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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Early invasive strategy in elderly patients with non-ST-elevation acute coronary syndromes

Francesco Liistro*, Kenneth Ducci, Giovanni Falsini and Leonardo Bolognese

Cardiovascular Department, San Donato Hospital, Arezzo, Italy

* Corresponding author. Tel: +39 575254070; fax: +39 575254073. E-mail address: francescoliistro{at}hotmail.com


   Abstract
Top
 Abstract
Introduction
 Conclusion
 References
 
The clinical impact of an early invasive strategy (EIS) on elderly patients with acute coronary syndromes (ACSs) has yet to be completely defined because of the poor enrolment of elderly patients in randomized trials in this setting. The reluctance to treat elderly ACS patients is mainly due to the higher risk profile of these patients when percutaneous or surgical revascularization is planned. However, recent clinical data from different centres strongly support the use of an EIS in the elderly, showing a significantly larger absolute reduction in 30-day major adverse clinical events in elderly patients than that in younger patients, and prompt the need for dedicated randomized trials.

Key Words: ACS • Early invasive strategy • Elderly


   Introduction
Top
 Abstract
 Introduction
Conclusion
 References
 
Elderly patients (aged ≥75) represent ~30% of the total population requiring medical care for acute coronary syndromes (ACSs). Several recent randomized trials have demonstrated the positive clinical impact of an early invasive strategy (EIS) (including the routine use of diagnostic catheterization and revascularization as indicated) when compared with that of a conservative approach in patients with non-ST-elevation (NSTE).1–3 The benefit of an EIS is particularly evident in patients with ST-changes and/or elevated levels of cardiac biomarkers. However, elderly patients were significantly under-represented in these trials, and a final decision concerning the best strategy to apply in this subset of patients has yet to be made, leaving physicians who deal with this problem on a daily basis with a degree of uncertainty. The under-usage of an EIS in the elderly compared with that in younger population4–6 is probably due to the higher rate of comorbid conditions and the greater extent of coronary artery disease in these patients, which carry a high procedural risk when percutaneous or surgical coronary revascularization is planned.4,7–10 In contrast, elderly patients with NSTE-ACS are more likely to present with elevated levels of cardiac biomarkers and ST-changes than younger patients, variables associated with a high rate of 30-day ischaemic complications, including myocardial infarction (MI) and death.4,8,11

In the early 1990s, the VANQWISH (Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital)12 and TIMI IIIB [Thrombolysis in Myocardial Ischemia (Phase III)]13 trials gave contradictory results on the effectiveness of an EIS in NSTE-ACS patients aged >65. Today, however, these results cannot be held valid, as the age threshold for those considered ‘elderly’ has since been extended by 10 to ≥75 years. Furthermore, among the elderly cohort, age itself represents a risk factor and clinical outcome should be reported separately in septuagenarians, octogenarians, and nonagenarians. The finding from a recent study by Halon et al.5 that an increase of 10 years in age was associated with a doubling in mortality among elderly patients with NSTE-ACS underlines this point.

The fast and continuous evolving of catheter-based coronary interventions, with the introduction of new coronary stent concepts and dedicated haemodynamic support systems, together with a growing pharmacological armamentarium aimed at reducing procedurally related ischaemic complications, have allowed the achievement of optimal angiographic and clinical results even in complex coronary patients, such as the elderly. Furthermore, the possibility of performing off-pump coronary surgery has enabled the treatment of patients considered unsuitable for catheter-based procedures, thus minimizing procedural risk in such friable patients. These advances in revascularization techniques may explain the improved clinical outcome in elderly patients with stable angina undergoing elective coronary angiography and revascularization when compared with those being treated medically, as observed in TIME (Trial of Invasive Versus Medical Therapy in Elderly Patients with Chronic Symptomatic Coronary-Artery Disease).14 These results have been confirmed in a larger retrospective study including 6181 patients aged >70, of whom >50% suffered from ACS.15 In this study, myocardial revascularization was associated with higher risk adjusted survival rates when compared with medical treatment [4-year adjusted survival percentage: 65% for medical treatment, 72% for percutaneous coronary intervention (PCI), and 77% for coronary artery bypass grafting (CABG); P<0.001], particularly in octogenarians who had a greater absolute risk reduction than in younger patients. In a recently published registry of 1581 consecutive patients with NSTE-ACS, a conservative strategy appeared to be an independent predictor [odds ratio (OR), 2.31; 95% CI, 1.20–4.48) of 30-day events among the elderly cohort (564 patients).4 It has to be underlined that in this study, an EIS was applied in a minority of patients (39%) who were at lower risk of acute events. The results might not therefore have been the same if an EIS had been systematically applied in the total elderly cohort, including those at higher risk.

