Skip to main content
SpringerLink
Log in

Pharmacological Treatment of Elderly Patients with Acute Coronary Syndromes without Persistent ST Segment Elevation

  • Therapy in Practice
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Evidence-based management of acute coronary syndromes (ACS) without persistent ST segment elevation involves a rational, stepwise approach to the selection of therapies with potential benefit for elderly patients. Specifically, in elderly patients with ACS without persistent ST segment elevation, therapy should be administered based on the likelihood of unstable angina or non-ST elevation myocardial infarction being present and the risks and benefits of each individual therapy. All elderly patients with suspected ACS should receive anti-ischaemic therapy consisting of β-blockers and nitrates, and antiplatelet therapy with aspirin unless clear contraindications exist. For patients with a moderate likelihood of ACS being present, defined as prior coronary disease or recurrent pain despite the use of anti-ischaemic therapies, unfractionated heparin or enoxaparin should be added to aspirin for more intense anticoagulation. In patients with high-risk clinical features, defined as ischaemic electrocardiographic changes and positive cardiac markers such as troponins, therapy with clopidogrel or glycoprotein IIb/IIIa inhibitors should be considered in addition to aspirin and heparin. Furthermore, high-risk patients should be managed with an early invasive strategy that includes prompt cardiac catheterisation within 24 to 48 hours and appropriate use of revascularisation as determined by the findings of the catheterisation. An evidence-based approach to the treatment of elderly patients with ACS without persistent ST segment elevation will help to improve the use of beneficial therapies and interventions that are recommended by current practice guidelines.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Table II
Fig. 2

Similar content being viewed by others

References

  1. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 1997; 349(9064): 1498–504

    Article  PubMed  CAS  Google Scholar 

  2. 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(6): 708–13

    Article  PubMed  CAS  Google Scholar 

  3. Boersma E, Pieper KS, Steyerberg EW, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation: results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation 2000; 101(22): 2557–67

    Article  PubMed  CAS  Google Scholar 

  4. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2000; 36(3): 970–1062

    Article  PubMed  CAS  Google Scholar 

  5. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined: a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000; 36(3): 959–69

    Article  PubMed  CAS  Google Scholar 

  6. Krumholz HM, Radford MJ, Wang Y, et al. National use and effectiveness of beta-blockers for the treatment of elderly patients after acute myocardial infarction: National Cooperative Cardiovascular Project. JAMA 1998; 280(7): 623–9

    Article  PubMed  CAS  Google Scholar 

  7. Krumholz HM, Philbin Jr DM, Wang Y, et al. Trends in the quality of care for Medicare beneficiaries admitted to the hospital with unstable angina. J Am Coll Cardiol 1998; 31(5): 957–63

    Article  PubMed  CAS  Google Scholar 

  8. Simpson Jr RJ, Weiser RR, Naylor S, et al. Improving care for unstable angina patients in a multiple hospital project sponsored by a federally designated quality improvement organization. Am J Cardiol 1997; 80(8B): 80H–4H

    PubMed  Google Scholar 

  9. Chen J, Radford MJ, Wang Y, et al. Do “America’s Best Hospitals” perform better for acute myocardial infarction? N Engl J Med 1999; 340(4): 286–92

    Article  PubMed  CAS  Google Scholar 

  10. Hasdai D, Berger PB, Bell MR, et al. The changing face of coronary interventional practice: the Mayo Clinic experience. Arch Intern Med 1997; 157(6): 677–82

    Article  PubMed  CAS  Google Scholar 

  11. Reynen K, Bachmann K. Coronary arteriography in elderly patients: risk, therapeutic consequences and long-term follow-up. Coron Artery Dis 1997; 8(10): 657–66

    Article  PubMed  CAS  Google Scholar 

  12. GUSTO III Investigators. A comparison of reteplase with alteplase for acute myocardial infarction: the global use of strategies to open occluded coronary arteries. N Engl J Med 1997; 337(16): 1118–23

    Article  Google Scholar 

  13. Flaherty JT. Nitrate tolerance: a review of the evidence. Drugs 1989; 37(4): 523–50

    Article  PubMed  CAS  Google Scholar 

  14. Cahalan MK, Hashimoto Y, Aizawa K, et al. Elderly, conscious patients have an accentuated hypotensive response to nitroglycerin. Anesthesiology 1992; 77(4): 646–55

    Article  PubMed  CAS  Google Scholar 

  15. Yusuf S, Collins R, MacMahon S, et al. Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials. Lancet 1988; 1(8594): 1088–92

    Article  PubMed  CAS  Google Scholar 

  16. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995; 345(8951): 669–85

    Article  Google Scholar 

  17. GISSI-3 Investigators. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravivenza nell’ infarto Miocardico. Lancet 1994; 343(8906): 1115–22

    Google Scholar 

  18. Gibbons RJ, Chatterjee K, Daley J, et al. ACC/AHA/ACPASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina). J Am Coll Cardiol 1999; 33(7): 2092–197

