乌鸦传媒

BASEL, Switzerland, Jan. 27 -- Heart failure therapy guided by the cardiac biomarker N-terminal brain natriuretic peptide (BNP) may not improve outcomes, particularly for older patients, researchers found.

Compared with conventional symptom-guided therapy, more aggressive treatment targeting both elevated N-terminal BNP levels and symptoms did not alter survival free of all-cause hospitalizations (41% versus 40%, P=0.39), Matthias Pfisterer, M.D., of the University Hospital Basel, and colleagues reported in the Jan. 28 issue of the Journal of the American Medical Association.

Although those in the 60 to 75 age group did appear to gain from treating elevated N-terminal BNP in the randomized controlled trial, those over 75 showed more adverse events with no benefits.

As they did when the findings were initially presented at the European Society of Cardiology meeting last year, the researchers cautioned that "it may not be beneficial to push doses to the limits" in elderly patients. (See: ESC: TIME-CHF Raise Questions About Aggressive Treatment in Oldest Patients)

Notably, N-terminal BNP-targeted therapy did not reduce the level of this biomarker more than symptom-guided therapy did.

"Thus, the value of BNP levels to guide therapy in addition to clinical symptom-based judgment seems limited despite their undisputed diagnostic and prognostic importance," the researchers concluded.

Nevertheless, it was reassuring that BNP-guided therapy appeared safe in patients younger than 75, commented Ileana L. Piña, M.D., of Case Western Reserve University in Cleveland, Ohio, and Christopher O'Connor, M.D., of Duke University in Durham, N.C., in an accompanying editorial.

"There are no easy answers and no simple solutions in the search for a single biomarker for diagnosis, prognosis, and treatment of heart failure," they wrote. "It may be the method of reduction of BNP levels that matters most in improving outcomes for patients with heart failure."

Dr. Pfisterer's group originally expected that N-terminal BNP-guided therapy would yield the greatest advantage in the oldest patients, "who are less physically active and in whom symptoms are less reliable."

So age was a prospectively defined subanalysis in their Trial of Intensified versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF).

This multicenter study included 499 patients with heart failure of New York Heart Association Class II or worse despite medical therapy, who had a left ventricular ejection fraction less than 45%, a heart failure hospitalization within the previous year, and an N-terminal BNP level at least twice the upper limit of normal.

The study included 289 patients 75 or older, which is a higher proportion of older patients than in most of the previous studies.

Participants were randomly assigned to uptitration of guideline-based treatments targeting symptoms alone or symptoms plus BNP levels.

Both groups were treated with ACE inhibitors or angiotensin-receptor blockers and beta-blockers. Patients with NYHA Class III or IV heart failure were also given spironolactone (Aldactone) or eplerenone (Inspra).

Over 18 months of follow-up, the BNP-guided group received more aggressive therapy (P
The intensified therapy did not, however, improve the primary outcome of 18-month survival free of all-cause hospitalizations compared with conventional therapy (41% versus 40%, hazard ratio 0.91, P=0.39).

For the primary quality of life outcome, both groups improved during the trial without a difference between treatment strategies.

Survival free of hospitalization for heart failure -- a secondary end point -- did improve with N-terminal BNP-guided therapy compared with symptom-guided therapy (72% versus 62%, HR 0.68, P=0.01).

When the analyses were stratified by age, those 60 to 75 had benefits not seen in those 75 years or older.

The results were as follows:

• Improved survival free of any hospitalization in the younger group only (HR 0.70, P=0.095, versus HR 1.10, P=0.54).
• Reduced overall mortality in the younger group only (HR 0.41, P=0.02, versus HR 0.88, P=0.61).
• Improved survival free of hospitalization for heart failure in the younger group only (HR 0.42, P=0.002, versus HR 0.87, P=0.45).

Although serious adverse events did not differ between groups overall, those in the older group had significantly more treatment-related serious adverse events with N-terminal BNP-guided therapy (10.5% versus 5.5%, P=0.12 and P=0.01 for interaction between age and treatment group).

The researchers cautioned, though, that the trial was powered for the overall cohort, not the age-based subgroup analyses.