NIHR Signal No benefit from therapeutic cooling after a major heart attack

Published on 26 April 2016

There is no evidence at present that therapeutic cooling after a major heart attack could prevent death or future heart attacks. Therapeutic cooling, also called therapeutic hypothermia, or targeted temperature management, involves artificially reducing the body temperature by a few degrees, here to under 35˚C. This approach is recommended in NICE guidance to help protect brain function after cardiac arrest, but not for heart attack.

Recent treatments involving stents or clot busting drugs have helped greatly improve survival rates after heart attack, and cooling was tested as a possibility for further protecting heart function in people who had suffered a full thickness heart attack. The findings show that therapeutic cooling does not reduce mortality nor major adverse cardiac events overall. It might reduce the amount of the heart damaged but this was only found in the group of people with heart damage on the front of the heart, and could be a chance finding.

Further research may help understand whether cooling may help and if there are particular patient groups who might benefit, though any benefits or harms are likely to be small.

No benefit from therapeutic cooling after a major heart attack

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Why was this study needed?

Heart attacks are a major cause of death and ill health. In 2013, NICE estimated that there were 500 hospital admissions per million people for the type of heart attack studied in this review – STEMI (see Definitions) – which is common.

In recent decades, new and faster treatments have helped reduce the death rate by three quarters. These treatments include clot busting drugs (fibrinolysis) and balloon catheters with stents (a percutaneous intervention), and they work by unblocking the arteries supplying heart muscle. The researchers were interested in testing whether this treatment might lead to improved outcomes.

Previous trials and systematic reviews had found that therapeutic cooling of the body (for example, using cooling pads or ice packs to reduce the body temperature to 32-34˚C) protects brain function in the aftermath of a cardiac arrest.

However, there is limited evidence from small trials about whether therapeutic cooling could protect the heart muscle itself. A review and meta-analysis was needed to determine whether pooled trial results would show a beneficial effect.

What did this study do?

This systematic review focussed on trials of therapeutic cooling for adults who had experienced one of the most serious types of heart attack – STEMI.

In the six included trials, the researchers looked for reporting of major adverse cardiac events. This term generally covers situations such as death or recurrence of heart attack, but the definition varied between the trials included in this review. Neither did the included trials have a standard approach to cooling. Most of the studies used cooling catheters to reduce temperature, but the target temperature, and the extent and duration of cooling varied between studies, with some not achieving 35˚C. These differences in cooling, and the relatively small number of the deaths and cardiac events may mean that there could be benefits or harms from thorough cooling but those are likely to be quite small.

The researchers looked for bias in the trials and report that this was not an issue. If anything bias would tend to increase any effect so is unlikely to explain the finding of little or no benefit here.

What did it find?

The pooled trial results included 819 participants.

  • There was no significant difference in the occurrence of major adverse cardiac events up to 30 days between participants who received therapeutic cooling (31 events in 410 people) and those who did not receive therapeutic cooling (27 events in 409 people). Odds ratio 1.04 (95% confidence interval (CI) 0.37 to 2.89).
  • Death rates were also not significantly affected by cooling (16/410 with cooling v 11/409 without cooling).
  • An analysis of subgroups within the studies suggested that anterior wall infarcts, at the front of the heart were, on average, smaller following cooling. Standardised difference was - 0.23 (95% CI -0.02 to -0.45). This finding was not seen in all infarcts and was one of many analyses undertaken so may have been a chance finding.

What does current guidance say on this issue?

No guidance was found on therapeutic cooling for the purpose of protecting heart muscle.

There has been evidence that therapeutic cooling can protect brain function rather than heart muscle after cardiac arrest and this is included within NICE interventional guidance from 2011 on the management of cardiac arrest as well as American Heart Association guidance from 2010.

NICE clinical guidance on heart attack published in 2013 does not mention therapeutic cooling.

What are the implications?

Given the lack of evidence that therapeutic cooling saves lives or protects heart function, there is no reason at present to use the procedure after heart attack, unless this has led to cardiac arrest.

Even though there were over 800 people included in these trials, the outcome events were quite uncommon and confidence intervals were very wide, so benefits or harms could have been missed in this study. However, even if these exist they are likely to be small. The review authors identified priorities for possible future research in different situations, such as in more selected people and using greater cooling, but this study offers little indication that cooling could be helpful enough to justify a large future trial.

