No difference between treatment with milrinone, dobutamine in cardiogenic shock

Reuters Health - 04/08/2021 - Milrinone and dobutamine are equally effective in helping to stabilize patients whose lives are threatened by cardiogenic shock, according to a new pragmatic test in 192 patients.

The results, published in The New England Journal of Medicine, show that the combined risk of in-hospital death from any cause, resuscitated cardiac arrest, heart attack, stroke or other serious outcomes associated with the loss of blood to vital organs was 49% with milrinone and 54% with dobutamine (P=0.47).

When the research team, led by Dr. Benjamin Hibbert of the University of Ottawa Heart Institute, in Canada, looked at individual outcomes, they also found the two well-established drugs to be comparable.

The death rates, for example, were 37% with milrinone and 43% with dobutamine.

"This is the only randomized study of cardiogenic shock to compare these two treatments," Dr. Hibbert told Reuters Health by phone. "This is the most lethal condition we have in cardiology and we don't have a good evidence base for a lot of the therapeutics we have."

Nearly half of cardiac patients who present with cardiogenic shock die.

In the United States, milrinone is ten to twenty times more expensive than dobutamine and it tends to be more popular because many doctors have the impression that it is the superior inotrope.

The new study, known as DOREMI, "deflates one of the commonly held myths that we should be using milrinone because it's better. That was our hypothesis when we started the study and it often got selected despite its increased costs," said Dr. Hibbert, an interventional cardiologist and director of the Vascular Biology and Experimental Medicine Laboratory.

Although the two treatments have different hemodynamic profiles, "a lot of the observations about physiological effects are derived from animal data or response to therapy in healthy people," he said. "But a lot of the reported differences in hemodynamic profiles we really didn't observe when we used the drugs as they were intended to be used in the sickest patients."

All were treated at the University of Ottawa Heart Institute from 2017 to 2020 and randomization was stratified based on the affected ventricle. Most were experiencing classic or deteriorating cardiogenic shock. Drug dosing was based on physician preference rather than any standardized protocol.

"There was no evidence of heterogeneity of the treatment effect across the prespecified subgroups, including those defined according to sex, age, affected ventricle, cause or severity of left ventricular dysfunction, severity of baseline renal dysfunction, or concomitant use of vasopressors at time of inotrope initiation," the researchers write.

Renal-replacement therapy was required in 22% getting milrinone versus 17% who received dobutamine.

Rates of mechanical circulatory support were 12% and 15% respectively.

Seven percent treated with milrinone had a resuscitated cardiac arrest compared to 9% who were given dobutamine.

The rates of stroke or a transient ischemic attack were 1% and 2% respectively.

Length of stay in the intensive-care unit or in the hospital as a whole was not affected by the drug prescribed. Neither was the duration of inotropic therapy.

The research team also found that the drug prescribed did not make a difference in heart rate, blood pressure, serum lactate level, urine output or other measures.

The team is undertaking a follow-up study that includes a placebo.

"We don't know if this class of drugs is even necessary," said Dr. Hibbert. "We're going to see if we even need them, or if they're harmful in this cohort of patients."

The impact of the DOREMI results may also extend to tests of mechanical circulatory support for cardiogenic shock.

In such studies, "if there are important differences in your medical-therapy arm, that can lead to problems," he said. "The fact that we know there's no difference in the two main approved therapies means that, from a medical-therapy standpoint, you won't confound your other studies of cardiogenic shock."

The study did not have commercial funding.

SOURCE: https://bit.ly/2V9TwoL The New England Journal of Medicine, online Aug. 4, 2021

By Gene Emery

 



Posted on 4 August 202117 August 2021