Heart attack treatment - ERIC-PPCI

The clinical question

Currently, the best way to reduce damage after a heart attack and improve chances of survival is to restore blood flow to heart muscle as quickly as possible, using a treatment called primary percutaneous coronary intervention (PPCI). But PPCI is not without risk. Rapidly restoring blood flow to the heart can unexpectedly damage heart muscle. This process is called ‘ischaemia-reperfusion injury’, and can contribute to heart failure developing.

There is some evidence that the heart and other organs can be protected against ischaemia-reperfusion injury by ‘remote ischaemic conditioning’. Here, blood flow to the arm or leg is repeatedly restricted and restored using a blood pressure cuff. In some small studies, researchers found that this simple treatment could reduce the amount of damaged heart muscle in people who have had a heart attack and are receiving PPCI. But a larger study was needed to find out whether remote ischaemic conditioning could improve clinical outcomes for people receiving PPCI in the longer term.

The BHF funded the trial ‘Effect of Remote Ischaemic Conditioning on clinical outcomes in ST-segment elevation myocardial infarction patients undergoing Primary Percutaneous Coronary Intervention’ (ERIC-PPCI) led by Professor Derek Hausenloy and Professor Derek Yellon at University College London, Professor Rajesh Kharbanda at the John Radcliffe Hospital and Professor Tim Clayton at London School of Hygiene and Tropical Medicine. The results of this trial, which involved 26 UK hospitals, were combined with another trial (CONDI-2) taking place across Denmark, Spain and Serbia. CONDI-2 was led by Professor Hans Erik Bøtker at Aarhus University, Denmark. This maximised the number of people taking part, with the aim of getting a definitive answer to this question.

What did the study involve?

Between 2013 and 2018, CONDI-2/ERIC-PPCI randomly assigned 5401 people undergoing PPCI to receive either:

• Remote ischaemic conditioning, given before undergoing PPCI, either in the ambulance or on arrival at the hospital. This consisted of four 5-minute inflations and deflations of an automated blood-pressure cuff on their upper arm.

• Sham conditioning followed by standard medical treatment. Sham conditioning consisted of using an identical looking device which did not actually inflate. Participants in non-UK sites did not receive sham conditioning but were given standard medical treatment.

Participants were followed up for 1 year following the procedure. The team recorded:

• If the participants died due to a heart-related cause.

• If they were hospitalised for heart failure.

• A subset of participants also had blood samples taken following PPCI to measure levels of a molecule called troponin in their blood. Troponin is released from heart muscle when it is damaged.

What did the study show?

• The study did not show any evidence of protection after remote ischaemic conditioning.
• The number of people who died or were hospitalised for heart failure was similar between the two groups.
• The study also did not show any difference in levels of troponin between the treatment and control groups, suggesting that remote ischaemic conditioning did not reduce heart muscle damage.

Why is the study important?

The CONDI-2/ERIC-PPCI trial was the first large randomised clinical trial to test whether remote ischaemic conditioning affected long term clinical outcomes in PPCI patients. It was important to perform this trial given previous promising results from studies in animals and smaller clinical trials. The trial is also a good example of international collaboration in research – the collective efforts of the ERIC-PPCI team in the UK and CONDI-2 teams across Europe ensured that the trial recruited quickly and successfully, yielding a definitive answer to this important clinical question.  

The results were presented at the 2019 European Society of Cardiology conference by the lead investigator of the CONDI-2 arm, Professor Hans Erik Bøtker. Professors Bøtker and Hausenloy agreed that: 

Disappointing but definitive, the results of this trial spell the end for RIC in preventing damage to the heart in lower risk heart attack patients who receive timely and optimal PPCI treatment. However, RIC may still be beneficial in higher risk patients such as those heart attack patients presenting with heart failure, or in countries where PPCI treatment is either delayed or not available. Therefore, the search for effective ways to protect the heart will continue, and this result will help to shift the focus of this research into new areas. 

Study details

“Effect of Remote Ischaemic Conditioning on clinical outcomes in ST-segment elevation myocardial infarction patients undergoing Primary Percutaneous Coronary Intervention (ERIC-PPCI): A multi-centre randomised controlled clinical study.”
Award reference:  CS/14/3/31002
Principal Investigator: Professor Derek Hausenloy, University College London
Trial registration number: NCT02342522

Publication details

Hausenloy DJ, Kharbanda RK, Møller UK, et al. Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet. 2019;394(10207):1415-1424.