    Article  PubMed  CAS  Google Scholar 

  19. Anonymous. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 1981; 304(14): 801–7

    Google Scholar 

  20. The MIAMI Trial Research Group. Metoprolol in acute myocardial infarction (MIAMI): a randomised placebo-controlled international trial. Eur Heart J 1985; 6(3): 199–226

    Google Scholar 

  21. First International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction: ISIS-1. Lancet 1986; II(8498): 57–66

    Google Scholar 

  22. Roberts R, Rogers WJ, Mueller HS, et al. Immediate vs deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction: results of the thrombolysis in myocardial infarction (TIMI) II-B Study. Circulation 1991; 83(2): 422–37

    Article  PubMed  CAS  Google Scholar 

  23. Olsson G, Wikstrand J, Warnold I, et al. Metoprolol-induced reduction in postinfarction mortality: pooled results from five double-blind randomized trials. Eur Heart J 1992; 13(1): 28–32

    PubMed  CAS  Google Scholar 

  24. Harker LA, Fuster V. Pharmacology of platelet inhibitors. J Am Coll Cardiol 1986; 8 (6 Suppl. B): 21B–32B

    Article  PubMed  CAS  Google Scholar 

  25. Lewis Jr HD, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina: results of a Veterans Administration Cooperative Study. N Engl J Med 1983; 309(7): 396–403

    Article  PubMed  Google Scholar 

  26. Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone, or both in unstable angina: results of a Canadian multicenter trial. N Engl J Med 1985; 313(22): 1369–75

    Article  PubMed  CAS  Google Scholar 

  27. Theroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988; 319(17): 1105–11

    Article  PubMed  CAS  Google Scholar 

  28. Anonymous. Final report on the aspirin component of the ongoing Physicians’ Health Study: Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 1989; 321(3): 129–35

    Google Scholar 

  29. Sanmuganathan PS, Ghahramani P, Jackson PR, et al. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from metaanalysis of randomised trials. Heart 2001; 85(3): 265–71

    Article  PubMed  CAS  Google Scholar 

  30. Eccles M, Freemantle N, Mason J. North of England evidence based guideline development project: guideline on the use of aspirin as secondary prophylaxis for vascular disease in primary care. North of England Aspirin Guideline Development Group. BMJ 1998; 316(7140): 1303–9

    Article  PubMed  CAS  Google Scholar 

  31. Denninger MH, Necciari J, Serre-Lacroix E, et al. Clopidogrel antiplatelet activity is independent of age and presence of atherosclerosis. Semin Thromb Haemost 1999; 25Suppl. 2: 41–5

    CAS  Google Scholar 

  32. Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, et al. Thrombotic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases. Ann Intern Med 1998; 128(7): 541–4

    PubMed  CAS  Google Scholar 

  33. Bennett CL, Connors JM, Carwile JM, et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 2000; 342(24): 1773–7

    Article  PubMed  CAS  Google Scholar 

  34. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345(7): 494–502

    Article  PubMed  CAS  Google Scholar 

  35. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358(9281): 527–33

    Article  PubMed  CAS  Google Scholar 

  36. Bertrand ME, Rupprecht HJ, Urban P, et al. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 2000; 102(6): 624–9

    Article  PubMed  CAS  Google Scholar 

  37. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348(9038): 1329–39

    Article  Google Scholar 

  38. Hirsh J. Heparin. N Engl J Med 1991; 324(22): 1565–74

    Article  PubMed  CAS  Google Scholar 

  39. Raschke RA, Reilly BM, Guidry JR, et al. The weight-based heparin dosing nomogram compared with a “standard care” nomogram: a randomized controlled trial. Ann Intern Med 1993; 119(9): 874–81

    PubMed  CAS  Google Scholar 

  40. Spinler SA, Evans CM. Update in unfractionated heparin, low-molecular-weight heparins, and heparinoids in the elderly (age >/= 65 years). J Thromb Thrombolysis 2000; 9(1): 117

    Article  PubMed  CAS  Google Scholar 

  41. Kario K, Matsuo T, Kobayashi H. Heparin cofactor II deficiency in the elderly: comparison with antithrombin III. Thromb Res 1992; 66(5): 489–98

    Article  PubMed  CAS  Google Scholar 

  42. Campbell NR, Hull RD, Brant R, et al. Aging and heparin-related bleeding. Arch Intern Med 1996; 156(8): 857–60

    Article  PubMed  CAS  Google Scholar 

  43. The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 1990; 336(8719): 827–30

    Article  Google Scholar 

  44. Cohen M, Adams PC, Parry G, et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users: primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation 1994; 89(1): 81–8

    Article  PubMed  CAS  Google Scholar 

  45. Oler A, Whooley MA, Oler J, et al. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: a meta-analysis. JAMA 1996; 276(10): 811–5

    Article  PubMed  CAS  Google Scholar 

  46. Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337(10): 688–98

    Article  PubMed  CAS  Google Scholar 

  47. Siguret V, Pautas E, Fevrier M, et al. Elderly patients treated with tinzaparin (Innohep) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days. Thromb Haemost 2000; 84(5): 800–4

    PubMed  CAS  Google Scholar 

  48. Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: fragmin in unstable coronary artery disease study (FRIC). Circulation 1997; 96(1): 61–8

