Boston, MA -- More and more heart attack patients are getting thrombolytic therapy as a result of studies showing the clot-busting drugs can reduce the risk of dying. But a new study led by Harvard Medical School researchers adds to the growing body of evidence that thrombolytic drugs may increase the overall risk of death for some patients, particularly the oldest and those with certain medical conditions or histories. The results suggest that national guidelines on the use of these drugsæsuch as streptokinase and tissue plasminogen activator (t-PA)æshould be applied with greater selectivity, and possibly revised, to maximize benefit and minimize risk due to bleeding or stroke, said lead author Stephen Soumerai, professor of ambulatory care and prevention at Harvard Medical School and Harvard Pilgrim Health Care. Co-authors of the article, which appears in the March 11 Archives of Internal Medicine, include two of Soumerai’s colleagues in the HMS/HPHC Department of Ambulatory Care and Prevention, assistant professor Thomas McLaughlin and associate professor Dennis Ross-Degnan, along with collaborators from Boston University School of Public Health and the University of Massachusetts Medical School. The study was funded by the National Institute on Aging of the National Institutes of Health.
The researchers examined records of 2,659 patients with acute myocardial infarction admitted to 37 Minnesota community hospitals from 1992 to 1996. Of this group, 719 patients were eligible for thrombolytic therapy according to the guidelines, which rely on time from symptom onset (under 12 hours), electrocardiograph readings, and absence of contraindications such as trauma, bleeding, or extremely high blood pressure.
In the study, about 63 percent of eligible patients and 14 percent of ineligible patients received the drugs. Thrombolytic therapy was associated with reduced mortality among eligible patients younger than 80 years, but with increased mortality in older patients. Among eligible patients 80 to 90 years old, those who got the drugs had an estimated 40 percent greater risk of death in the hospital compared with patients who did not receive the drugs. For ineligible patients, use of the drugs increased the risk of death regardless of age. For the entire patient group (age 65-plus), the risk of death associated with thrombolytic therapy rose 4 percent for each year of age.
There are several reasons why elderly patients may not share the benefits of thrombolytic therapy seen in younger patients. The elderly are more likely to have contraindications, their risks for bleeding and stroke are markedly increased, and they tend to experience longer delays between symptom onset and hospitalization that substantially reduce the drugs’ effect on survival. Thirty-eight percent of the patients in the study who got thrombolytic therapy had contraindications. This suggests that heart attack patients in typical practice settings are not as carefully selected for thrombolytic therapy as patients in trials areæa problem that commonly frustrates the smooth transition of treatments from clinical trials into community practice.
"The oldest patients, even those without contraindications to therapy, experienced an excess risk of mortality compared with untreated patients," the authors write. "Findings of this study suggest a need to re-assess our approach to the use of thrombolytic therapy in the treatment of acute myocardial infarction patients older than 75 years."
A study from John Hopkins University, published in the May 16, 2000 Circulation, produced similar results: patients over age 75 who got thrombolytic drugs were nearly 40 percent more likely to die within 30 days than patients not receiving the drugs.
"Many doctors have been hesitant to prescribe thrombolytic therapy for the oldest patients with myocardial infarction, despite guidelines that strongly promote the therapy for patients of all ages," Soumerai said. "Our findings, along with those of the earlier study, really seem to justify their concerns." The authors recommend that alternative treatments for elderly patients, such as primary coronary angioplasty, be further evaluated.
Materials provided by Harvard Medical School. Note: Content may be edited for style and length.
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