Should Thrombolytic Therapy Be Used in Patients Older Than Age 80?
Abstracts & Commentary
By John J. Caronna, MD, Vice-Chairman, Department of Neurology, Cornell University Medical Center, Professor of Clinical Neurology, NewYork-Presbyterian Hospital. Dr. Caronna reports no financial relationship relevant to this field of study.
This article originally appeared in the May 2006 issue of NA. It was reviewed by Matthew E. Fink, MD, and peer reviewed by M. Flint Beal, MD. Dr. Fink is Vice Chairman, Professor of Clinical Neurology, Weill Cornell Medical College; Chief of Division of Stroke and Critical Care Neurology, NewYork-Presbyterian Hospital. Dr. Beal is Professor and Chairman, Department of Neurology, Cornell University Medical College. Drs. Fink and Beal report no financial relationship relevant to this field of study.
Synopsis: The results of this study underline the uncertainty regarding the risk/benefit ratio of rtPA treatment in acute stroke in patients older than 80 years of age.
Sources: van Oostenbrugge RJ, et al. Thrombolysis for Acute Stroke with Special Emphasis on the Very Old: Experience from a Single Dutch Centre. J Neurol Neurosurg Psychiatry. 2006;77:375-377; Schwark C, Schellinger PD. Is Old Age Really a Reason to Withhold Thrombolytic Therapy? J Neurol Neurosurg Psychiatry. 2006;77:289.
Intravenous recombinant tissue plasminogen activator (rtPA) is the only evidence-based specific treatment currently available for acute ischemic stroke. rtPA improved outcome in the NINDS Trial,1 but it is unclear what the risk/benefit ratio is in very old patients. Therefore, van Oostenbrugge and colleagues sought to describe their clinical experience in 184 consecutive first-ever rtPA-treated patients at a single Dutch medical center. There was no upper age limit for eligibility. Stroke severity was assessed using the NIH stroke scale (NIHSS). There were no significant differences in stroke risk factors between the under and over age 80 years groups. Demographic data and time-to-treatment are tabulated (see Table 1).
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Outcome was defined as favorable if the modified Rankin scale (mRs) score at 3 months was 0 to 1, and good outcome, functional independence, if the mRs score was < 2.
Seventy-four patients (40%) had a favorable outcome and 104 (57%) had a good outcome. Outcome at 3 months was related to age (see Table 2). Sixty-two (45%) patients < 80 years of age but only 12 (27%) patients > 80 years of age had a favorable outcome. The corresponding figures for good outcome were 88 (63%) and 16 (36%), respectively. The differences are statistically significant for both favorable and good outcomes.
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Symptomatic intracerebral hemorrhage (SICH) occurred in 9 patients (5%), of whom 8 died. NIHSS scores and time-to-treatment were not significantly different in this group. Four patients (3%) with SICH were < 80 years of age and 5 (11%) were > 80 years of age. In 3 of 5 patients > 80 years of age, SICH occurred in areas not affected by acute infarction. In patients < 80 years of age, SICH occurred only in infarcted brain tissue.
Commentary
van Oostenbrugge et al found a significantly worse outcome as measured by the mRS in patients older than 80 years of age compared to younger patients. The higher frequency of poor outcome in older patients could not be attributed to differences in baseline characteristics that are associated with worse outcomes, such as pretreatment hypertension, higher NIHSS score, or longer time-to-treatment. They found, as have others,2 that besides stroke severity and preexisting disability, age is a strong and independent predictor of stroke prognosis.
van Oostenbrugge et al also found a non-significant trend towards more intracranial bleeding in older patients treated with rtPA. Therefore, they remain uncertain whether rtPA should be used in stroke patients over 80 years of age.
Schwark and Schellinger in an editorial commentary have no such uncertainty. Although they concede that older patients do have a higher risk of not recovering from ischemic stroke, they point out that this risk is not reduced by withholding thrombolytic therapy. The elderly have a higher risk of complications from thrombolytic therapy. Therefore, physicians wishing to do no harm often do nothing at all. Schwark and Schellinger exhort physicians to take action and not to fear use of thrombolytics. They quote Arnold Schwarzenegger, "Fear is not an option" (from the film True Lies, 1994), but stop short of calling van Oostenbrugge and colleagues "girlie men."
Schwark and Schellinger agree that old age per se is not a contraindication to thrombolytic therapy in the elderly, until data from further randomized clinical trials indicate otherwise.
References
1. Tissue Plasminogen Activator for Acute Ischemic Stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581-1587.
2. Kammersgaard LP, et al. Short- and Long-Term Prognosis for Very Old Stroke Patients. The Copenhagen Stroke Study. Age Ageing. 2004;33:149-154.
The results of this study underline the uncertainty regarding the risk/benefit ratio of rtPA treatment in acute stroke in patients older than 80 years of age.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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