SAN DIEGO--(EON: Enhanced Online News)--Critical Diagnostics announced today that results of a post-hoc analysis of a previously described prospective, randomized, controlled study of well treated heart failure patients showed that patients, at baseline above the FDA-cleared threshold of 35 ng/mL for the company’s cardiac biomarker ST2, who were taking low doses of beta blocker were almost seven times as likely to experience a cardiovascular event, such as an unplanned hospitalization, than patients who had low ST2 levels and were on high-doses of beta blocker.
“At the end of the day, the real-world test of a biomarker is that it show true clinical value”
The study (“Soluble Concentrations of the Interleukin Receptor Family Member ST2 and Beta Blocker Therapy in Chronic Heart Failure”), recently published online by the American Heart Association’s journal Circulation: Heart Failure, furthermore proved that patients above the FDA-cleared ST2 threshold of 35 ng/mL, who were taking low doses of beta blocker were almost three times as likely to experience a cardiovascular event as those who were also above the FDA-cleared ST2 threshold, but on high-doses of beta blockers.
Beta blockers are used by tens of millions of Americans to treat high blood pressure and other heart ailments, such as heart failure, yet despite their proven benefit and vigorous support in clinical practice guidelines, the actual dose of beta blocker achieved in standard practice is considerably lower than the guideline-recommended dose due to potential side effects, the cost of medication, and poor understanding of whether higher doses of beta blocker are providing added benefit to a particular patient.
The authors of the study had previously demonstrated that change in beta blocker dose in heart failure patients was directly associated with a change in subsequent levels of ST2 and that ST2 was also associated with change in ventricular remodeling, leading them to investigate whether ST2 could be used to identify patients who would benefit from higher beta blocker doses in this Massachusetts General Hospital study of 151 subjects with heart failure due to left ventricular systolic dysfunction.
Subjects were followed over a 10 month period. A multivariable model was created with both baseline ST2 levels and final achieved beta blocker dose. Model variables included age, gender, ischemic cardiomyopathy, atrial fibrillation or flutter, NYHA class III or IV, baseline heart rate, baseline NT-proBNP and baseline eGFR (estimated glomerular filtration rate). When all clinical and laboratory characteristics were included into a model predictive of CV events, the only biomarker independently predictive of cardiovascular events was ST2.
“Our proof-of-concept analysis suggests that biomarker concentrations may identify a risk that may theoretically be mitigated by specific drug therapy, raising the possibility that higher dose BB [beta blocker] therapy may be particularly efficacious in the face of an elevated sST2,” note the authors, adding, “Another hypothesis-generating inference from this data may be that a low sST2 value may be protective against CV [cardiovascular] events in patients with other poor prognostic markers such as low achieved BB dose or high baseline NT-proBNP values.”
“At the end of the day, the real-world test of a biomarker is that it show true clinical value,” says David Geliebter, CEO of Critical Diagnostics. “You need to see a treatment interaction for a biomarker to be meaningful. As this study shows, ST2 delivers on this promise, providing physicians with important evidence to assess disease status, above and beyond clinical observations, with which to deliver more efficient and effective, yet tailored, care to the millions of people suffering from heart failure.”
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 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.