AHA 2008: MR-proADM Better Prognostic Tool Than BNP, But Not Everybody Convinced of Biomarker's Merit

November 11, 2008

November 11, 2008 (New Orleans, Louisiana) — A novel biomarker of vascular status is a better predictor of mortality at three months than brain natriuretic peptide (BNP) in acute heart-failure patients presenting at the emergency department with shortness of breath. The use of mid-region pro-adrenomedullin (MR-proADM) was also a better predictor of mortality than N-terminal pro-BNP (NT-proBNP), and these data suggest that MR-proADM can help triage very high-risk heart-failure patients who should be treated intensively.

"This new biomarker is superior to the best existing prognostic tool we have," lead investigator Dr Stefan Anker (Charité University Medical School, Berlin, Germany) told heartwire . "I can tell you that emergency-room physicians want to triage patients. We believe that using it would result in fewer patients being admitted to the hospital and would also get patients out of the hospital more quickly. Using this new biomarker would be cost-effective and save the healthcare system money."

You can't use this to put someone to the front of the line, because everyone is already at the front of the line.

Presenting the results of the Biomarkers in the Assessment of Congestive Heart Failure (BACH) trial here at the American Heart Association 2008 Scientific Sessions, Anker said the routine assessment of MR-proADM "can help identify patients who should move to the front of the line of medical care."

During a morning press conference, however, Dr Milton Packer (University of Texas Southwestern, Dallas, TX), the scheduled discussant during the late-breaking clinical-trials session, challenged the interpretation of the BACH investigators.

"We give every patient that comes into the emergency room optimal medical care, whether or not the prognosis indicates a high risk of death or a very high risk of death," Packer told the media. "Both of those [types of patients] get optimal medical therapy. The truth is you can't use this to put someone to the front of the line, because everyone is already at the front of the line. . . . This marker doesn't add very much to existing biomarkers, and it doesn't change our clinical management of patients."

Improving Prognostic Power in Acute Heart Failure

During his presentation, Anker said that ADM is a peptide hormone that acts as a vasodilator and plays important roles in microcirculation and endothelial dysfunction. MR-proADM is a stable and surrogate marker for ADM release, something that occurs in endothelium dysfunction.

In this study, the BACH researchers wanted to test whether measuring MR-proADM is better than BNP in predicting 90-day mortality in patients who presented to the emergency department with shortness of breath. In total, 1641 patients were enrolled in the study, of whom 568 were diagnosed with acute heart failure. Patients were 64 years old and had a range of comorbidities, including 36% with a history of heart failure, 19% with prior acute MI, and 29% with diabetes mellitus.

At 90 days, the prognostic accuracy of MR-proADM was 73.5% compared with 60.8% for the measurement of BNP levels (p<0.001). In terms of secondary end points, the BACH researchers showed that MR-proADM was also a better predictor of 90-day mortality than NT-proBNP. In an analysis of MR-proADM by quartiles, patients with the highest levels, those with MR-proADM measurements >2.07 pmol/L, had a threefold higher risk of dying at 90 days than those in the lowest three quartiles.

Debating the Merits of MR-Proadm

Commenting on the findings, Packer noted that BNP isn't a particularly good biomarker for heart-failure prognosis and that physicians do best when assessing and predicting prognosis based on routine clinical assessment. He also questioned whether there was a need for MR-proADM, especially since knowing the patient's level is not going to change clinical care.

It is important to know that this particular patient might have outcomes that aren't quite as encouraging.

"The emergency-room physician is in charge of making a diagnosis and not with making a prognosis," said Packer. "The management of these patients is not changed one iota if you categorize them as very high risk or high risk . . . but, assuming the emergency-room physician didn't know that, and he wanted to use this test as a triage and would give optimal medical therapy only to patients with a high value. Here is my proposal: draw the test, send it to the lab, suppress the value and send back a very high value in everyone so that everyone would get optimal medical care. The truth is that if this is a mechanism of triage for medical care, I would personally like to see all of my patients have high value. Otherwise, it makes no sense."

Dr Clyde Yancy (University of Texas Southwestern, Dallas, TX) said the MR-proADM test presents an opportunity to more precisely diagnose patients, particularly when the initial presentation is ambiguous. "It also helps us understand who is at high risk," he said. "There is some importance in knowing who is at high risk, regardless of whether you can change therapy. It is important to know that this particular patient might have outcomes that aren't quite as encouraging."

Like Packer, Yancy said the stumbling block with these tests is how the new information is applied. "If you don't have a treatment strategy that would be exclusive for the patient at high risk, then one could argue that identifying risk per se doesn't help you."

Referring to Packer, Anker said: "I wish he were right in that all people would be as good at assessing the prognosis based on their clinical judgment and biomarkers as he would probably be in the emergency room." Physicians need biomarkers to aid their clinical judgment, he added, something that has been recognized by medical societies and the Food and Drug Administration and that has allowed for studies and the development of various tests, including the gold standard BNP.

Brahms AG sponsored the BACH study. Anker reports consulting and research support from Brahms AG.

face="Verdana" size="1">The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.


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