Percutaneous Coronary Intervention in the Elderly Patient (Part II of II)

Continued (Part II of II) Cardiogenic Shock Although several registries suggest that elderly patients who present with cardiogenic shock have a significant improvement in survival with PCI, neither the SHOCK trial nor the Northern New England Shock Study showed much benefit, and may have shown worse outcomes. These studies demonstrated 34% and 12% absolute differences, respectively in early mortality between elderly patients and younger patients with shock treated with PCI. Elderly patients with cardiogenic shock was one subject of the very complex SHOCK trial65 and registry.⁶⁶ The SHOCK trial⁶⁵ randomized 302 patients in cardiogenic shock to early revascularization therapy or to initial medical stabilization. There was significantly lower 6-month mortality in patients randomized to revascularization (PCI or surgical) than those treated medically, but this benefit was observed only in patients 75 years did not appear to benefit from a routine strategy of early revascularization. The 30-day survival of patients greater than or equal to 75 years was worse (20.8% vs. 34.4%) in those treated with emergency revascularization. Hochman⁶⁷ did not believe these data were definitive, and suggested that baseline differences could have been the determining factor. The principal investigator of SHOCK identified the fact that there were only 56 patients 75 years of age or older enrolled in the SHOCK trial, and hence, a definitive conclusion in this subgroup was not possible. Additionally, the mortality rate for patients > 75 years of age who received initial medical stabilization was similar to younger patients, and was therefore unexpectedly low (53.1%), further qualifying the conclusion. Inequalities in baseline characteristics of the 56 elderly patients assigned to the emergency revascularization group compared to the medical therapy group may also have contributed to an apparent lack of treatment effect.⁶⁷ Conversely, the SHOCK Registry, based on 277 elderly shock patients, did show a marked survival benefit favoring PCI in the elderly.⁶⁶ Elderly patients clinically selected for emergency revascularization demonstrated improved survival when treated with emergent PCI. Interestingly, the mean age of randomized patients was lower than registry patients (65.8 vs. 68.5 years; p 67–69 In these registries, between 16% and 33% of elderly patients with shock were selected for emergency PCI. The Northern New England Cardiovascular Registry⁶⁸ evaluated the results in cardiogenic shock patients over a 10-year experience in their prospective registry in Northern New England. The clinical characteristics and in hospital mortality for elderly patients > 75 years of age were compared to those 70 In patients without shock, the adjusted relative risk for long-term mortality was 4.4 in older versus younger patients (p p = 0.051). This finding suggests that certain elderly shock patients are highly salvageable. Among the elderly cardiogenic shock patients, estimated 1-year and 5-year survival rates were 38% and 24%.⁶⁸ In an observational study of 61 patients greater than or equal to 75 years (mean age 79.5 ± 3 years) treated with primary PCI for AMI with cardiogenic shock, 56% of patients survived to hospital discharge, and the 30-day mortality was 47%. Of the survivors, 75% were alive at 1 year.⁶⁹ In 55 octogenarians (mean age 84 ± 3 years) undergoing primary PCI for AMI, 30-day mortality was 4% in patients without cardiogenic shock and 70% in those with shock. The overall 1-year survival rate was 77%. Prasad⁷¹ prospectively evaluated whether physician judgment could be used to determine accurately which elderly shock patients would benefit from emergency PCI. These Mayo Clinic data confirmed that elderly patients selected by their physicians for PCI had better survival than those treated conservatively. Non-STEMI and Unstable Angina The optimal management of elderly patients with acute coronary syndrome has not been the subject of a dedicated clinical trial. Thus, the proper role of PCI can only be surmised from small series and subgroup analyses of larger studies. Ferguson⁷² published an experience of 88 consecutive patients over the age of eighty who had percutaneous coronary intervention for refractory angina. Procedural success was achieved in 86% with an in-hospital MACE rate of 7% (6/88). However, there