By Nancy Lapid

Aug 30 (Reuters) - A decades-old pill remains helpful for heart attack patients even with modern treatments that can prevent lasting damage to heart muscle, two large trials have shown.

Still unclear is whether all patients, or only some, benefit from so-called beta-blocker drugs, which are typically prescribed to everyone after a heart attack.

Two sharply contradictory reports were presented on Saturday at a large cardiology meeting in Madrid and published in The New England Journal of Medicine.

“It is not unusual for trials to yield different results,” said Dr. Borja Ibanez of Centro Nacional de Investigaciones Cardiovasculares Carlos III in Madrid, who led one of the trials.

“Somewhat uncommon is to see two trials with apparently divergent findings presented on the same day.”

Most important, Ibanez said, is the finding both teams agree on, which is that beta-blockers reduce the combined risk of another heart attack, heart failure, or death in patients without heart failure but with mildly impaired heart function.

The question is whether the pills are beneficial or useless for those with normally functioning hearts, who account for about 80% of patients after a first heart attack.

Beta-blocker manufacturers include Mylan, Novartis NOVN.S, Pfizer PFE.N, Abbott, Teva Pharmaceutical Industries TEVA.TA, Amneal Pharmaceuticals AMRX.O, Sun Pharmaceutical Industries SUN.NS, Lupin, ANI Pharmaceuticals ANIP.O, and Eagle Pharmaceuticals EGRX.PK.

The drugs work by inhibiting the hormones epinephrine and norepinephrine, thereby lowering heart rate and blood pressure, decreasing the workload on the heart and reducing its oxygen demand.

Both new trials involved heart attack survivors whose hearts were still contracting normally, that is, the left ventricle was pumping out at least 40% of its blood with each beat. Both trials followed patients for roughly 3.5 years.

Among 5,574 volunteers in the BETAMI–DANBLOCK study from Norway and Denmark, the drugs showed a clear benefit. Patients randomly assigned to receive beta-blockers had a 15% lower risk of death or major adverse cardiovascular event, particularly a repeat heart attack, compared to patients not taking these pills, investigators found.

But among the 8,438 participants in the REBOOT trial conducted in Italy and Spain, beta-blockers had no effect on the incidence of death from any cause, a repeat heart attack, or hospitalization for heart failure, according to a separate report.

Some of the difference may be due to the fact that patients didn't all receive the same beta-blockers, and the Scandinavian patients might have been more prone to adverse events because they were slightly older than patients in Spain and Italy and more of them had mild heart dysfunction, said Dr. Dan Atar of the University of Oslo, who led one of the trials.

Among female participants in REBOOT, those taking beta-blockers - particularly those with good heart function receiving higher doses – had more adverse outcomes than women not taking the drugs, researchers reported in the European Heart Journal.

In REBOOT, researchers did see a lower rate of new heart attacks, heart failure, or death with beta-blocker use by patients with mildly reduced heart function, as indicated by a left ventricular “ejection fraction” between 40% and 49%.

The effect in this subgroup was confirmed in an analysis of data pooled from REBOOT, BETAMI–DANBLOCK, and a Japanese trial, according to a report published in The Lancet.

The message for cardiologists, Ibanez said, is “We can now state with confidence that beta-blockers are beneficial” in patients with mildly impaired heart function, and “there remains reasonable uncertainty about their benefit” in patients with normally functioning hearts.

Atar said an analysis looking specifically at beta-blocker use by patients with normal heart function will be presented at a U.S. cardiology meeting in November.

(Reporting by Nancy Lapid; editing by Caroline Humer and Diane Craft)

((Nancy.Lapid@thomsonreuters.com;))