The Effect of Routine, Early Invasive Management on Outcome for Elderly Patients with Non–ST-Segment Elevation Acute Coronary Syndromes

  1. Richard G. Bach, MD;
  2. Christopher P. Cannon, MD;
  3. William S. Weintraub, MD;
  4. Peter M. DiBattiste, MD;
  5. Laura A. Demopoulos, MD;
  6. H. Vernon Anderson, MD;
  7. Paul T. DeLucca, PhD;
  8. Elizabeth M. Mahoney, ScD;
  9. Sabina A. Murphy, MPH; and
  10. Eugene Braunwald, MD
  1. From Washington University Medical Center, St. Louis, Missouri; Brigham and Women's Hospital, Boston, Massachusetts; Emory University, Atlanta, Georgia; Merck & Co., West Point, Pennsylvania; University of Texas Health Sciences Center, Houston, Texas; and New England Research Institutes, Watertown, Massachusetts.

    Abstract

    Background: Although increasing age is an important risk factor for adverse outcome among patients with acute coronary syndromes, elderly patients are more often managed conservatively.

    Objective: To examine outcome according to age and management strategy for patients with unstable angina and non–ST-segment elevation myocardial infarction (MI).

    Design: Randomized, controlled trial conducted from December 1997 to June 2000.

    Setting: 169 community and tertiary care hospitals in 9 countries.

    Patients: 2220 patients hospitalized with unstable angina and non–ST-segment elevation MI who were randomly assigned to an early invasive or conservative management strategy.

    Interventions: Medical therapy and coronary angiography at 4 to 48 hours versus medical therapy and predischarge exercise testing.

    Measurements: Rates of 30-day and 6-month mortality, nonfatal MI, rehospitalization, stroke, and hemorrhagic complications.

    Results: Among patients 65 years of age and older, the early invasive strategy compared with the conservative strategy yielded an absolute reduction of 4.8 percentage points (8.8% vs. 13.6%; P = 0.018) and a relative reduction of 39% in death or MI at 6 months. Outcomes of the 2 strategies were similar, however, among patients younger than 65 years of age (6.1% vs. 6.5%; P > 0.2). Among patients older than 75 years of age, the early invasive strategy conferred an absolute reduction of 10.8 percentage points (10.8% vs. 21.6%; P = 0.016) and a relative reduction of 56% in death or MI at 6 months. The additional cost per death or MI prevented with the early invasive strategy was lower for elderly patients, but major bleeding rates were higher with this strategy in patients older than 75 years of age (16.6% vs. 6.5%; P = 0.009).

    Limitations: Because this study involved patients in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy–Thrombolysis in Myocardial Infarction (TACTICS–TIMI) 18 trial, its generalizability to elderly patients with excluded comorbid conditions is unknown.

    Conclusion: Despite an increased risk for major bleeding in patients older than 75 years of age, a routine early invasive strategy can significantly improve ischemic outcomes in elderly patients with unstable angina and non–ST-segment elevation MI.

    Article and Author Information

    • Note: A list of investigators and research coordinators participating in the TACTICS–TIMI 18 study is provided in an appendix to reference 2 and is available at http://www.timi.org.

    • Grant Support: By Merck & Co.

    • Potential Financial Conflicts of Interest:Employment: P.M. DiBattiste (Merck & Co.), L.A. Demopoulos (Merck & Co.), P.T. DeLucca (Merck & Co.); Consultancies: C.P. Cannon (GlaxoSmithKline, Vertex Pharmaceuticals, Guilford Pharmaceuticals); Honoraria: W.S. Weintraub (Merck & Co.); Stock ownership or options (other than mutual funds): P.M. DiBattiste (Merck & Co.), L.A. Demopoulos (Merck & Co.), P.T. DeLucca (Merck & Co.); Grants received: R.G. Bach (Bristol-Myers Squibb, Eli Lilly & Co., Merck & Co.), C.P. Cannon (Bristol-Myers Squibb, Sanofi, Merck & Co., AstraZeneca), W.S. Weintraub (Merck & Co.), S.A. Murphy (Merck & Co.), E. Braunwald (Merck & Co.).

    • Requests for Single Reprints: Richard G. Bach, MD, Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110; e-mail, rbach{at}im.wustl.edu.

    • Current Author Addresses: Dr. Bach: Cardiovascular Division, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110.

    • Dr. Cannon: Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02482.

    • Dr. Weintraub: Emory University, Briarcliff Campus, Atlanta, GA 30322.

    • Dr. DiBattiste: AstraZeneca, 1800 Concord Pike, FOC W1-373, Wilmington, DE 19803.

    • Dr. Demopoulos: University of Pennsylvania Health System, Penn Medicine at Radnor, 250 King of Prussia Road, Radnor, PA 19087.

    • Dr. Anderson: University of Texas Health Sciences Center, 6431 Fannin Street, Houston, TX 77030.

    • Dr. DeLucca: Merck & Co., HM-209, PO Box 4, West Point, PA 19486.

    • Dr. Mahoney: New England Research Institutes, 9 Galen Street, Watertown, MA 02472.

    • Ms. Murphy: TIMI Study Group, 350 Longwood Avenue, Boston, MA 02115.

    • Dr. Braunwald: Brigham and Women's Hospital, 350 Longwood Avenue, Boston, MA 02115.

    • Author Contributions: Conception and design: R.G. Bach, C.P. Cannon, W.S. Weintraub, P.M. DiBattiste, L.A. Demopoulos, H.V. Anderson, S.A. Murphy, E. Braunwald.

    • Analysis and interpretation of the data: R.G. Bach, C.P. Cannon, W.S. Weintraub, P.M. DiBattiste, L.A. Demopoulos, H.V. Anderson, P.T. DeLucca, E.M. Mahoney, S.A. Murphy, E. Braunwald.

    • Drafting of the article: R.G. Bach, C.P. Cannon, W.S. Weintraub.

    • Critical revision of the article for important intellectual content: R.G. Bach, C.P. Cannon, W.S. Weintraub, H.V. Anderson, E.M. Mahoney, S.A. Murphy, E. Braunwald.

    • Final approval of the article: R.G. Bach, C.P. Cannon, W.S. Weintraub, H.V. Anderson, P.T. DeLucca, S.A. Murphy, E. Braunwald.

    • Provision of study materials or patients: R.G. Bach, C.P. Cannon.

    • Statistical expertise: C.P. Cannon, W.S. Weintraub, P.T. DeLucca, E.M. Mahoney, S.A. Murphy.

    • Obtaining of funding: C.P. Cannon, W.S. Weintraub, P.M. DiBattiste, L.A. Demopoulos, E. Braunwald.

    • Administrative, technical, or logistic support: C.P. Cannon, W.S. Weintraub, P.M. DiBattiste, E. Braunwald.

    • Collection and assembly of data: R.G. Bach, C.P. Cannon, W.S. Weintraub, S.A. Murphy.

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