were 3 in-hospital deaths in this group. The 30-day and 1-year MACE rates were 10% and 20%, respectively. During follow up, 59% remained free of angina, and only 6% required readmission for chest pain. In TIMI-3,⁷³ advanced age was a stronger predictor of 6-month mortality than other clinical variables, including cardiac serum markers. Bach and colleagues⁷⁴ retrospectively analyzed patients over the age of 75 enrolled in the TACTICS-TIMI 18 trial. The authors found that despite an increased risk of major bleeding, a routine early invasive strategy significantly improved the 30-day and 6-month outcomes, including death, nonfatal MI, rehospitalization, stroke and hemorrhage. The authors demonstrated that the early invasive strategy was associated with an absolute risk reduction of 4.8% compared with the conservative strategy (8.8% versus 13.6%; p = 0.018), and a relative reduction of 39% in death or MI at 6 months. Interestingly, the outcomes of the two strategies were similar among patients younger than 65 years of age. The positive findings of the TACTICS-TIMI 18 trial⁷⁵ that are so widely publicized were primarily due to the elderly subgroup, a fact that is underappreciated. Age alone was not a determinant of outcome after PCI for acute coronary syndromes, but the combination of age with other comorbidities was a very powerful and dramatic predictor. Nevertheless, the critical message is that PCI can provide significant symptomatic relief in many elderly patients. Elective PCI Elective PCI in the elderly is the single clinical situation that has been tested in a dedicated, randomized clinical trial. This study is the TIME trial, which examined invasive versus medical therapy in elderly patients with chronic, symptomatic CAD.⁷⁶ This is a randomized study of patients aged 75 years and older comparing an invasive strategy versus optimal medical therapy in patients with Canadian Classification Class II or higher (mean 3.2) who were on at least two anti-anginal medications. The mean age of patients in this study was 80 ± 4 years; 23% were diabetic and 44% were women. Endpoints included quality of life measures as well as MACE (death, nonfatal MI, recurrent ischemic events and acute coronary syndromes) at six months. In the initial publication, it was clear that there was significant crossover between those assigned to optimal medical therapy and those assigned to invasive therapy. Of the 150 patients randomized to optimal medical therapy, 37% ultimately underwent a coronary intervention on subsequent hospital admissions. Further, about 30% of those assigned to the invasive arm were actually treated medically. The primary endpoint of any MACE was substantially improved by undergoing invasive therapy and intervention anytime within the first year. This finding was present regardless of whether the initial management was invasive or medical. The benefit was primarily due to a decreased incidence of recurrent acute coronary syndromes. Death and nonfatal MI as a combined endpoint were no different, and, in fact, there was a trend toward an increased incidence of death in the invasive group. However, half of the deaths in the invasive group were in patients who were unwilling to undergo or deemed by the physicians to be unsuitable for coronary intervention or bypass surgery. In TIME, quality of life was evaluated using multiple scores and indices. There were no differences in the quality of life at baseline between those randomized to the invasive strategy versus those randomized to optimal medical therapy. At 6 months, all groups had an improved quality of life, but the invasive group enjoyed the largest increment in well-being. Hence, a strategy of early angiography and revascularization resulted in decreased MACE and improved quality of life compared to a conservative strategy of optimization of medical therapy in elderly patients with stable angina. However, the invasive strategy was associated with a trend toward increased mortality. Pfisterer⁷⁷ expanded these results to one-year follow up. Improvements in angina and quality of life persisted in both therapies compared to baseline, but the early difference favoring invasive therapy disappeared. However, late hospitalization remained less frequent in the invasive group (10% versus 46%; p p 78 At this follow-up point, it is clear that MACE, especially nonfatal MI, were more frequent in the medically-treated