DETermination of the role of OXygen in suspected Acute Myocardial - PowerPoint PPT Presentation

DETermination of the role of OXygen in suspected Acute Myocardial Infarction Robin Hofmann, MD Karolinska Institutet Department of Clinical Science and Education Division of Cardiology, Södersjukhuset Stockholm, Sweden

Declaration of interest Unrestricted grants to fund the DETO2X-trial from • The Swedish Heart-Lung Foundation • The Swedish Research Council • The Swedish Foundation for Strategic Research No funding from the industry or for-profit organizations

Background (1) • Oxygen therapy has been used for more than a century and is widely recommended by guidelines despite limited evidence* *Roffi M, et al. Eur Heart J 2016; 37: 267-315. Steg PG, James SK, et al. Eur Heart J 2012; 33: 2569-619. • Rationale: Increased oxygen delivery to the ischemic myocardium reduces infarct size and subsequent complications

Background (2)

Background (3) • No high quality data from large RCTs available • The clinical effect of routine oxygen therapy in normoxemic patients 2016;12:CD007160 . with suspected AMI remains uncertain

Study Design DETO2X-AMI - A Registry-based Randomized Clinical Trial • National comprehensive quality registry of coronary care • All 69 Swedish hospitals with CCU participate • Coverage: >90% of all AMIs in Sweden Academic Research Organization Trial sponsor

Inclusion Criteria • Classical AMI symptoms < 6hours • Age ≥30 years • Oxygen saturation of ≥90 % • Significant ECG changes indicating ischemia or elevated troponin

Exclusion Criteria • Continuous ongoing oxygen therapy at home • Cardiac arrest prior to enrollment

Study Enrollment Patient contact with EMS, ED, CCU or cath lab Eligible patient Initial oral informed consent (written confirmation within 24h) Unrestricted online randomization using SWEDEHEART Oxygen Ambient Air Delivered by open face mask at 6L/min for 6-12 hours Data analysis through the Swedish Population Registry and SWEDEHEART

Primary Endpoint Death from any cause within 365 days after randomization in the intention-to-treat population

Sample Size and Analysis • Two-tailed superiority design • Clinically relevant effect defined as 20% risk reduction • 1-year all-cause mortality in AMI was estimated at 14% based on *Thang et al Int J Cardiol 2013;166:141-6 published* and historical** data **SWEDEHEART data 2005-2010 • Significance level of 0.05, 90% power = 2865 patients/group

Results 6629 Patients in DETO2X-AMI underwent randomization No patients were lost to follow-up for the primary endpoint 3311 Were assigned to the oxygen group and 3318 Were assigned to the ambient-air group included in the primary ITT analysis and included in the primary ITT analysis 62 Developed hypoxemia 254 Developed hypoxemia 106 Did not complete participation 297 Did not complete participation 3014 Were included in the secondary per- 3212 Were included in the secondary per- protocol analysis protocol analysis

DETO2X­AMI compared to other studies 0 1000 2000 3000 4000 5000 6000 7000 Hofmann, DETO2X-AMI (2017) COCHRANE Meta-analysis (2016) Stub, AVOID (2015) Ranchord (2012) Ukholkina (2005) Rawles (1976) Number of randomized patients with suspected AMI

Baseline Characteristics and Clinical Presentation Oxygen Ambient air (N=3311) (N=3318) Demographics – no. (%) Age – years, median (IQR) 68 (59-76) 68 (59-76) Male sex 2264 (68.4) 2342 (70.6) ­­­­­Risk factors – no. (%) Current smoking 704 (21.3%) 721 (21.7) Hypertension 1575 (47.6) 1559 (47.0) Diabetes mellitus 589 (17.8) 644 (19.4) Previous cardiovascular disease – no. (%) Myocardial infarction 682 (20.6) 667 (20.1) Percutaneous coronary intervention 525 (15.9) 549 (16.5) Presentation Ambulance transportation – no. (%) 2215 (66.9) 2218 (66.8) Oxygen saturation – %, median (IQR) 97 (95-98) 97 (95-98)