Citation and Funding

Villablanca PA, Rao G, Briceno DF, et al. Therapeutic hypothermia in ST elevation myocardial infarction: a systematic review and meta-analysis of randomised control trials. Heart. 2016;102(9):712-9.

No funding information was provided for this study.

Bibliography

NHS Choices. Heart attack. Leeds: NHS Choices; 2014.

NICE. Myocardial infarction with ST-segment elevation: acute management. CG167. London: National Institute for Health and Care Excellence; 2013.

NICE. Therapeutic hypothermia following cardiac arrest. IPG386. London: National Institute for Health and Care Excellence; 2011.

Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 Suppl 3):S768–86. 

Why was this study needed?

Heart attacks are a major cause of death and ill health. In 2013, NICE estimated that there were 500 hospital admissions per million people for the type of heart attack studied in this review – STEMI (see Definitions) – which is common.

In recent decades, new and faster treatments have helped reduce the death rate by three quarters. These treatments include clot busting drugs (fibrinolysis) and balloon catheters with stents (a percutaneous intervention), and they work by unblocking the arteries supplying heart muscle. The researchers were interested in testing whether this treatment might lead to improved outcomes.

Previous trials and systematic reviews had found that therapeutic cooling of the body (for example, using cooling pads or ice packs to reduce the body temperature to 32-34˚C) protects brain function in the aftermath of a cardiac arrest.

However, there is limited evidence from small trials about whether therapeutic cooling could protect the heart muscle itself. A review and meta-analysis was needed to determine whether pooled trial results would show a beneficial effect.

What did this study do?

This systematic review focussed on trials of therapeutic cooling for adults who had experienced one of the most serious types of heart attack – STEMI.

In the six included trials, the researchers looked for reporting of major adverse cardiac events. This term generally covers situations such as death or recurrence of heart attack, but the definition varied between the trials included in this review. Neither did the included trials have a standard approach to cooling. Most of the studies used cooling catheters to reduce temperature, but the target temperature, and the extent and duration of cooling varied between studies, with some not achieving 35˚C. These differences in cooling, and the relatively small number of the deaths and cardiac events may mean that there could be benefits or harms from thorough cooling but those are likely to be quite small.

The researchers looked for bias in the trials and report that this was not an issue. If anything bias would tend to increase any effect so is unlikely to explain the finding of little or no benefit here.

What did it find?

The pooled trial results included 819 participants.

  • There was no significant difference in the occurrence of major adverse cardiac events up to 30 days between participants who received therapeutic cooling (31 events in 410 people) and those who did not receive therapeutic cooling (27 events in 409 people). Odds ratio 1.04 (95% confidence interval (CI) 0.37 to 2.89).
  • Death rates were also not significantly affected by cooling (16/410 with cooling v 11/409 without cooling).
  • An analysis of subgroups within the studies suggested that anterior wall infarcts, at the front of the heart were, on average, smaller following cooling. Standardised difference was - 0.23 (95% CI -0.02 to -0.45). This finding was not seen in all infarcts and was one of many analyses undertaken so may have been a chance finding.

What does current guidance say on this issue?

No guidance was found on therapeutic cooling for the purpose of protecting heart muscle.

There has been evidence that therapeutic cooling can protect brain function rather than heart muscle after cardiac arrest and this is included within NICE interventional guidance from 2011 on the management of cardiac arrest as well as American Heart Association guidance from 2010.

NICE clinical guidance on heart attack published in 2013 does not mention therapeutic cooling.

What are the implications?

Given the lack of evidence that therapeutic cooling saves lives or protects heart function, there is no reason at present to use the procedure after heart attack, unless this has led to cardiac arrest.

Even though there were over 800 people included in these trials, the outcome events were quite uncommon and confidence intervals were very wide, so benefits or harms could have been missed in this study. However, even if these exist they are likely to be small. The review authors identified priorities for possible future research in different situations, such as in more selected people and using greater cooling, but this study offers little indication that cooling could be helpful enough to justify a large future trial.

Citation and Funding

Villablanca PA, Rao G, Briceno DF, et al. Therapeutic hypothermia in ST elevation myocardial infarction: a systematic review and meta-analysis of randomised control trials. Heart. 2016;102(9):712-9.