group. Anginal relief and quality-of-life improvements were maintained in both groups equally. Revascularization within the first year improved survival in both invasive- and medically-assigned patients to a similar degree. TIME is highly commendable as a dedicated clinical trial interrogation, and adequately tested various strategies in elderly patients with CAD. The major problems with TIME are its relatively small size, compounded by the high cross-over rate. Consequently, there is inadequate power to determine the relative risk of cardiac mortality on the basis of initial strategy. Nevertheless, this excellent study is as convincing as any which will be performed in this subgroup of patients. Its conclusion is that a strategy of medical stabilization prior to revascularization for Classes III or IV angina is reasonable as long as the delay to revascularization is less than one year. Summary The elderly population is a rapidly growing segment of patients with coronary disease, and they present unique physiologic and anatomic problems. These patients are poorly represented in randomized clinical trials, hence management guidelines based on strong evidence are lacking. Elderly cardiac patients are treated less aggressively than younger patients in part because of the concern over an increased incidence of adverse events and complications. However, the lack of hard data on the relative therapeutic benefits of PCI compared to medical therapy renders it impossible to be certain what strategy is optimal in most clinical scenarios. The decision to perform PCI should not be based on chronologic age alone. Physiologic age and emotional health are extremely important considerations. The appropriate decision considers the significance of noncardiac comorbidities, the ability of the patient to purchase and tolerate drugs, the patient’s and family’s expectations of the outcome, and the technical feasibility of performing PCI. Enhancing personal independence and quality of life may be important goals of therapy, not just survival. PCI in the elderly carries a higher risk of acute coronary and other vascular complications. Age is clearly an independent risk factor for more complications and periprocedural mortality. However, the magnitude of risk depends strongly on the presence and severity of associated angiographic and clinical factors associated with increased risk in every patient undergoing PCI, especially comorbidities. Characterization as “elderly” using whatever age cutoff is appropriate does constitute a high-risk variable. PCI in the elderly improves quality of life, but there may be an early cost in morbidity to achieve this outcome. Therefore a critical and conservative assessment of strategy and risk assessment is appropriate. Careful case selection using sound clinical judgment based on the patient’s pre-illness mental status, physical condition, and quality of life is of paramount importance. Additionally, to further improve outcomes of PCI, interventionists should be mindful of the most likely complications and perform these procedures with attention to detail. The management of these patients would be improved with more studies in specific circumstances. These would ideally include studies dedicated to determining: (1) the outcomes in different age groups within the elderly population; (2) how to better select cases based on mental status and activity level; and (3) which comorbid conditions and clinical factors predict high risk, and conversely, those patients most likely to benefit from PCI. Most critical is the need for specifically designed trials (and not merely post hoc subgroup analyses of PCI outcomes) in patients with particular clinical presentations of ischemic heart disease.

1. Lee PY, Alexander KP, Hammill BG, et al. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA 2001;286:708–713. 2. Gregoratos G. Clinical manifestations of acute myocardial infarction in older patients. Am J Geriatr Cardiol 2001;10:345–347. 3. Rathore SS, Mehta RH, Wang Y, et al. Effects of age on the quality of care provided to older patients with acute myocardial infarction. Am J Med 2003;114:307–315. 4. Sheifer S, Rathore S, Gersh B, et al. Time to presentation with acute myocardial infarction in the elderly: Associations with race, sex, and socioeconomic characteristics. Circulation 2000;102:1651–1656. 