Current issues of ACP Journal Club are published in Annals of Internal Medicine


Prompt tissue plasminogen activator therapy increased quality of life and reduced costs in acute ischemic stroke

ACP J Club. 1998 Sep-Oct;129:52. doi:10.7326/ACPJC-1998-129-2-052

Source Citation

Fagan SC, Morgenstern LB, Petitta A, et al., and the NINDS rt-PA Stroke Study Group. Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. Neurology. 1998 Apr;50:883-90.



Is tissue plasminogen activator (t-PA), given within 3 hours of onset of symptoms, cost-effective for patients with acute ischemic stroke?


Cost-effectiveness analysis, by using Markov modeling, of data from the National Institute of Neurologic Disorders and Stroke (NINDS) rt-PA Stroke Trial.


United States.


1000 hypothetical patients assumed to be 67 years of age at the time of the incident stroke. Patients were hospitalized, and data from the NINDS rt-PA Stroke Trial were used for rates of intracerebral hemorrhage, disability at discharge and at 3-month intervals (Rankin score 0 to 5), death, discharge disposition (home, rehabilitation, or nursing home), and recurrence of stroke and death.


50% of patients received t-PA within 3 hours of symptom onset, and 50% received placebo.

Main cost and outcome measures

Quality-adjusted life-years (QALYs); disability at 7 to 10 days and at 3, 6, 9, and 12 months; and death or recurrent stroke within 1 year. The analysis was done from the perspective of the U.S. health care system and included costs for inpatient, rehabilitation, and nursing home facilities but not indirect costs, such as work loss. Costs were inflated to 1996 U.S. dollars.

Main results

Patients who received t-PA had shorter hospital stays (10.9 d vs 12.4 d, P = 0.02) and were more often discharged to their own (or a relative or friend's) home than to inpatient rehabilitation or nursing home care (48% vs 36%, P = 0.002), but more patients had symptomatic intra-cerebral hemorrhage (6% vs 1%, P < 0.05). Multivariate analysis showed that 564 (95% CI 3 to 850) QALYs would be saved over 30 years for each 1000 patients who received t-PA. The average savings per 1000 patients was $4 million (CI -$13 million to $531 billion). Sensitivity analysis showed that t-PA reduced costs 93% of the time and increased QALYs 94% of the time. The analysis also showed that the rate of intracerebral hemorrhage and death had the greatest effect on health outcomes and that length of hospitalization and annual nursing home costs had the greatest effect on costs. The cost of t-PA had minimal effect on total costs.


Tissue plasminogen activator given to patients with ischemic stroke within 3 hours of onset of symptoms was associated with shorter hospital stays, a higher proportion of patients discharged home, and increased quality-adjusted life-years.

Source of funding: National Institute of Neurologic Disorders and Stroke.

For correspondence: Dr. S.C. Fagan, Department of Pharmacy Practice, Wayne State University, 1400 Chrysler, Detroit, MI 48202, USA. FAX 313-577-5369.


Fagan and colleagues state that their results apply only when t-PA is given according to the protocol used by the NINDS rt-PA Stroke Trial investigators. This has important implications for the generalizability of the results. First, it took 38 hospitals nearly 4 years to include 624 patients (1). With the same inclusion rate, it would take these hospitals 6 years to include the 1000 patients on which the present calculations are based. In many hospitals, t-PA is routinely used, but only 5% (or less) of patients with stroke fulfill the criteria for t-PA treatment.

Second, although this trial showed unequivocal benefits, other recent trials of early thrombolytic therapy in patients with acute ischemic stroke have had more disappointing outcomes (2). A European multicenter trial showed increased early mortality caused by hemorrhage (3) but considerably better functional outcome in the t-PA group. 3 trials of streptokinase have been stopped early because of excessive intracerebral hemorrhage (3). The role of thrombolytic therapy in acute ischemic stroke is still not settled, and important differences among these studies make comparisons very difficult. In addition, publication bias may exist; at least 1 t-PA trial done by the manufacturer remains unpublished.

A strong feature of this study is sensitivity analyses, which show that t-PA treatment may save money even when the rate of symptomatic intracerebral hemorrhage is as high as 20% among treated patients (6% in the NINDS rt-PA Stroke Trial). The authors have not included indirect costs, such as work loss. The question becomes: How many more deaths caused by intracerebral hemorrhage will be accepted by us, our patients, and their families because t-PA treatment is cost-effective from a societal perspective?

Kjell Asplund, MD, PhD
University HospitalUmea, Sweden


1. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-7.

2. Wardlaw J, Yamaguchi T, del Zoppo G,Hacke W. Thrombolysis in acute ischemic stroke. In: The Cochrane Library, Issue 1, 1998. Oxford: Update Software.

3. Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995; 274:1017-25.