Michael Fu， MD， PhD， FESC
Head， Heart Failure Center Medicine， Sahlgrenska University Hospital/Sahlgrenska， SE 413 45 Gothenburg， Sweden
 
Chronic heart failure accompanied by higher comorbidity and mortality is increasing in line with advancing age. Previous landmark randomised clinical trials were mostly conducted in younger systolic heart failure patients with an average age of < 63 years and a left ventricular ejection fraction of < 40%. However， in “real world” clinical practice， the majority of patients with chronic heart failure are older and the median age at presentation of new heart failure cases is often > 75 years. Such cases are less often treated by heart failure specialists， are more symptomatic， and almost half have preserved systolic function. This lack of a representative sample of elderly patients in previous clinical trials has raised serious concerns about extrapolating the available evidence from a younger to an elderly heart failure population.
 
Does age really make a big difference in heart failure management?
 
Yes， physiologically and pathologically as well as epidemiologically. There are age-dependent structural and functional changes in elderly patients， particularly those with heart failure. Age-dependent changes include， for example， increases in sympathetic activity， left ventricular wall diameter， myocardial fibrosis and apoptosis as well as coronary sclerosis and aortic stiffness. As a consequence， both systolic and diastolic dysfunctions are more frequent in older patients than younger ones. Moreover， there is an obvious shift in phenotype from systolic to diastolic heart failure in elderly patients， especially in those with hypertension and/or diabetes and in female patients. Hypertension is a more predominant cause of heart failure in the elderly compared to younger patients. Both morbidity and mortality are increased by systolic or diastolic heart failure or both. A physiological decrease in cognitive， lung and renal function is more frequent in older patients compared to their younger counterparts. Therefore， older patients may respond differently to drugs， both in terms of efficacy and tolerability， which makes it important to be able to recognize the biological， pharmacological and functional differences associated with advanced age.
 
How should we manage chronic heart failure in the elderly in view of the above mentioned biological difference? Should we follow the same guidelines (based on studies of younger heart failure patients) as for a younger age group?
 
There is evidence available about beta blocker therapy in the elderly patients with heart failure. A prospective Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (SENIORS) and a subgroup analysis of landmark clinical trial MERIT-HF  in stable systolic heart failure have provided data supporting the use of beta blocker as baseline therapy in heart failure in the elderly. Therefore we are obliged to stick to available CHF guidelines regardless of their ages in terms of use of beta blockers. 
 
What do we do in our daily clinical practice? 
 
For the first， beta blocker is still less frequently used， particularly in the elderly.
There are many reasons， one of which is that there is a lack of consensus about whether beta blockers are equally beneficial and well tolerated in elderly heart failure patients as in younger ones.  This may be due to the fact that the level of evidence regarding beta blocker therapy in the elderly in general is not regarded to be as high as that in younger patients， despite that beta blocker is hitherto best documented as compared to other therapies such as ACE inhibitor in aged heart failure patients. As we know， only three beta blockers (bisoprolol， carvediolol and metoprolol succinate) are recommended for patients < 65 years with systolic heart failure. However in the elderly Nebivolol and Metoprolol succinate are probably mostly studied. In our own heart failure clinic， the average prescription of beta-blocker (mostly metoprolol CR/XL) in heart failure in the elderly (median age around 80 years) is 82% of patients， half of whom achieved 50% of the target dose.
 
For the second， the dosage of beta blocker is far away from optimal， particularly in the elderly.
The issue of target doses is frequently discussed， since they are in many cases difficult to achieve in the elderly. The question is whether we should use the same target dose in the elderly as that in younger patients. Theoretically， the most effective dose is the highest dose tolerated， which may differ across different age groups. Is it wise to adopt “the highest dose tolerated” instead of “the target dose”? While it is probably reasonable to adopt “the highest dose tolerated”， it certainly requires further investigation. Although in many patients the highest doses tolerated are actually same as the recommended target dose， it does not fit well with all patients， particular in the elderly. Moreover， in order to reach the highest tolerable dose it necessitates a sense of patience， responsibility and care. But it is worthwhile since your little time will give your CHF patients longer time to live.
 
How can we ensure that the highest dose tolerated is achieved? There are many ways to do this， one of which is brain natriuretic peptide (BNP)-guided strategy. Elderly heart failure patients have more non-specific symptoms such as tiredness， which is almost twice as frequent as in younger patients and which， together with comorbidity， makes clinical judgement very difficult and unreliable. Recently Jourdain et al. reported that in optimally treated CHF patients， a BNP-guided strategy reduced the risk of CHF-related death or hospital stay due to CHF. The result was mainly obtained through an increase in ACEI and beta-blocker doses. Despite similar baseline clinical characteristics， at the end of the first 3 months all types of drugs were changed more frequently and mean ACEI and beta-blocker dosages were significantly higher in the BNP group (P < 0.05)， whereas the mean furosemide dosage increase was similar in both groups. During the follow-up (median 15 months)， significantly fewer patients in the BNP group achieved the combined end point.
 
Another frequently discussed issue is tolerability in the elderly. Some studies as well as experience indicate that both ACE inhibitors and beta blockers are well tolerated by elderly patients. The MERIT-HF subgroup analysis demonstrated that metoprolol CR/XL was easily administered， safe and well tolerated in elderly patients with systolic heart failure. Likewise in SENIORS， nebivolol was shown to be well tolerated by the elderly.
 
Are they equally well tolerated by 65 and 85 year olds?
 
Probably not. Most studies of the so-called “elderly” usually comprise a population of around 65–75 years and the very elderly group (octogenarians)， i.e. > 80 years old， is rarely studied. Moreover， tolerability is one thing and efficacy is another. Due to the present lack of clinical data e.g. in ACEI and aldosteron receptor antagonist， we are trying to extrapolate the available evidence from younger patients to an elderly heart failure population. The question is whether this has been validated and how wrong can the interpretation be. Paradoxically， older patients seem to derive more benefit than younger ones， although this type of relationship may not be linear. This senior heart failure population is generally less s