5. Wennberg DE, Makenka DJ, Sengupta A, et al. Percutaneous transluminal coronary angiography in the elderly: Epidemiology, clinical risk factors and in-hospital outcomes. The Northern New England Cardiovascular Disease Study Group. Am Heart J 1999;137:639–645. 6. Shaw R, Anderson H, Brindis R, et al. Development of a risk adjustment mortality model using the American College of Cardiology- National Cardiovascular Data Registry (ACC-NCDR) experience: 1998–2000. J Am Coll Cardiol 2002;39:1104–1112. 7. Hirshfield JW, Schwartz RS, Jugo R, et al. for the M-Heart Investigators. A multivariate statistical model to relate lesion and procedure variables to restenosis. J Am Coll Cardiol 1991;18:647–656. 8. Batchelor WB, Anstrom KJ, Muhlbaier LH, et al. for the NCN. Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: Results in 7,472 octogenarian. J Am Coll Cardiol 2000;36:723–730. 9. Vijaykumar M, Lemos PA, Haze A, et al. Effectiveness of sirolimus-eluting stent implantation for the treatment of coronary artery disease in octogenarian. Am J Cardiol 2004;94:909–913. 10. Taddei CF, Weintraub WS, Douglas JS, et al. Influence of age on outcome after percutaneous transluminal coronary angioplasty. Am J Cardiol 1999;84:245–251. 11. Peterson ED, Jullis JG, Bebchuk JD, et al. Changes in mortality after myocardial revascularization in the elderly. The National Medicare experience. Ann Intern Med 1994;121:919–927. 12. Hannan EL, Arani DT, Johnson LW, et al. Percutaneous transluminal coronary angioplasty in New York State. Risk factors and outcomes. JAMA 1992;268:3092–3097. 13. Laskey WK, Kimmel S, Krone RJ. Contemporary trends in coronary intervention: A report from the Registry of the Society for Cardiac Angiography and Interventions. Catheter Cardiovasc Interv 2000;49:19–22. 14. Thompson RC, Holmes DR, Grill DE. Changing outcome of angioplasty in the elderly. J Am Coll Cardiol 1996;27:8–24. 15. Rich JJ, Crispino CM, Saporito JJ, et al. Percutaneous transluminal coronary angioplasty in patients 80 years of age and older. Am J Cardiol 1990;65:675–676. 16. Kelsey SF, Miller DP, Holubkov R, et al. Results of percutaneous transluminal coronary angioplasty in patients ? 65 years of age (from the 1985 to 1986 National Heart, Lung and Blood Institute’s coronary angioplasty registry). Am J Cardiol 1990;66:1033–1038. 17. MacDonald P, Johnstone D, Rockwood K. Coronary artery bypass surgery for elderly patients: Is our practice based on evidence or faith? Can Med Assoc J 2000;162:1005–1006. 18. Mehta RH, Rathore SS, Radford MJ, et al. Acute myocardial infarction in the elderly: Differences by age. J Am Coll Cardiol 2001;38:736–741. 19. Guyon P, Urban P, Lotanr C, et al. The impact of sirolimus-eluting stent implantation in the elderly: A report from the e-Cypher Registry (Abstr). Circulation 2004;110:II–3009. 20. Tu JU, Pashos CL, Naylor CD, et al. Use of cardiac procedures and outcomes in elderly patients with myocardial infarction in the United States and Canada. N Engl J Med 1997;336:1500–1505. 21. Graham MM, Ghali WA, Faris PO, et al. Survival after coronary revascularization in the elderly. Circulation 2002;105:2378–2383. 22. Seto TB, Taira DA, Berezin R, et al. Percutaneous coronary revascularization in elderly patients: Impact on functional status and quality of life. Ann Intern Med 2000;132:955–958. 23. The BARI Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. N Engl J Med 1996;335:217–225. 24. Windecker S, Remondino A, Eberli FR, et al. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization. N Engl J Med 2005;353:653–662. 25. Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein blockade during percutaneous coronary intervention. JAMA 2003;289:853–863. 26. The ESPRIT Investigators. The ESPRIT Study: A randomized, placebo-controlled trial of a novel dosing regimen of eptifibatide in planned coronary stent implantation. Lancet 2000;356:2037–2044. 27. Ferrari AU, Radaelli A, Centala M. Aging and the cardiovascular system. J Appl Physiol 2003;95:2591–2597. 28. Lansky AJ, Hochman JS, Ward PA, et al. Percutaneous coronary intervention and adjunctive pharmacotherapy in women: A statement for healthcare professionals from the American Heart Association. Circulation 2005;111:940–953. 29. Williams MA, Fleg JL, Ades PA, et al. Secondary prevention of heart disease in the elderly (with emphasis on patients > 75 years of age). Circulation 2002;105:1735–1743. 