TIME-CHF Trial: Elderly HF patients do not benefit from intensive medical therapy

Intensified, BNP-guided therapy was no more effective than a standard, symptom-guided approach in elderly heart failure patients in reducing the number of deaths and all-cause hospitalisations. However, the response to this intervention differed significantly between patients aged 60-74 years and those aged ¡Ý75 years. This indicates the need for specific data in this large subset of very old heart failure patients who have been largely excluded from large treatment trials.

Our study was carried out in 15 hospitals in Switzerland and Germany and included 499 heart failure patients with reduced pump function of the heart aged ¡Ý60 years. The study was called TIME-CHF, standing for the Trial of Intensified (BNP-guided) versus standard (symptom-guided) Medical therapy in Elderly patients with Congestive Heart Failure. Patients in both groups were well treated according to current guidelines, but doses of medication were significantly increased in the BNP-guided group. Increase in medication took place within the first 6 months after study inclusion and patients were followed up for another 12 months. This study has several aspects that may be relevant for the treatment of heart failure patients, particularly since we included a population that is representative for patients as seen in daily practice. Patients were on average 77 years old (82 years in the group aged ¡Ý75 years) and had many diseases other than heart failure, i.e. app. 80% had 2 or more additional diseases. Previous studies had largely excluded such patients.

Symptoms and quality of life of patients in both intervention groups improved with treatment, irrespective of age. Death rate in all patients was lower than we expected. This indicates that all patients with heart failure seem to profit from current standard therapy. With more intensified therapy, younger patients showed lower death rate and less hospitalisations due to cardiac reasons, including heart failure, than with standard therapy. However, this was not the case in older patients, where patients with intensified therapy had similar death and hospitalisation rate, but worse quality of life than with standard treatment. Therefore, general treatment recommendations which are based on results in younger patients, may not necessarily be directly applicable to very old patients. This particularly applies to patients with relevant diseases other than heart failure. Studies testing interventions in these very old patients, such as TIME-CHF, are needed to define the best therapies. In addition, it may not be beneficial to push doses to the limits in the very elderly and in those with other relevant health problems.

The intervention reduced the disease specific endpoint of death and heart failure hospitalisations, but not all-cause hospitalisations. The latter is more relevant for patients, which is why we used this as our primary outcome measure. In previous studies, however, disease specific endpoints have been used. Our study indicates that the net benefit of treatment might be smaller than expected from the large treatment trials, particularly in patients who are likely to be hospitalised or die due to reasons other than heart failure. This might explain why death and hospitalisation rates in the general heart failure community over the last two decades decreased at a lesser rate than was expected based on results from studies. In addition, TIME-CHF shows how important it is to study patients as seen in daily practice since the conclusion may not be exactly the same.

Our findings need to be confirmed before it can be generally recommended to use different therapies in heart failure patients depending on their age. Nevertheless, it may help to better define individual needs for heart failure patients and to boost the urgently needed studies in this large heart failure population of very old patients.