Does Oxygen Therapy Reduce Mortality in Myocardial Infarction?

Kenneth L. Smith, Mercer College of Pharmacy

Myocardial Infarction (MI), commonly known as a heart attack, is caused by a lack of oxygen to the myocardium, which leads to ischemia followed by cell death.[1] For more than a century, supplemental oxygen has been considered an integral part of treatment for suspected MI and is currently recommended in clinical guidelines.[2,3] The role of supplemental oxygen is to increase oxygen delivery to the myocardium tissue and prevent cell death. Above normal levels of oxygen can cause complications such as coronary vasoconstriction[4] and formation of reactive oxygen species[5]. Efficacy of routine oxygen therapy in patients with MI is considered uncertain.[6] In this randomized clinical trial, one year all-cause mortality benefits of routine oxygen therapy in patients with MI was explored.

Oxygen Therapy in Suspected Acute Myocardial Infarction [6]
Design Randomized controlled trial; N= 6,629
Objective To determine if supplemental oxygen in patients with suspected myocardial infarction, without hypoxemia, causes a reduction in all cause mortality within one year compared to ambient air
Study Groups Oxygen group (n= 3,311); ambient air (n= 3,318)
Methods Patients were required to be 30 years of age or older and to have symptoms suggestive of myocardial infarction for less than 6 hours with an oxygen saturation of 90% or higher. Participants also had to have either electrocardiographic changes indicating ischemia or elevated cardiac troponin T or I levels on admission. Follow-up was done through the Swedish National Population Registry. Volunteers were evaluated from various areas including ambulance services, emergency departments, coronary care units, or catheterization laboratories of participating hospitals.
Duration One year
Primary Outcome Measure Death from any cause within 1 year
Baseline Characteristics
Characteristics Oxygen Group

(n = 3311)

Ambient-Air Group

(n= 3318)

Value among patients with data available No. (%) of patients with missing data Value among patients with data available No. (%) of patients with missing data
Median age (IQR) — yr 68.0 (59.0–76.0) 0 68.0 (59.0–76.0) 0
Male sex — no. (%) 2264 (68.4) 0 2342 (70.6) 0
Body-mass index 27.1±4.4 92 (2.8) 27.2±4.4 105 (3.2)
Current smoker — no. (%) 704 (21.3) 129 (3.9) 721 (21.7) 127 (3.8)
Hypertension — no. (%) 1575 (47.6) 42 (1.3) 1559 (47.0) 39 (1.2)
Diabetes mellitus — no. (%) 589 (17.8) 24 (0.7) 644 (19.4) 31 (0.9)
Previous cardiovascular disease — no. (%)
Myocardial infarction 682 (20.6) 29 (0.9) 667 (20.1) 33 (1.0)
PCI 525 (15.9) 36 (1.1) 549 (16.5) 37 (1.1)
CABG 208 (6.3) 32 (1.0) 206 (6.2) 36 (1.1)
Cause of admission — no. (%) 28 (0.8) 30 (0.9)
Chest pain 3123 (94.3) 3120 (94.0)
Dyspnea 63 (1.9) 77 (2.3)
Cardiac arrest 1 (<0.1) 1 (<0.1)
Medication at admission — no. (%)
Aspirin (27.3) 44 904 (1.3) 961 (29.0) 49 (1.5)
P2Y12 receptor inhibitor 177 (5.3) 43 (1.3) 173 (5.2) 51 (1.5)
Beta-blocker 1030 (31.1) 54 (1.6) 1052 (31.7) 58 (1.7)
Statin 884 (26.7) 48 (1.4) 895 (27.0) 47 (1.4)
ACE inhibitor or angiotensin II blocker 1186 (35.8) 55 (1.7) 1237 (37.3) 62 (1.9)
Calcium 617 (18.6) 53 (1.6) blocker 615 (18.5) 59 (1.8)
Diuretic 543 (16.4) 55 (1.7) 525 (15.8) 54 (1.6)
Median time from symptom onset to randomization