No funding information was provided for this study.

Bibliography

NHS Choices. Heart attack. Leeds: NHS Choices; 2014.

NICE. Myocardial infarction with ST-segment elevation: acute management. CG167. London: National Institute for Health and Care Excellence; 2013.

NICE. Therapeutic hypothermia following cardiac arrest. IPG386. London: National Institute for Health and Care Excellence; 2011.

Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 Suppl 3):S768–86. 

Therapeutic hypothermia in ST elevation myocardial infarction: a systematic review and meta-analysis of randomised control trials

Published on 13 February 2016

Villablanca, P. A.,Rao, G.,Briceno, D. F.,Lombardo, M.,Ramakrishna, H.,Bortnick, A.,Garcia, M.,Menegus, M.,Sims, D.,Makkiya, M.,Mookadam, F.

Heart , 2016

OBJECTIVE: Our objective is to gain a better understanding of the efficacy and safety of therapeutic hypothermia (TH) in patients with acute ST elevation myocardial infarction (STEMI) through an analysis of randomised controlled trials (RCTs). BACKGROUND: Several RCTs have suggested a positive outcome with the use of TH in the prevention of myocardial injury in the setting of an acute STEMI. However, there are currently no clinical trials that have conclusively shown any significant benefit. METHODS: Electronic databases were used to identify RCTs of TH in the patient population with STEMI. The primary efficacy end point was major adverse cardiovascular event (MACE). Secondary efficacy end points included all-cause mortality, infarct size, new myocardial infarction and heart failure/pulmonary oedema (HF/PO). All-bleeding, ventricular arrhythmias and bradycardias were recorded as the safety end points. RESULTS: Six RCTs were included in this meta-analysis, enrolling a total of 819 patients. There was no significant benefit from TH in preventing MACE (OR, 01.04; 95% CI 0.37 to 2.89), all-cause mortality (OR, 1.48; 95% CI 0.68 to 3.19), new myocardial infarction (OR, 0.99; 95% CI 0.20 to 4.94), HF/PO (OR, 0.52; 95% CI 0.15 to 1.77) or infarct size (standard difference of the mean (SDM), -0.1; 95% CI -0.23 to 0.04). However, a significant reduction of infarct size was observed with TH utilisation in anterior wall myocardial infarction (SDM, -0.23; 95% CI -0.45 to -0.02). There was no significant difference seen for the safety end points all-bleeding (OR 1.32; 95% CI 0.77 to 2.24), ventricular arrhythmias (OR, 0.85; 95% CI 0.54 to 1.36) or bradycardias (OR, 1.16; 95% CI 0.74 to 1.83). CONCLUSIONS: Although TH appears to be safe in patients with STEMI, meta-analysis of published RCTs indicates that benefit is limited to reduction of infarct size in patients with anterior wall involvement with no demonstrable effect on all-cause mortality, recurrent myocardial infarction or HF/PO.

A heart attack, or myocardial infarction, occurs when the blood supply to the heart muscle is suddenly blocked by a clot. The blockage starves the heart muscle of oxygen, and unless the supply can be restored quickly, for example using surgery or by clot-busting drugs, there is a high risk of permanent damage to the heart muscle.

One of the most serious types of heart attack is called STEMI (ST-segment elevation myocardial infarction), as defined by the trace it produces on an electrocardiogram. The elevation implies a heart attack that extends across the full thickness of heart muscle originating from complete blockage of an artery supplying this area.

Expert commentary

Does therapeutic hypothermia have anything to offer patients having an acute myocardial infarction? As ever, small studies suggest that there might be some benefit, but this meta-analysis of trials involving over 800 patients shows no evidence of benefit. The confidence intervals around the result are so wide that it is possible considerable harm might be being done by therapeutic hypothermia. A definitive trial is needed  and in the interim, therapeutic hypothermia should join the list of potential post myocardial infarction interventions that sound attractive, but turn out not to be - such as the routine use of anti-arrhythmic drugs and oxygen.

Professor Andrew L Clark, Chair of Clinical Cardiology and Honorary Consultant Cardiologist, Castle Hill Hospital, Cottingham

Categories

  •   Cardiovascular system disorders, Acute and general medicine