The elderly and the very elderly are the most rapidly growing segment of the population in the Western world.1–3 The prevalence of coronary artery disease rises with age, and coronary revascularization is commonly performed in elderly patients for treatment of stable and unstable coronary artery disease.4 Previous studies have found similar or even enhanced benefit of efficient revascularization in the elderly compared to younger patients.5,6 Further, not only is revascularization in the elderly associated with reduction in morbidity and mortality, revascularized patients consistently demonstrate better quality of life.7
There, however, remains a paucity of data on guiding optimal revascularization in elderly patients. Elderly patients have been underrepresented in most contemporary interventional trials. It is in this context that the study by Sanfilippo et al in the current issue comparing the benefit of two drug-eluting stent (DES) types for elderly patients is a welcome addition.8 Briefly, among a cohort of 207 patients over 75 years, those treated with a sirolimus-eluting stent (SES, n =116) were prospectively compared with those treated with paclitaxel-eluting stent (PES, n = 91). In a primary analysis, patients with SES had a higher incidence of major adverse cardiac events (MACE) (22.4% versus 10.0%; p = 0.04) during a mean follow-up duration of 23 months, while in a subsequent multivariate analysis, adjusting for clinical covariables, this difference was no longer significant. The study is small and underpowered to define optimal stent choice for this important population, and the results of this study need to be evaluated in the context of limited prior data.
Is there a biological reason to expect these stents to behave differently in the elderly? The proportion of women is likely to be higher in an older population, these patients have more comorbidities, lower left ventricular function and more complex lesions.9 The elderly are more likely to have worse renal function and diminished endothelial progenitor cells and potentially different neointimal healing. For bare-metal stents, some studies have suggested higher rates of restenosis in the elderly, while studies for DES (including SES and PES) did not confirm such a difference.10,11 Indeed, the safety and efficacy of DES have been well established in this population,12 although the exact choice of DES remains to be established. In a recent study evaluating PES, there was no difference in the relative benefit of PES (compared with DES) in the elderly compared to the young.13 Similarly, a large observational study from Germany has demonstrated relatively good outcomes in the elderly with SES.14 While randomized, controlled trials and meta-analyses have found SES to be marginally superior to PES,15 the elderly were underrepresented in these studies, and the decision to use a specific DES must be made based on data extrapolated from younger patients.
With this background, the findings of Sanfilippo et al of better outcomes with PES appear somewhat confusing. This was more likely driven by dissimilarity in patient characteristics, since after multivariate adjustment, this difference was no longer present.
Commendably, the study of Sanfilippo et al followed the patients very carefully, with no patients lost to follow up. Moreover, they have circumspectly adjusted for potential confounding variables in a multivariate analysis attempting to overcome the natural limitations of an observational study. However, such adjustments mainly depend on three crucial factors: first, relevant confounding variables have to be observable; secondly, they have to be effectively measured; and finally, they have to be included in the multivariate analysis model. Importantly, vessel diameter has not been considered in the present study; an imbalance in other unobserved variables is certainly possible as well. It has been illustrated that such adjustments, even when performed carefully, are often insufficient to exclude any residual confounding variables.16
Due to limitations inherited with observational studies, the presented data are quite insufficient to reach a conclusion on superiority or equivalence of SES or PES in elderly patients.
Furthermore, there are currently four commercially available DES in the U.S. and the question of which is the optimal stent must be extended beyond SES and PES to include zotarolimus-eluting and everolimus-eluting stents as well. One of the most important contributions of this study is to direct attention to this growing patient segment whose importance has probably been underestimated hitherto. Their importance will continue to increase in the coming years due to a skewed age pyramid and to efficient prevention of cardiovascular events based on continuously improving medical treatment. We hope that this study will encourage larger, better-designed trials focused on defining the best strategies for treating elderly patients with coronary artery disease!
From the University of Michigan School of Medicine, Ann Arbor, Michigan and VA Ann Arbor Healthcare System, Ann Arbor, Michigan.
The author reports no conflicts of interest regarding the content herein.
Address for correspondence: Hitinder S. Gurm, MD, University of Michigan Cardiovascular Center, Floor 2A 394, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5853. E-mail: hgurm@med.umich.edu
1. Population Profile of the United States, U.S. Census Bureau, 2008. http://www.census.gov/population/www/pop-profile/elderpop.html.
2. Manton KG, Lowrimore GR, Ullian AD, et al. Labor force participation and human capital increases in an aging population and implications for U.S. research investment. Proc Natl Acad Sci USA 2007;104:10802–10807.
3. Manton KG, Gu X, Lamb VL. Change in chronic disability from 1982 to 2004/2005 as measured by long-term changes in function and health in the U.S. elderly population. Proc Natl Acad Sci USA 2006;103:18374–18379.
4. McKellar SH, Brown ML, Frye RL, et al. Comparison of coronary revascularization procedures in octogenarians: A systematic review and meta-analysis. Nat Clin Pract Cardiovasc Med 2008;5:738–746.
5. Graham MM, Ghali WA, Faris PD, et al. Survival after coronary revascularization in the elderly. Circulation 2002;105:2378–2384.
6. Pfisterer M, Buser P, Osswald S, et al. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive vs. optimized medical treatment strategy: One-year results of the randomized TIME trial. JAMA 2003;289:1117–1123.
7. Graham MM, Norris CM, Galbraith PD, et al. Quality of life after coronary revascularization in the elderly. Eur Heart J 2006;27:1690–1698.
8. Sanfilippo A, Cumbo M, Caggegi A, et al. Long-term outcomes comparison of different types of DES in elderly patients from a real world experience. J Invasive Cardiol 2009;21:330–333.
9. Matetzky S, Sharir T, Noc M, et al. Primary angioplasty for acute myocardial infarction in octogenarians. Am J Cardiol 2001;88:680–683.
10. De Gregorio J, Kobayashi Y, Albiero R, et al. Coronary artery stenting in the elderly: Short-term outcome and long-term angiographic and clinical follow-up. J Am Coll Cardiol 1998;32:577–583.
11. Vlaar PJ, Lennon RJ, Rihal CS, et al. Drug-eluting stents in octogenarians: Early and intermediate outcome. Am Heart J 2008;155:680–686.
12. Douglas PS, Brennan JM, Anstrom KJ, et al. Clinical effectiveness of coronary stents in elderly persons: Results from 262,700 Medicare patients in the American College of Cardiology-National Cardiovascular Data Registry. J Am Coll Cardiol 2009;53:1629–1641.
13. Forman DE, Cox DA, Ellis SG, et al. Long-term paclitaxel-eluting stent outcomes in elderly patients. Circ Cardiovasc Intervent 2009; published online ahead of print (DOI 10.1161/CIRCINTERVENTIONS.109.855221).
14. Wiemer M, Langer C, Kottmann T, et al. Outcome in the elderly undergoing percutaneous coronary intervention with sirolimus-eluting stents: Results from the prospective multicenter German Cypher Stent Registry. Am Heart J 2007;154:682–687.
15. Gurm HS, Boyden T, Welch KB. Comparative safety and efficacy of a sirolimus-eluting versus paclitaxel-eluting stent: A meta-analysis. Am Heart J 2008;155:630–639.
16. Stukel TA, Fisher ES, Wennberg DE, et al. Analysis of observational studies in the presence of treatment selection bias: Effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods. JAMA 2007;297:278–285.