The clinical benefit of an EIS in elderly patients with NSTE-ACS has also been reported in a recent post hoc analysis of the TACTICS TIMI 18 (Treat Angina with Aggrastat and Determine Cost of Therapy with Invasive or Conservative Strategy—Thrombolysis in Myocardial Infarction 18) trial, in which the 6-month rate of death or MI was 10.8% in elderly patients treated with an EIS and 21.6% in those treated conservatively (P=0.01), with the need to treat only nine patients invasively to prevent one death or non-fatal MI at 6 months.11 In contrast, this study also demonstrated that the invasive approach was associated with a slightly higher bleeding risk in the elderly, probably related to the use of glycoprotein IIb/IIIa antagonists. The limitations of these data include the exclusion of elderly patients with serious comorbid conditions (who are frequently observed in daily practise) and that the study was powered to detect the difference in endpoint occurrence in a wide population and not specifically in the elderly. However, similar findings have been previously reported8 in 159 consecutive elderly patients with NSTE-ACS treated with an EIS, with a myocardial revascularization rate of 85% (PCI 63%; CABG 22%) and a combined endpoint of death or non-fatal MI of 5.3% at 30 days and of 10.3% in the long-term. Interestingly, 30-day mortality was 1.9% in PCI-treated patients vs. 6.4% in those undergoing CABG and long-term cardiac mortality was 2.9 vs. 19.3%, respectively (P=0.005). This observation could be explained by the higher EuroSCORE16 of elderly patients undergoing cardiac surgery. Similar results for cardiac surgery in elderly patients with NSTE-ACS were reported by a single institution in a series of 601 octogenarians undergoing isolated CABG, with an overall in-hospital mortality of 9.1% (ranging from 6.7% in elective procedures to 21% in emergent procedures),17 and in a larger experience of 4743 octogenarians undergoing CABG in 22 different cardiac centres, with an in-hospital mortality of 8.1%.9 In both studies, emergent surgery, low left ventricular ejection fraction, renal and respiratory insufficiency, and carotid vascular disease were predictors of mortality. Although surgical revascularization may better guarantee the completeness of myocardial revascularization in elderly patients, PCI, albeit incomplete or deliberately targeted to treat only the culprit lesion, may be the best choice in patients at high surgical risk.


   Conclusion
Top
 Abstract
 Introduction
 Conclusion
References
 
In conclusion, the data from single centre experiences and from a retrospective analysis of a major randomized trial show that an EIS, although under-used in elderly NSTE-ACS patients, is feasible, leads to coronary revascularization in the majority of patients, and appears clinically more beneficial than a conservative approach. Only dedicated randomized trials will provide a more complete all-around vision of this emerging clinical issue.

Conflict of interest: none declared.


   References
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 Abstract
 Introduction
 Conclusion
 References
 

  1. Cannon CP, Weintraub WS, Demopoulos LA et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:1879–1887.[Abstract/Free Full Text]
  2. Fragmin and Fast Revascularisation during Instability in Coronary Artery Disease Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354:708–715.[CrossRef][ISI][Medline]
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  5. Halon DA, Adawi S, Dobrecky-Mery I et al. Importance of increasing age on the presentation and outcome of acute coronary syndromes in elderly patients. J Am Coll Cardiol 2004;43:346–352.[Abstract/Free Full Text]
  6. Giugliano RP, Camargo CA Jr, Lloyd-Jones DM et al. Elderly patients receive less aggressive medical and invasive management of unstable angina: potential impact of practice guidelines. Arch Intern Med 1998;158:1113–1120.[Abstract/Free Full Text]
  7. 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.[Abstract/Free Full Text]
  8. Liistro F, Angioli P, Falsini G et al. Early invasive strategy in elderly patients with non ST elevation acute coronary syndrome: comparison with younger patients on 30-day and long-term outcome. Heart. Published online ahead of print March 10, 2005.
  9. Alexander KP, Anstrom KJ, Muhlbaier LH et al. Outcomes of cardiac surgery in patients> or =80 years: results from the National Cardiovascular Network. J Am Coll Cardiol 2000;35:731–738.[Abstract/Free Full Text]
  10. Batchelor WB, Anstrom KJ, Muhlbaier LH et al. Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: results in 7472 octogenarians. National Cardiovascular Network Collaboration. J Am Coll Cardiol 2000;36:723–730.[Abstract/Free Full Text]
  11. Bach RG, Cannon CP, Weintraub WS et al. The effect of routine, early invasive management on outcome for elderly patients with non-ST-segment elevation acute coronary syndromes. Ann Intern Med 2004;141:186–195.[Abstract/Free Full Text]
  12. Boden WE, O'Rourke RA, Crawford MH et al. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. N Engl J Med 1998;338:1785–1792.[Abstract/Free Full Text]
  13. Stone PH, Thompson B, Anderson HV et al. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry. JAMA 1996;275:1104–1112.[Abstract]
  14. TIME Investigators. Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial. Lancet 2001;358:951–957.[CrossRef][ISI][Medline]
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