Cardiac Biomarker ST2 Proves Far Superior To Galectin-3 In A Head-to-Head Study

  Cardiac Biomarker ST2 Proves Far Superior To Galectin-3 In A Head-to-Head
  Study

Galectin-3 pales in comparison. ST2 provides the most accurate risk prediction
for patients with heart failure, even improving discrimination when the two
most-popular cardiac biomarkers, natriuretic peptides and high-sensitive
troponin, are included.

Business Wire

SAN DIEGO -- September 30, 2013

Critical Diagnostics announced today that the study, “Head-to-head comparison
of two myocardial fibrosis biomarkers for long-term heart failure risk
stratification: ST2 vs. Galectin-3”, recently published online in JACC (the
Journal of the American College of Cardiology) comparing the company’s novel
cardiac biomarker ST2 to Galectin-3 (Gal-3), a biomarker from BG Medicine
(NASDAQ: BGMD), found ST2 to be superior.

Study investigators followed 876 heart failure patients over a 5-year period,
comparing ST2 and Gal-3’s ability to predict all-cause death and
cardiovascular mortality over conventional clinical assessment, using 11
standard risk factors (age, sex, NYHA functional class, estimated glomerular
filtration rate, left ventricular ejection fraction, diabetes mellitus,
sodium, hemoglobin, ischemic etiology of HF, ACE inhibitor or ARB drug
treatment, and beta-blocker treatment) plus NT-proBNP.

In a rigorous multivariate analysis, only ST2 remained independently
associated with all-cause and cardiovascular mortality. The incremental
predictive contribution of Gal-3 to existing clinical risk factors was, as the
study authors pronounced, “trivial,” and when troponin was included, Gal-3
fell out of the model.

The same study also showed that ST2 adds considerable prognostic value even
when the commonly used biomarkers for heart failure patient care, Roche
Diagnostic’s (OTC: RHHBY) NT-proBNP, as well as high-sensitive troponin are
also considered.

“This study emphasizes the clinical value of the emerging biomarkers of
cardiac fibrosis for risk assessment in patients with ambulatory heart failure
and establishes finally and unequivocally that ST2 is superior to Gal-3 for
this clinical objective”, states James Snider, President of Critical
Diagnostics. “As the study showed, every 10 ng/mL increase in ST2 increased a
patient’s risk by 20 percent. For example, a patient with an ST2 level of 85
ng/ml is at a two-fold higher risk, than a patient with an ST2 level at the
FDA cleared threshold of 35 ng/ml. At 135 ng/mL, that patient would be at a
three-fold higher risk. That’s pretty straightforward and offers physicians a
simple metric to utilize ST2 in risk assessment of their patients for
determination of the best course of treatment.”

Note the authors: “This study highlights the importance of assessing the true
value of emerging cardiac fibrosis biomarkers above and beyond clinical risk
factors and natriuretic peptides particularly in light of the newly obtained
ST2 . . . ACC/AHA class II recommendation for determination of prognosis in
chronic HF. ST2 significantly refined discrimination and reclassification
analysis while Gal-3 had negligible effects on performance metrics in risk
prediction models.”

“In all studied cohorts with or without additional biomarkers, including
natriuretic peptides, ST2 unambiguously emerged as a cardinal HF risk
stratifier . . . these main findings suggest that the pathways identified by
ST2 profoundly affect risk stratification in the context of chronic HF . . .
The incorporation of ST2 into clinical practice for the prediction of
all-cause and cardiovascular mortality should be readily contemplated by the
practicing clinician.”

“As the body of evidence grows for ST2, Gal-3’s limitations become more
glaringly apparent,” remarks Snider. “For instance, not only is Gal-3 shown to
be an inferior risk predictor, additionally, elevated Gal-3 levels tend to
remain high, regardless of any change in a patient’s condition.”

