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*

• Rationale: Increased oxygen delivery to the ischemic

myocardium reduces infarct size and subsequent complications

*Roffi M, et al. Eur Heart J 2016; 37: 267-315. Steg PG, James SK, et al. Eur Heart J 2012; 33: 2569-619.

Background (2)

Background (3)

• No high quality data from large

RCTs available

• The clinical effect of routine oxygen

therapy in normoxemic patients with suspected AMI remains uncertain

2016;12:CD007160.

Study Design

• National comprehensive quality

registry of coronary care

• All 69 Swedish hospitals with CCU

participate

• Coverage: >90% of all AMIs in Sweden

Trial sponsor Academic Research Organization

DETO2X-AMI - A Registry-based Randomized Clinical Trial

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

Delivered by open face mask at 6L/min for 6-12 hours

Ambient Air

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

published* and historical** data

• Significance level of 0.05, 90% power = 2865 patients/group

*Thang et al Int J Cardiol 2013;166:141-6 **SWEDEHEART data 2005-2010

Results

6629 Patients in DETO2X-AMI underwent randomization 3311 Were assigned to the oxygen group and

included in the primary ITT analysis 62 Developed hypoxemia 297 Did not complete participation 3014 Were included in the secondary per- protocol analysis

3318 Were assigned to the ambient-air group

and included in the primary ITT analysis 254 Developed hypoxemia 106 Did not complete participation 3212 Were included in the secondary per- protocol analysis

No patients were lost to follow-up for the primary endpoint

DETO2X­AMI compared to other studies

7000 6000 5000 4000 3000 2000 1000

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 (N=3311) Ambient air (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 (N=3311) Ambient air (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† – %, median (IQR) 99 (97-100) 97 (95-98) 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 (N=3311) Ambient air (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

Ambient air Oxygen treatment

HR 0.97 95% CI, 0.79 – 1.21 P=0.8

Oxygen treatment 5.0 % Ambient air 5.1 %

Primary Endpoint at 365 days in prespecified subgroups

Myocardial injury by Troponin T

Cumulative distribution of hs­Cardiac Troponin T according to treatment group hs­cardiac Troponin T Oxygen (N=1998) Ambient air (N=1978) P Value ng/L* ­ median** (IQR) 946.5 (243-2884) 983.0 (225-2931) 0.97

* Confirmed AMI **Highest measured value during hospitalization

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!