    Article  PubMed  CAS  Google Scholar 

  49. The FRAXIS Investigators. Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). Eur Heart J 1999; 20(21): 1553–62

    Article  Google Scholar 

  50. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease: efficacy and safety of subcutaneous enoxaparin in non-Q-wave Coronary Events Study Group. N Engl J Med 1997; 337(7): 447–52

    Article  PubMed  CAS  Google Scholar 

  51. Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the thrombolysis in myocardial infarction (TIMI) 11B trial. Circulation 1999; 100(15): 1593–601

    Article  PubMed  CAS  Google Scholar 

  52. Antman EM, Cohen M, Radley D, et al. Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis. Circulation 1999; 100(15): 1602–8

    Article  PubMed  CAS  Google Scholar 

  53. Eikelboom JW, Anand SS, Malmberg K, et al. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet 2000; 355(9219): 1936–42

    Article  PubMed  CAS  Google Scholar 

  54. Collet JP, Montalescot G, Lison L, et al. Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris. Circulation 2001; 103(5): 658–63

    Article  PubMed  CAS  Google Scholar 

  55. GUSTO IIb Investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes: the global use of strategies to open occluded coronary arteries (GUSTO) IIb investigators. N Engl J Med 1996; 335(11): 775–82

    Article  Google Scholar 

  56. Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. Comparison of the effects of two doses of recombinant hirudin compared with heparin in patients with acute myocardial ischemia without ST elevation: a pilot study. Circulation 1997; 96(3): 769–77

    Article  Google Scholar 

  57. Organization to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Lancet 1999; 353(9151): 429–38

    Article  Google Scholar 

  58. The Direct Thrombin Inhibitor Trialists’ Collaborative. Direct thrombin inhibitors in acute coronary syndromes: principal results of a meta-analysis based on individual patients’ data. Lancet 2002; 359(9303): 294–302

    Article  Google Scholar 

  59. Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995; 332(23): 1553–9

    Article  PubMed  CAS  Google Scholar 

  60. Topol EJ, Byzova TV, Plow EF. Platelet GPIIb-IIIa blockers. Lancet 1999; 353(9148): 227–31

    Article  PubMed  CAS  Google Scholar 

  61. Lincoff AM, Califf RM, Topol EJ. Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease. J Am Coll Cardiol 2000; 35(5): 1103–15

    Article  PubMed  CAS  Google Scholar 

  62. Simoons ML, GI-A Investigators. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet 2001; 357(9272): 1915–24

    Article  PubMed  CAS  Google Scholar 

  63. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty: The EPIC Investigation. N Engl J Med 1994; 330(14): 956–61

    Article  Google Scholar 

  64. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336(24): 1689–96

    Article  Google Scholar 

  65. The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997; 349(9063): 1429–35

    Article  Google Scholar 

  66. The EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade: evaluation of platelet IIb/IIIa inhibitor for stenting. Lancet 1998; 352(9122): 87–92

    Article  Google Scholar 

  67. Berkowitz SD, Sane DC, Sigmon KN, et al. Occurrence and clinical significance of thrombocytopenia in a population undergoing high-risk percutaneous coronary revascularization: evaluation of c7E3 for the prevention of Ischemic Complications (EPIC) Study Group. J Am Coll Cardiol 1998; 32(2): 311–9

    Article  PubMed  CAS  Google Scholar 

  68. Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol 1997; 80(4A): 11B–20B

    Article  PubMed  CAS  Google Scholar 

  69. The PRISM Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina: Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. N Engl J Med 1998; 338(21): 1498–505

    Article  Google Scholar 

  70. PRISM-Plus Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction: Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med 1998; 338(21): 1488–97

    Article  Google Scholar 

  71. Heeschen C, Hamm CW, Goldmann B, et al. Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban: PRISM Study Investigators. Platelet Receptor Inhibition in Ischemic Syndrome Management. Lancet 1999; 354(9192): 1757–62

    Article  PubMed  CAS  Google Scholar 

  72. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet Glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy. N Engl J Med 1998; 339(7): 436–43

    Article  Google Scholar 

  73. 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(25): 1879–87

    Article  PubMed  CAS  Google Scholar 

  74. Hasdai D, Holmes Jr DR, Criger DA, et al. Age and outcome after acute coronary syndromes without persistent ST-segment elevation. Am Heart J 2000; 139(5): 858–66

    Article  PubMed  CAS  Google Scholar 

  75. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA Guideline Update for the Management of Patient with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina) [online]. Available from URL: http://www.acc.org/clinicalguidelines/unstable/unstable.pdf [Accessed 2002 19 April]

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Authors and Affiliations

  1. Duke University Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA

    Manesh R. Patel &  Matthew T. Roe

Authors
  1. Manesh R. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew T. Roe
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patel, M.R., Roe, M.T. Pharmacological Treatment of Elderly Patients with Acute Coronary Syndromes without Persistent ST Segment Elevation. Drugs Aging 19, 633–646 (2002). https://doi.org/10.2165/00002512-200219090-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200219090-00002

Keywords

Search

Navigation