The authors point to a recent transplant study in which serum Gal-3 levels
were measured before and after a heart transplant. Gal-3 levels stayed
elevated even after patients received new hearts, leading the authors to
conclude that Gal-3 is a systemic biomarker rather than being specific to
heart disease. By comparison, ST2 has been shown to be directly involved in
cardiac fibrosis, and ST2 levels change rapidly with changes in a patient’s
condition, which makes ST2 an excellent biomarker for assessing patient status
with serial testing.

“We also know that Gal-3 levels are affected by common confounders, such as
renal function, greatly compromising its clinical utility in heart failure
patients,” notes Snider. “ST2 is not affected by renal function or, for that
matter, many of the most common confounders such as age or body mass index.
Another big differentiator is that ST2 has a single cutpoint. If a patient’s
ST2 level is above 35 nanograms per milliliter, they are considered at risk.
Gal-3, on the other hand, has multiple cutpoints, so decision-making can
become confused and problematic.

“As if all that were not enough, the performance of a biomarker is dependent,
in part, on both its analytical and biological variability in clinical use. A
biomarker’s Reference Change Value (RCV) reflects both of these measurements,
expressed as the change in the value needed to indicate clinically meaningful
change in a patient’s condition. Biomarkers with lower RCV values require less
change to be significant. This is obviously important when serially monitoring
patients. In a seminal study published this year (‘Biological variation of
galectin-3 and soluble ST2 for chronic heart failure: Implication on
interpretation of test results’) by Alan H.B. Wu, Ph.D., Professor of
Laboratory Medicine at UCSF, and Chief of the Clinical Chemistry Laboratory at
San Francisco General Hospital, ST2 was shown to have an RCV less than half
that for galectin-3, making it doubly powerful.”

“It’s easy to see why, given the overwhelming body of evidence from the
scientific community, more and more clinicians are turning to ST2 to help
assess risk and guide treatment of their heart failure patients,” says David
Geliebter, CEO of Critical Diagnostics. “This study hopefully puts an end to
any debate on that issue. In a fully adjusted model, Gal-3 added no value over
the standard risk factors and current biomarkers. What’s more, alarmingly, in
this most recent study, Gal-3 wrongly reclassified patients into a lower risk
category who eventually died.

“We are happy to say that the real winners in all this are the millions of
people living with heart failure,” adds Geliebter, “because it means they will
have a better chance to live happier, healthier, longer lives thanks to ST2.”

About ST2

ST2 is a soluble protein expressed by the heart in response to disease or
injury. It is reflective of ventricular remodeling and cardiac fibrosis. ST2
is not adversely affected by confounding factors such as age, body mass index
and impaired renal function. Unlike many other cardiac biomarkers, ST2 levels
change quickly in response to changes in the patient’s condition—thus helping
physicians make informed decisions on an appropriate course of action to take
and, if needed, to quickly adjust treatment. All this makes ST2 an ideal
serial biomarker for monitoring and treating heart failure patients.

The Presage® ST2 Assay from Critical Diagnostics is the only commercially
available ST2 biomarker in the world. The Presage ST2 Assay has been CE Marked
and cleared by the U.S. FDA for use as in the risk stratification of chronic
heart failure patients.

ST2 is included in the 2013 ACC/AHA Guideline For The Management of Heart
Failure, which calls ST2 “not only predictive of hospitalization and death in
patients with HF [heart failure] but also additive to natriuretic peptide
levels in [its] prognostic value.” The guideline gives ST2 its highest
classification (“A”) for the body of evidence supporting its recommendation.

About Critical Diagnostics

Founded in 2004, Critical Diagnostics (www.criticaldiagnostics.com) develops
novel biomarkers to help physicians optimize patient care in cardiovascular
diseases, while containing healthcare costs. Critical Diagnostics has
distribution partners for its Presage ST2 Assay in 45 countries, covering
two-thirds of the world’s population.

Contact:

Dennis Dalangin, 877-700-1250
VP Marketing
ddalangin@criticaldiagnostics.com