30. Halon DA, Adawi S, Dobrecky-Mery I, Lewis BS. Importance of increasing age on the presentation and outcome of acute coronary syndromes in elderly patients. J Am Coll Cardiol 2004;43:346–352. 31. Mehta RH, Sadiq I, Goldberg RJ, et al. Effectiveness of primary percutaneous coronary intervention compared with that of thrombolytic therapy in elderly patients with acute myocardial infarction. Am Heart J 2004;147:253–259. 32. Klein LW, Block P, Brindis R, et al. Percutaneous coronary interventions in octogenarian in the American College of Cardiology - National Cardiovascular Data Registry: Development of a nomogram predictive of in-hospital mortality. J Am Coll Cardiol 2002;40:349–402. 33. 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. 34. De Geare V, Stone G, Grines L, et al. Angiographic and clinical characteristics associated with increased in-hospital mortality in elderly patients with acute myocardial infarction undergoing percutaneous intervention (A pooled analysis of the primary angioplasty in myocardial infarction trials). Am J Cardiol 2000;86:30–34. 35. Alexander K, Anstrom K, Muhlbaier L, et al. Outcomes of cardiac surgery in patients greater than or equal to 80 years old: Results from National Cardiovascular Network. J Am Coll Cardiol 2000;35:731–738. 36. Eckart RE, Shry EA, Simpson DF, Stajduhar KC. Percutaneous coronary intervention in the elderly: Procedural success and one year outcome. Am J Geriatr Cardiol 2003;12:366–368. 37. Voudris VA, Skoulargis JJ, Malakos JS, et al. Long-term clinical outcome of coronary artery stenting in elderly patients. Cor Artery Dis 2002;13:323–329. 38. Dynina O, Vakile BA, Slater JN, et al. In hospital outcomes of contemporary percutaneous coronary interventions in the very elderly. Catheter Cardiovasc Interv 2003;58:352–357. 39. Clark MA, Bakhai A, Lacey MT, et al. Clinical and economic outcomes of percutaneous coronary intervention in the elderly. Circulation 2004;110:259–264. 40. Aronow WS. Select MI. Prevalence and prognosis in older patients diagnosed by routine electrocardiograms. Geriatrics 2003;58:24–26, 36–40. 41. Rich MW. Treatment of myocardial infarction. Ger Cardiol 2001;10:328–336. 42. Gurwitz JH, Col WF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA 1992;268:1617–1422. 43. Lee KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Circulation 1995;91:1659–1668. 44. Van de Werf F, Topol EJ, Lee KL, et al for the GUSTO Investigators. Variations in patient management and outcomes for acute myocardial infarction in the United States and other countries. Results from the GUSTO trial. JAMA 1995;273:1586–1591. 45. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: Collaborative overview of mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet 1994;343:311–322. 46. Thiemann DR. Primary angioplasty for elderly patients with myocardial infarction: Theory, practice and possibilities. J Am Coll Cardiol 2002;39:1729–1732. 47. Thiemann DR, Coresh J, Schulman SP, et al. Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years. Circulation 2002;101:2239–2246. 48. Silber S, Albertsson P, Aviles FF, et al. Guidelines for percutaneous coronary interventions: The task force for percutaneous coronary interventions of the European society of cardiology. Eur Heart J 2005;26:804–847. 49. Mehta RH, Granger CB, Alexander KP, et al. Reperfusion strategies for acute myocardial infarction in the elderly: Benefits and risks. J Am Coll Cardiol 2005;45:471–478. 50. The GUSTO V Investigation. Reperfusion therapy for acute myocardial information with fibrinolytic toe therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition. Lancet 2001;357:1905–1914. 51. Gersh BJ, Stone GW, White HD, Holmes DR Jr. Pharmacological facilitation of primary percutaneous intervention for acute myocardial infarction. JAMA 2005;293:979–986. 52. Ellis SG, Armstrong B, Betrim A, et al. Facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention: Design and rationale of the FINESSE trial. Am Heart J 2004;147:E162. 53. Zahn R, Schiele R, Schneider S, et al. Primary angioplasty verses intravenous thrombolysis in acute myocardial infarction: Can we define subgroups of patients benefiting most from primary angioplasty? Results from the pooled data of the Maximal Infarction Registry. J Am Coll Cardiol 2001;37:1827–1835. 54. Berger AK, Radford MJ, Wang Y, Krumholz HM. Thrombolytic therapy in older patients. J Am Coll Cardiol 2000;36:366–374. 