高齢者に対する集中治療は有益でない

TIME-CHF:心不全の高齢患者に対する集中治療は有益でない
TIME-CHF: Elderly patients with heart failure do not benefit from intensive medical therapy
TIME-CHF:Trial of Intensified (BNP-guided) versus standard(symptom-guided)Medical therapy in Elderly patients with Congestive Heart Failure(うっ血性心不全の高齢患者に対する集中治療[BNPを指標にする]対標準[症状を指標にする])スタディにおいて、心不全の管理に症状のみでなくナトリウム利尿ペプチドレベルを使用しても死亡およびあらゆる原因による入院を減少させることができなかった、と2008年European Society of Cardiology学会で発表された。しかし、結果は年代により有意に異なった。収縮能低下による心不全(駆出率≤45%)の患者499人をN末端脳型ナトリウム利尿ペプチド(NT-BNP)を指標にする群または症状を指標にする群に無作為に割り付け、75歳以上対60~74歳の群に層別化した。標準的な治療と比較しNT-BNPを指標とした集中治療は、一次エンドポイントである無入院生存期間を改善しなかった(ハザード比[HR]0.92、p=0.46)が、より疾患特異的なエンドポイントである心不全による入院のない生存期間は改善した(HR=0.66、p=0.008)。若年群においてNT-BNPを指標とした集中治療により全死亡率は低下し(HR=0.38、p=0.01)心不全による入院のない生存期間は改善した(HR=0.41、p=0.002)が、75歳以上の群においてはこれらの変化は認められなかった。これらの結果から、若年患者の結果に基づいた一般的な勧告は後期高齢患者には必ずしも直接当てはめることはできない可能性のあることが示唆された。
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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 hospitalizations. However, the response to this intervention differed significantly between patients aged 60-74 years and those aged ≥75 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.

The 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 ≥60 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 it 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 ≥75 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 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 hospitalizations 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 hospitalization 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 hospitalizations, but not all-cause hospitalizations. This 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 hospitalized or die due to reasons other than heart failure. This might explain why death and hospitalization 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.

The 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.