In-hospital procedures and complications Oxygen Ambient air (N=3311) (N=3318) Trial procedural data Duration of oxygen therapy – hours, median (IQR) 11.6 (6.0-12.0) x Oxygen saturation at end of treatment period† – %, 99 (97-100) 97 (95-98) median (IQR) Procedures – no. (%) Percutaneous coronary intervention 2183 (65.9) 2246 (67.7) Acute heart failure – no. (%) Use of iv diuretics 309 (9.3) 322 (9.7) Use of iv inotropes† 46 (1.4) 70 (2.1) Use of iv nitroglycerin 252 (7.6) 221 (6.7) Cardiogenic shock 32 (1.0) 37 (1.1) Complications – no. (%) Reinfarction 17 (0.5) 15 (0.5) Cardiac arrest 79 (2.4) 63 (1.9) Death 53 (1.6) 44 (1.3)

Discharge Diagnoses Final diagnosis – no. (%) Oxygen Ambient air (N=3311) (N=3318) Myocardial infarction 2485 (75.1) 2525 (76.1) Angina pectoris 189 (5.7) 185 (5.6) Other cardiac diagnosis 254 (7.7) 257 (7.7) Unspecified chest pain 258 (7.8) 234 (7.1) Other non-cardiovascular diagnosis 125 (3.8) 1117 (3.6)

Primary Endpoint up to 365 days Oxygen treatment Ambient air 5.1 % Ambient air Oxygen treatment 5.0 % HR 0.97 95% CI, 0.79 – 1.21 P=0.8

Primary Endpoint at 365 days in prespecified subgroups

Myocardial injury by Troponin T hs­cardiac Troponin T Oxygen Ambient air P (N=1998) (N=1978) Value ng/L* ­ median** 946.5 983.0 0.97 (IQR) (243-2884) (225-2931) * Confirmed AMI **Highest measured value during hospitalization Cumulative distribution of hs­Cardiac Troponin T according to treatment group

Conclusions • In this pragmatic, registry-based randomized clinical trial evaluating supplemental oxygen versus ambient air in patients presenting with suspected myocardial infarction who did not have hypoxemia, we did not find a beneficial effect of oxygen treatment with respect to all-cause mortality at 1 year. • The absence of an effect of supplemental oxygen on mortality was consistent in all prespecified subgroups, regardless of baseline characteristics or final diagnosis.

Acknowledgements Steering committee Robin Hofmann, Stefan James, Bertil Lindahl, Tomas Jernberg, David Erlinge, Nils Witt, Johan Herlitz, Leif Svensson (chair) Uppsala Clinical Research Centre (UCR) Ollie Östlund (statistics), Eva Jacobsson (project manager) We want to thank all DETO2X­SWEDEHEART investigators: Lena Forsman, Martin Risenfors, Oskar Angerås, Elmir Omerovic, Annica-Ravn Fisher, Björn Hornestam, Robert Kastberg, Espen Haugen, Markus Lingman, Anna Millbourn, Mats Frick, Thomas Kellerth, David Sparv, Ulf Ekelund, Rickard Linder, Urban Haaga, Ollie Östlund, Anders Engström, Jörg Carlsson, John Pernow, Linda Mellbin, Mattias Ekström, Fredrik Kjellberg, Raluca Jumatate, Lennart Malmqvist, Gull-Britt Eriksson, Joakim Alfredsson, Lennart Nilsson, Eva Swahn, Carina Nilsson, Krister Lindmark, Tommy Pettersson, Melvin Pourbazargan, Martin Serrander, Ivan Rosenqvist, Jörg Lauermann, Jan-Erik Karlsson, Magnus Peterson, Ylwa Wallström, Marianne Erlandsson, Ellinor Berglund, Troels Yndigegn, Bo Lagerqvist, Gabriel Arefalk, Christofer Digerfeldt, Olle Bergström, Björn Byström. and staffs of participating hospitals and EMS units for their commitment to this trial, and most of all, the patients willing to participate!