麻豆传媒

Against expectations, critically ill people in cardiogenic shock fared similarly receiving one widely used inotrope or another in the small DOREMI trial.

Patients had the same clinical outcomes on milrinone and dobutamine in terms of the study's primary composite outcome (RR 0.90, 95% CI 0.69-1.19) and its individual endpoint components:

• In-hospital death: 37% vs 43% (RR 0.85, 95% CI 0.60-1.21)
• Resuscitated cardiac arrest: 7% vs 9% (HR 0.78, 95% CI 0.29-2.07)
• Receipt of mechanical circulatory support or cardiac transplant: 12% vs 15% (HR 0.78, 95% CI 0.36-1.71)
• Nonfatal myocardial infarction: 1% vs 0%
• Stroke or transient ischemic attack: 1% vs 2% (HR 0.50, 95% CI 0.05-5.50)
• Initiation of renal replacement therapy: 22% vs 17% (HR 1.39, 95% CI 0.73-2.67)

"Moreover, we did not identify any significant between-group differences in safety outcomes or in surrogate markers of resuscitation, including heart rate, blood pressure, and serum lactate level," reported Benjamin Hibbert, MD, PhD, of the University of Ottawa Heart Institute, Ontario, and colleagues in the .

Study authors "have nicely demonstrated that no significant differences are present with the use of dobutamine and milrinone, an important and useful finding," commented Babar Basir, DO, of Henry Ford Health System in Detroit.

Milrinone and dobutamine, both inotropes that can also be classified as vasodilators, are widely used in the early management in cardiogenic shock to maintain end organ perfusion.

In current practice, their differing mechanisms of action -- milrinone being a PDE3 inhibitor and dobutamine a synthetic catecholamine acting as a beta-adrenoceptor agonist -- are often weighed in lieu of robust comparative data on inotrope selection.

"Many clinicians have felt use of these medications was part of the 'art' of medicine. Clinicians would create specialized cocktails of medications to help the specific needs of their patient based on the presence of arrhythmias, right ventricular involvement, and renal function," Basir said.

Anecdotally, clinicians tend to favor milrinone over dobutamine, commented Claudia Gidea, MD, of NYU Langone Health in New York City.

"The cardiology community needs more of these randomized, blinded clinical trials in order to have a better understanding of the inotropic therapy we can offer to patients in classic cardiogenic shock and [to] avoid practice preferences or anecdotal beliefs that one inotrope is better than the other," she said.

recruited a broad range of critically ill patients, all from the same center, in the phases of shock that are typically treated with inotropes. The double-blind trial had 192 patients randomized to milrinone or dobutamine infusion.

The two groups shared similar baseline characteristics. Mean age was around 70, and over one in three were women. Approximately two-thirds of patients had ischemic cardiomyopathy.

Basir noted that with a mortality rate around 40%, DOREMI reaffirms the poor prognosis of cardiogenic shock patients.

"Future studies focusing on earlier intervention (i.e., with patients in class B or 'beginning' cardiogenic shock) may identify therapies capable of altering the natural history of cardiogenic shock -- a goal that may be difficult to achieve after hypoperfusion and end organ dysfunction occurs," according to Hibbert's group.

The power calculation for the study had been based on the expectation of a large treatment effect, so the trial was ultimately underpowered to detect smaller between-group differences, Hibbert and colleagues acknowledged.

They added that study groups could have had different outcomes beyond the index hospitalization that were not captured in DOREMI. Furthermore, recruitment at a single center may limit the study's external generalizability, they cautioned.

For now, "I think the results will certainly inform clinical practice, but may not change clinical practice," said Sean van Diepen, MD, of University of Alberta, Edmonton, who was not involved with DOREMI.

"I suspect many clinicians will continue to tailor their inotrope choices based on the patient's hemodynamic profile and the somewhat different chronotropic and vasodilatory properties of the two drugs," he commented.

"It clearly sets the stage for a future larger multicenter trial," van Diepen said of DOREMI.

Unanswered questions in the field include whether an inotrope should be routinely used in cardiogenic shock and whether mechanical circulatory support may improve outcomes.

Comment