REBOOT

In March 2019, CNIC (the Spanish National Centre for Cardiovascular Research) and the Spanish Society of Cardiology (SEC) presented a pioneering project in Spain. TREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT). In the words of its principal investigator, Dr. Borja Ibáñez, this project “...has the ambitious vocation to change clinical practice guidelines after acute myocardial infarction.” To do so, the effect of maintaining beta blocker treatment after hospital discharge for heart attack will be tested among 8,468 patients. To date, over 6,000 patients have been recruited.

Beta blockers are drugs that reduce heart rate, blood pressure and myocardial contractility (the heart’s strength) favouring diastole (refill) of the heart and, therefore, improved heart function and blood flow to the coronary arteries. Despite most evidence dating from a time when reperfusion therapy was not given to patients, for decades, beta blockers have been approved by all European and American clinical practice guidelines for treatment of patients after acute myocardial infarction.

Currently, clinical practice guidelines recommend beta blockers. However, this approval is based on trials carried out decades ago when the treatment for heart attack was less sophisticated, at a time before reperfusion therapy. At that time, coronary arteries were not unblocked and the prognosis for patients was a lot worse than nowadays.

Today, patients who survive acute myocardial infarction without deterioration of the heart’s ability to pump blood have a much better prognosis and, therefore, we need to take a fresh look at whether beta blockers continue to offer clinical benefits.

Specifically, for the first time in the era of reperfusion therapy, REBOOT aims to study whether administering beta blockers to this type of patient influences the incidence of death, reinfarction or hospital admission for heart failure.

For more than four decades, beta blocker drugs have almost universally been prescribed on discharge after acute myocardial infarction (AMI), despite the fact that there is no clear evidence of their benefit for all types of infarction.

Several thousand researchers and over 100 small, medium and large hospitals in Spain and Italy will participate in REBOOT, which aims to change the clinical practice guidelines related with myocardial infarction

Although the precise figures are difficult to calculate, in Spain each year there are approximately 100,000 heart attacks without left ventricular systolic dysfunction. Almost all of these patients are discharged with a prescription of two antiplatelet drugs (aspirin and a P2Y12 inhibitor), statins, ACE inhibitors, beta blockers and a gastric protector. In many cases other types of medication are associated. Except for the P2Y12 inhibitor and the gastric protector, the other medication is currently prescribed for life.

Beta blockers, despite being inexpensive (they are no longer under patent) and having a very high safety profile, may have potential adverse reactions that could limit a patient’s quality of life, which include physical weakness, loss of strength and, in some cases, impotence. We should consider that may patients who suffer a heart attack are middle-aged, have many years of life ahead of them, and their quality of life is an important factor to bear in mind. This is why knowing whether this type of drug is really necessary for these patients is of major importance. If it is shown that they are not effective in this type of post-infarction patient, they will not be prescribed, which could result in an increase of patient adherence to medication that has been shown to be effective, and also avoid possible adverse reactions that might limit patient quality of life.

The study will recruit a total 8,500 patients who have suffered a myocardial infarction with a left ventricular ejection fraction greater than 40%, who will be randomised to receive a placebo or beta blockers.

They will undergo a minimum two-year, maximum three-year follow-up. The incidence of clinical events and adherence to the randomised treatment will be recorded and documented at 3, 15 and 36 months. A sub-sample of 1,000 patients will be used to assess patient quality of life during follow-up.

Dr. Borja Ibáñez, principal investigator of the REBOOT study, comments that several thousand researchers and over 100 small, medium and large hospitals in Spain and Italy will participate in REBOOT, which aims to change the clinical practice guidelines related with myocardial infarction.

The study will be coordinated by CNIC’s Clinical Trials Coordination Unit, and will compile data on the incidence of death, reinfarction or hospitalization for heart failure among the patients during a three-year follow-up.

This is the first large-scale, independent clinical trial developed in and led by our country. To date, it has not been possible to undertake a study of this size without a connection to industry.

Beta blockers, despite being inexpensive and having a very high safety profile, may have potential adverse reactions that could limit a patient’s quality of life, which include physical weakness, loss of strength and, in some cases, impotence

“The study design is highly innovative, in that it is a pragmatic trial closely related to real life, which is to say, there are no great restrictions as far as inclusion criteria are concerned...” Dr. Ibáñez comments, “...although the most novel aspect of this trial is that it is the first large-scale study to be carried out in our country that has no connection with industry. This type of study is common in countries like Sweden or the United Kingdom, but so far not in Spain. Spain has a great deal of talent, but so far it has been difficult to get any project of this nature off the ground,” he adds.

The subject under study is of such clinical relevance that another three clinical trials similar to REBOOT are to start in Sweden, Norway and Denmark. In total there will be over 20,000 patients with similar characteristics, randomised to receive a placebo or beta blockers after a heart attack without ventricular dysfunction. “The fact that different studies are going ahead simultaneously will not only measure our capacity to be on a par with counties that have a tradition of carrying out large-scale clinical trials, but also allow us to perform meta-analysis by pooling all of the cohorts,” Dr. Ibáñez concludes.