Biomarker Levels May Be Key to Heart Failure Decline
By Chris Kaiser, Cardiology Editor,
October 18, 2011
Action Points
Note that current treatment of chronic CHF due to left ventricular systolic dysfunction consists of the use of beta-adrenergic blockers and vasodilators, with the addition of aldosterone blockade or cardiac resynchronization therapy for those with persistent symptoms. Therapy is guided by ascertainment of clinical stability and volume status.
Note also that persistently elevated levels of NT-proBNP have been shown to be predictive of poor outcomes.
Point out that this study demonstrates that biomonitoring of NP-proBNP levels in combination with aggressive treatment based upon results can lead to significantly improved outcomes in patients with CHF.
Review
Monitoring levels of amino-terminal pro–B-type natriuretic peptide (NT-proBNP) and keeping them below a certain threshold proved to be more beneficial for heart failure patients than the standard of care, the PROTECT study found.
Those in the NT-proBNP monitoring arm had significantly fewer cardiovascular events (58 versus 100, P=0.009) at a mean follow-up of 10 months, James L. Januzzi Jr., MD, from Massachusetts General Hospital in Boston, and colleagues reported.
In addition, patients in the biomarker-monitored arm had fewer events per patient (0.77 versus 1.3, P=0.03) and a longer duration before their first event, according to the study in the Oct. 25 Journal of the American College of Cardiology.
At an interim analysis of the 151 patients thus far enrolled in PROTECT (75 in the NT-proBNP arm), the recommendation was made to stop enrollment because of a statistically significant reduction in the primary endpoint of total cardiovascular events favoring the NT-proBNP arm.
"We found a remarkable reduction in heart failure complications, primarily driven by improvements in worsening heart failure [27 versus 54, P=0.001] and reduced heart failure hospitalizations [11 versus 27, P=0.002]," Januzzi told MedPage Today in an interview.
"NT-proBNP levels are powerfully prognostic and allow therapeutic changes in those at highest risk. This is a very necessary step toward personalized healthcare in the heart failure space," Januzzi said.
The standard drug therapy for patients with chronic heart failure due to left ventricular systolic dysfunction (ejection fraction ≤40%) includes beta-adrenergic blockers and vasodilators, with the addition of an aldosterone blockade or cardiac resynchronization therapy reserved for those with persistent symptoms, Januzzi and colleagues wrote.
They also noted that "ascertainment of clinical stability and volume status in chronic heart failure can be challenging in inexperienced hands," and managing medication dosage is often suboptimal.
With that background, the investigators initiated the PROTECT (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting) study, a single-center randomized controlled trial.
The goal in the interventional arm was to lower NT-proBNP levels to 1,000 pg/mL or below and sustain them there.
The primary clinical endpoint was total cardiovascular events, which was a composite of worsening heart failure, hospitalization for heart failure, clinically significant ventricular arrhythmia, acute coronary syndromes, cerebral ischemia, and cardiac death.
The mean age of patients was 63 years, with 21% older than 75. The older patients averaged slightly more clinic visits than the younger patients (7.5 versus 5.0), and those in the NT-proBNP arm averaged one more clinic visit than those in the standard-of-care arm (6.0 versus 5.0).
Investigators saw a similar average therapy adjustment between the two arms (7 versus 6), but noted that those in the interventional arm had more aggressive dosing changes.
Levels of the biomarker were similar at baseline between the two arms, but declined significantly by the end of the study for those in the NT-proBNP arm (2,344 to 1,125 pg/mL, P=0.01) compared with the standard of care (1,946 to 1,844 pg/mL, P=0.61).
Researchers found a linear relationship between the levels of NT-proBNP and events. Those below 1,000 pg/mL had the lowest mean frequency of events (0.45 events) compared with those between 1,000 and 2,000 pg/mL (1.1 events), between 2,000 and 3,000 pg/mL (1.25 events), and above 3,000 pg/mL (2.0 events) (P<0.001 for trend).
Those in the interventional arm also reported higher quality of life scores. "Not only did they have fewer events, but they also felt better and had favorable reverse cardiac remodeling as seen with echocardiography," Januzzi said.
In an accompanying editorial, Alan Maisel, MD, from the VA San Diego Healthcare System, wrote that PROTECT proves that lowering NT-proBNP levels is "indeed possible, is safe (the kidneys still work, the blood pressure is fine), and may lead to more benefits compared with simple non-biomonitored up-titration of therapies."
Despite the study being single-center and unblinded, it had "strong adherence to study protocol with consistent biomonitoring of NT-proBNP levels, allowing aggressive therapeutic efforts at NT-proBNP lowering," Maisel said.
Because of the relatively small sample size, brief duration of follow-up, and rigorous protocols, these results must be proven in a real-world setting, Maisel said.
In fact, Januzzi said the researchers are readying for a larger multicenter randomized trial. In addition, he and others are researching home-based finger-prick NT-proBNP testing.