(IQR) — min

245.0 (135.0–450.0) 481 (14.5) 250 (134.0–458.0) 463 (14.0)
Ambulance transportation — no. (%) 2215 (66.9) 47 (1.40 2218 (66.8) 39 (1.2)
Vital signs at presentation
Systolic blood pressure — mm Hg 150.3±27.8 28 (0.8) 148.7±28.0 28 (0.8)
Heart rate — beats/min 78.6±19.3 27 (0.8) 78.1±19.5 27 (0.8)
Median oxygen saturation (IQR) — % 97 (95–98) 0 97 (95–98) 0
Final diagnosis — no. (%) 0 0
Myocardial infarction 2485 (75.1) 2525 (76.1)
STEMI 1431 (43.2) 1521 (45.8)
Angina pectoris 189 (5.7) 185 (5.6)
Other cardiac diagnosis 254 (7.7) 257 (7.7)
Atria fibrillation 52 (1.6) 44 (1.3)
Heart failure 43 (1.3) 40 (1.2)
Cardiomyopathy 48 (1.4) 46 (1.4)
Perimyocarditis 32 (1.0) 43 (1.3)
Pulmonary embolism 7 (0.2) 9 (0.3)
Pulmonary disease 17 (0.5) 15 (0.5)

 

Pneumonia 8 (0.2) 7 (0.2)

 

COPD or asthma 2 (0.1) 2 (0.1)

 

Unspecified chest pain 258 (7.8) 234 (7.1)

 

Other, noncardiovascular diagnosis 108 (3.3) 102 (3.1)

 

Musculoskeletal pain 7 (0.2) 14 (0.4)

 

Results
Table 1. Mortality during hospitalization
Event Oxygen group

(n = 3311)

Ambient-air group

(n = 3318)

p value
Value among patients with data available No. (%) of patients with missing data Value among patients with data available No. (%) of patients with missing data  
Death 53 (1.6) 28 (0.8) 44 (1.3) 26 (0.8) 0.35

 

 

Table 2. Endpoints during and after hospitalization
Timing and endpoint Oxygen group

(n = 3311)

Ambient air group

(n  = 3318)

Hazard ratio

(95% CI)

p  value
365 days after randomization
Death from any cause — no. (%) 166 (5.0) 168 (5.1) 0.97 (0.79–1.21) 0.80

 

Composite of death from any cause or rehospitalization

with myocardial infarction — no. (%)

 

275 (8.3) 264 (8.0) 1.03 (0.87–1.22) 0.70

 

30 Days after randomization
Death from any cause — no. (%) 73 (2.2) 67 (2.0) 1.07 (0.77–1.50) 0.67

 

Composite of death from any cause or rehospitalization

with myocardial infarction — no. %)

 

114 (3.4) 95 (2.9) 1.19 (0.91–1.56) 0.21

 

During hospital stay
Adverse Events Common adverse events: N/A
Serious adverse events: N/A
Percentage that discontinued due to adverse events: N/A
Study Author Conclusions There was no beneficial effect found with the use of oxygen treatment with respect to all-cause mortality at one year.

This study concluded that one year all-cause mortality was not reduced in patients with MI in the absence of hypoxemia. A reported limitation in this study was the lack of pressurized air in Swedish ambulances and the inability to use a Hudson mask due to a risk of carbon dioxide retention. Since certain patients couldn’t use pressurized air or mask, blinding was limited in the study. The study was designed not to include those with hypoxemia even though these patients contribute considerably to the total mortality of a substantial number of MI patients that were excluded.  It is unclear if this exclusion would alter the  mortality result had they been included in the study.

References:

[1] Cairns JA. Myocardial infarction size: measurement and modification. Can Med Assoc J. 1977;117(3):255-62.

[2] Steg PG, James SK, Atar D, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33: 2569-619.

[3] Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37: 267-315.

[4] Moradkhan R, Sinoway LI. Revisiting the role of oxygen therapy in cardiac patients. J Am Coll Cardiol 2010; 56: 1013-6.

[5] Zweier JL, Talukder MAH. The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 2006; 70: 181-90.

[6] Hofmann R, James SK, Jernberg T, et al. Oxygen therapy in suspected acute myocardial infarction. N Engl J Med. DOI: 10.1056/NEJMoa1706222.

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