TIME-CHF trial: intensified heart failure therapy does not improve survival free of all-cause hospitalisations in older patients

It is uncertain whether intensified, NT-BNP-guided therapy of heart failure improves outcome compared to standard, symptom-guided therapy, and whether there is a difference in the response in patients ≥ versus < 75 years of age.

Therefore, 499 patients with systolic heart failure ( ejection fraction less than or equal to 45% ) were randomised to an NT-BNP-guided or a symptom-guided strategy and stratified into patients aged ≥ 75 versus 60-74 years.
Included were patients with dyspnea NYHA ≥ II, heart failure hospitalizations within one year and NT-BNP levels > 400 pg/ml ( 60-74 years ) or 800 pg/ml ( ≥ 75years ).
Therapy was uptitrated according to guidelines aiming to reduce symptoms to NYHA £ II or additionally NT-BNP-levels below levels mentioned above.

The primary endpoint was survival free of all-cause hospitalisations up to 18 months and quality of life. Secondary endpoints were survival and heart failure hospitalization-free survival.

Compared to standard therapy, intensified treatment did not improve primary endpoint ( hazard ratio, HR=0.92, p=0.46 ), but did improve the more disease-specific endpoint of survival free of heart failure hospitalisations ( HR=0.66, p=0.008 ).

Intensified therapy reduced total mortality ( HR=0.38, p=0.01 ) and improved survival free of heart failure hospitalisations ( HR=0.41, p=0.002 ) in younger patients, but not in those ≥ 75 years.

In addition, quality of life improved less by intensified versus standard therapy in older patients despite similar reductions in symptoms and BNP-levels.

In conclusion, intensified heart failure therapy did not improve overall outcome compared to standard treatment. However, it improved survival free of heart failure hospitalizations overall and it reduced mortality in patients < 75 years of age, without similar benefits in older patients.

Source: ESC Congress, 2008


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