European Heart Journal Advance Access originally published online on February 14, 2006
European Heart Journal 2006 27(7):887-888; doi:10.1093/eurheartj/ehi784
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Beta-blockers and heart failure in older people
Centre for Education and
Research on Ageing (CERA)
University of Sydney
Concord Hospital
Sydney NSW 2139
Australia
Tel: +612 9767 7212
Fax: +612 9767 5419
E-mail address: dlecouteur{at}med.usyd.edu.au
Centre for Education and
Research on Ageing (CERA)
University of Sydney
Concord Hospital
Sydney NSW 2139
Australia
Centre for Education and
Research on Ageing (CERA)
University of Sydney
Concord Hospital
Sydney NSW 2139
Australia
The role of beta-blockers in older people (>75 years) with heart failure has been prospectively studied in the SENIORS study1 and retrospectively analysed from trials of metoprolol.2 In the recently published editorial accompanying the SENIORS study, it was concluded that it ‘is disappointing to see how infrequently elderly patients are prescribed these effective treatments’.3
As geriatricians, our concerns about the increased prevalence of adverse drug reactions in older people frequently impacts on our decision to prescribe medications.4 However, in the case of beta-blockers and heart failure, we also have concerns about the efficacy data.
The SENIORS study states1 ‘As age was a particular focus of the SENIORS trial, we also analysed patient cohorts between median age (75.2 years) and 85 years (n=459 for nebivolol and n=482 for placebo), where the HR for the primary endpoint was 0.91 (95% CI 0.74–1.13), and for patients >85 years (n=69 for nebivolol and n=54 for placebo), where the HR was 1.32 (95% CI 0.73–2.37). There was no difference between the groups for hospitalization for heart failure [placebo 144 (13.7%), nebivolol 145 (13.9%), HR=0.99 (95% CI 0.79–1.25, P=0.95)]’. Thus, the data show that in the older cohort (>75.2 years) of the SENIORS study, there was no statistically significant efficacy.
In an analysis of clinical trials of metoprolol by Deedwania et al.,2 the risks of the primary outcomes also were not significant over the age of 75 years. The authors state: ‘There were 490 patients >75 years of age in total [mean age 77 years (1.5); mean ejection fraction 0.27 (0.07)], of whom 247 were randomized to placebo and 243 to metoprolol CR/XL. Of these, 34 patients died in the placebo group and 24 in the metoprolol CR/XL group (relative risk 0.71, 95% CI 0.42–1.19); corresponding data for sudden death were 17 vs. 8 deaths (0.47, 0.20–1.10), for death from heart failure 12 vs. 9 deaths (0.75, 0.32–1.77), and for the combined endpoint of all-cause mortality or hospitalization for worsening heart failure 67 vs. 53 patients (0.79, 95% CI 0.55–1.14)’.
How do we evaluate these results and apply them to our patients over 75 years? As epidemiologists, we could state that there is no statistical interaction between age and outcomes over a range of age cohorts. However, as geriatricians, is it not appropriate to ask the single question ‘are these drugs effective over the age of 75 years?’ In this case, the data fail to reach statistical significance. Furthermore, the lack of statistical benefit seen in this older age group is biologically plausible given the effects of age on beta receptors and clinically plausible given the effects of age on pharmacokinetics, comorbidity, and disease mechanisms.4
Until clinical trial data show unequivocal improvement in outcomes with beta-blockers in typical older heart failure patients with their comorbidities and polypharmacy, we believe that risk-to-benefit analysis should be undertaken for each individual patient, rather than simply applying blanket guidelines and then reproaching under-prescribing.
References
- Flather M, Shibata M, Coats A, Van Veldhuisen D, Parkhomenko A, Borbola J, Cohen-Solal A, Dumistrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Bohm M, Anker S, Thompson S, Poole-Wilson P. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005;26:215–225.
[Abstract/Free Full Text] - Deedwania PC, Gottlieb S, Ghali JK, Waagstein F, Wikstrand JC. Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure. Eur Heart J 2004;25:1300–1309.
[Abstract/Free Full Text] - McMurray J. Making sense of SENIORS. Eur Heart J 2005;26:203–206.
[Free Full Text] - McLean AJ, Le Couteur DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev 2004;56:163–184.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||