Inexpensive Drug Costing Less $3 May Minimize Damage from Heart Attack

October 2, 2013 — Early treatment of heart attack patients with an inexpensive beta-blocker drug called metoprolol, while in transit to the hospital, can significantly reduce damage to the heart during a myocardial infarction, according to clinical trial/study results published Oct. 1 in the journal Circulation. The study was a collaboration between Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Icahn School of Medicine at Mount Sinai.

The study, involving emergency ambulances and seven hospitals across Spain, shows the simple, low-cost intervention strategy with metoprolol could be easily extended throughout the world to provide significant clinical benefit and could change current treatment practice for heart attack patients. Currently, patients receive no medication before undergoing routine angioplasty.

Borja Ibáñez, M.D., Ph.D., head of the Experimental Cardiology Group at CNIC and clinical cardiologist at the Hospital Clínico San Carlos in Spain, is the joint lead investigator of this novel study with Valentín Fuster, M.D., Ph.D., general director of CNIC, who also serves as director of Mount Sinai Heart and physician-in-chief at The Mount Sinai Medical Center.

Metoprolol, a drug of the beta-blocker family, has been available for more than 30 years to treat arterial hypertension and other cardiovascular conditions. In this new study, the team of researchers was able to examine the potential usefulness of metoprolol after a heart attack. The clinical trial named METOCARD-CNIC is the first to test metoprolol therapy, at a cost less than $3 (less than 2 euros), in heart attack patients undergoing standard angioplasty treatment procedures.

According to researchers, the potential savings from this medical therapy intervention may go far beyond the low cost of metoprolol itself, since patients experiencing less-extensively damaged heart muscle are less likely to need more costly treatments such as an implantable defibrillator or require costly hospitalization for treatment of heart failure.

“The savings in healthcare costs will run into millions; a per-patient outlay of less than two euros will over the years save thousands,” explained Ibáñez. Currently, researchers are carrying out a cost-effectiveness analysis to provide a firm estimate of the expected savings.

According to researchers, the best strategy for limiting the size of an infarct is to carry out the angioplasty procedure as soon as possible. A delay in reopening the coronary artery could mean a larger region of damaged or necrotic tissue. When necrosis is extensive, the heart loses a large part of its pumping strength, which does not recover.

In addition to the high risk of death during the infarction, survivors are likely to suffer from heart failure and severe arrhythmias, and often die in the months or years following the attack.

“The larger the infarct (death of cardiac muscle), the greater the probability that survivors will suffer these complications in the future,” said Fuster.

Therefore, Fuster stressed reducing the amount of tissue that is damaged or dies during an infarction is of the utmost importance. Over the last several decades, investigators have searched unsuccessfully for a complementary therapy that would further reduce the extent of heart damage.

A total of 270 patients with infarction were recruited since 2010 in four of Spain’s regions. In the randomized study, patients were assigned to receive either intravenous metoprolol or a placebo treatment at the moment of diagnosis of a myocardial infarction during ambulance transit to the catheterization laboratory.

The efficacy of the medical intervention was evaluated by magnetic resonance imaging (MRI) a week after the infarction. MRI measured the mass of damaged heart tissue in all patients. The results showed patients who received metoprolol had much smaller infarcts than those who received the control treatment, and that this smaller infarct size was linked to greater heart contractility.

The MRI scans were analyzed at the central CNIC laboratory by cardiologists blinded to the treatment.

Preclinical research findings on metoprolol in animal models, analyzed using MRI and published in the journal Circulation in 2007, showed early administration of metoprolol during heart attack increased myocardial salvage and led to the translational medicine potential for human clinical trial.

The research team is currently investigating the molecular mechanism underlying the therapeutic action of metoprolol.

“This project analyzes the effect of metoprolol on the interaction of blood platelets with inflammatory cells, which might explain the benefit of early treatment with this drug as soon as possible after diagnosis of a heart attack,” explained Antonio Fernández-Ortiz, M.D., Ph.D., co-investigator, METOCARD-CNIC study and leader of this sub-study

Researchers are planning to extend the clinical trial to a larger number of patients in a multinational study to demonstrate not only a reduced infarct size but also a reduced mortality in patients who receive metoprolol during transit to hospital. The CNIC research team, colleagues in the emergency services and hospitals are already working on the logistics of a new international clinical trial.

In an editorial accompanying the published article in Gjin Ndrepepa and Adnan Kastrati, experts from the Technische Universität and the Munich Heart Alliance, affirmed that, if confirmed by a subsequent analysis of large numbers of patients, the results of METOCARD-CNIC trial are likely to lead to a change in clinical practice.

For more information: www.mountsinai.org