efficacy. Published on behalf of the European Society of Cardiology. All rights reserved.
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