55. Berger AK, Radford MJ, Krumholz HM. Factors associated with delay in reperfusion therapy in elderly patients with acute myocardial infarction: Analysis of the cooperative cardiovascular project. Am Heart J 2000;139:985–992. 56. Soumerai SB, McLaughlin TJ, Ross-Degnan D, et al. Effectiveness of thrombolytic therapy for acute myocardial infarction in the elderly: Cause for concern in the old-old. Arch Intern Med 2002;162:561–568. 57. GUSTO IIb Angioplasty Substudy Investigations. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activation for acute myocardial infarction. N Engl J Med 1997;336:1621–1628. 58. Klein LW, Anderson HV, Brindis R, et al. on behalf of the ACC-NCDR. Predictors of outcome of primary PCI in ST segment elevation myocardial infarction in 6521 consecutive cases during 2001: A report from the American College of Cardiology-National Cardiovascular Data Registry. Circulation 2002;106:II-363. 59. Guagliumi G, Stone GW, Cox DA, et al. Outcome in elderly patients undergoing primary coronary intervention for acute myocardial infarction: Results from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Circulation 2004;110:1598–1604. 60. Halkin A, Stone GW, Grines CG, et al. Outcomes of patients consented but not randomized in a trial of primary percutaneous coronary intervention in acute myocardial infarction (the CADILLAC Registry). Am J Cardiol 2005;96:1649–1652. 61. Montalescot G, Barragan P, Wittenberg D, et al. for the Admiral Investigation. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001;34:1895–1903. 62. Antoniucci D, Rodriguez A, Hempel A, et al. A randomized trial comparing primary infarct artery stenting with or without abciximab in acute myocardial infarction. J Am Coll Cardiol 2003;42:1879–1885. 63. Abbas AE, Brodie B, Dixon S, et al. Incidence and prognostic impact of gastrointestinal bleeding after percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2005;96:173–176. 64. Moriel M, Behar S, Tzivoni D, et al. Management and outcomes of elderly women and men with acute coronary syndromes in 2000 and 2002. Ann Int Med 2005;165:1521–1526. 65. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock? N Engl J Med 1999;341:625–634. 66. Dzavik V, Sleeper LA, Picard MH, et al. Outcomes of patients aged ? 75 years in the SHould we emergently revascularize Occluded coronary arteries in Cardiogenic shocK (SHOCK) Trial: Do elderly patients with acute myocardial infarction complicated by cardiogenic shock respond differently to emergent revascularization? Am Heart J 2005;149:1128–1134. 67. Dauerman HL, Goldberg RJ, Malinski M, et al. Outcomes and early revascularization for patients greater than or equal to 65 years of age with cardiogenic shock. Am J Cardiol 2001;87:844–848. 68. Dauerman HL, Ryan TJ Jr, Piper WD, et al. Outcomes of percutaneous coronary intervention among elderly patients in cardiogenic shock: A multicenter, decade-long experience. J Invasive Cardiol 2003;15:380–384. 69. Berger AK, Radford MJ, Krumholz HM. Cardiogenic shock complicating acute myocardial infarction in elderly patients: Does admission to a tertiary center improve survival? Am Heart J 2002;143:768–776. 70. Antoniucci D, Valenti R, Santoro GM, et al. Systematic primary angioplasty in octogenarian and older patients. Am Heart J 1999;138(4 Pt 1):670–674. 71. Prasad A, Lennon RJ, Rihal CS, et al. Outcomes of elderly patients with cardiogenic shock treated with early percutaneous revascularization. Am Heart J 2004;147:1066–1070. 72. Ferguson JD, Orr WP, McKenna CJ, et al. Percutaneous coronary intervention in octogenarian with refractory angina. Heart 2002;88:85–86. 73. 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. 74. 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. 75. Cannon CP, Weintraub, WS, Demopoulos LA, et al. for the TACTICS — Thrombolysis in Myocardial Infarction 18 Investigators. 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. 76. The TIME Investigators. Trial of invasive medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): A randomized trial. Lancet 2001;358:951–957. 77. Pfisterer M, Buser P, Osswald S, et al. for the TIME Investigators. Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive vs. optimal medical treatment strategy. One of results of the randomized TIME Trial. JAMA 2003;289:1117–1123. 78. Pfisterer M, for the TIME Investigators. Long-term care in elderly patients with clinical angina managed therapy by optimal medical therapy. Circulation 2004;110:1213–1218.