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ARTICLES: Y. Z. Deng, M. J. Reeves, B. S. Jacobs, G. L. Birbeck, R. U. Kothari, S. L. Hickenbottom, A. J. Mullard, S. Wehner, K. Maddox, A. Majid for the Paul Coverdell National Acute Stroke Registry Michigan Prototype Investigators IV tissue plasminogen activator use in acute stroke: Experience from a statewide registry Neurology 2006; 66: 306-312 [Abstract] [Full text] [PDF]

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IV tissue plasminogen activator use in acute stroke: Experience from a statewide registry

John M. Reid, Gordon J. Gubitz, and Stephen J Phillips, Halifax, Nova Scotia, Canada.   (3 May 2006)

Reply from the authors

Mathew J Reeves, Mathew J. Reeves, Yingzi Deng, and Julia Gargano   (3 May 2006)

IV tissue plasminogen activator use in acute stroke: Experience from a statewide registry 3 May 2006
John M. Reid, Halifax Infirmary, Nova Scotia Rm 3835 Halifax Infirmary 1796 Summer St., Halifax, Nova Scotia, Canada. B3H 3A7, Gordon J. Gubitz, and Stephen J Phillips, Halifax, Nova Scotia, Canada. Send Correspondence to journal: Re: IV tissue plasminogen activator use in acute stroke: Experience from a statewide registry johnmreid{at}doctors.net.uk John M. Reid, et al.	In their recently published study, Deng et al [1] report that almost twice as many men than women received tissue plasminogen activator (t-PA) for acute ischemic stroke (AIS, male:female ratio of 1.87). The authors state that the reasons for this are unclear but refer to a study which found that emergency physicians saw men with AIS faster than women even when stroke severity and type were controlled. [2] In our facility, we observed that among all t-PA treated AIS patients over a nine-year period (May 1996-May 2005, n=152) the male to female ratio was 1.76. This ratio was 1.06 for AIS patients who presented within 3 hours of symptom onset (i.e. those potentially eligible for t-PA treatment, n=805, p<0.01, Chi-square test). Compared with men, the women from this group had higher median stroke severity scores (7 [interquartile range 6-9] vs 7 [5-8], p<0.01, Mann Whitney test), were older (median age 79 [70-85] vs 72 [62-79] years, p<0.0001, Mann Whitney test), and had more pre-stroke disability (Oxford handicap score3 1 [0-3] vs 0 [0-2], p<0.0001, Mann Whitney test).[3] In the study by Deng et al, [1] non-treated eligible patients were older and more likely to be female than those treated with t-PA, although age was not reported by gender. Pre-stroke disability was not reported but no differences in past medical history or ambulatory status were noted. A study of thrombolysis for myocardial infarction attributed the observed preponderance of men to age rather than gender differences. [4] We propose that analysis of the influence of gender on the likelihood of receiving t-PA for AIS may be confounded by the age and pre-existing disability among the women who present to medical attention within three hours of stroke onset. This issue is worthy of further exploration because women with AIS may be more likely to benefit from t-PA than men. [5] References 1. Deng YZ, Reeves MJ, Jacobs BS, et al. IV tissue plasminogen activator use in acute stroke: experience from a statewide registry. Neurology 2006; 66:306-12. 2. Menon SC, Pandey DK, Morgenstern LB. Critical factors determining access to acute stroke care. Neurology 1998 51:427-32. 3. Phillips SJ, Eskes GA, Gubitz GJ, Queen Elizabeth II Health Sciences Centre Acute Stroke Team. Description and evaluation of an acute stroke unit. CMAJ 2002;167:655-60. 4. Williams RI, Fraser AG, West RR. Gender differences in management after acute myocardial infarction: not 'sexism' but a reflection of age at presentation. J Public Health 2004;26:259-63. 5. Kent DM, Price LL, Ringleb P, et al. Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke 2005;36:62-65.
Reply from the authors 3 May 2006
Mathew J Reeves, Michigan State University B614 West Fee Hall, East Lansing, MI 48823, Mathew J. Reeves, Yingzi Deng, and Julia Gargano Send Correspondence to journal: Re: Reply from the authors reevesm{at}msu.edu Mathew J Reeves, et al.	We thank Dr. Reid and colleagues for their interesting letter which posits that the marked gender difference in tPA treatment rates observed in our stroke registry data may be due to confounding by age and pre-existing disability. The potential for confounding by age was a concern in our study since the average age of women in the eligible population was 71.1 years, compared to 67.8 years for men (P = 0.04). However, adjustment for age did not greatly affect the odds ratio (OR) for IV tPA use. The unadjusted gender OR was 0.44, which only changed to 0.39 after adjustment for age (specified as 18-50, 51-70, 71-84, >84 years), race, arrival mode and onset to arrival time. We also examined whether specifying age as a continuous measure made a difference and it did not. Finally, we also examined the effect of gender after stratifying the data into two broad age groups (i.e., <= 70 years and >70 years). Here we found evidence of an interesting interaction effect. Among eligible subjects aged <= 70 years there was a large and statistically significant gender difference; women were 85% less likely to receive tPA treatment compared to men (OR= 0.15, 95% CI = 0.04-0.53). In contrast, among eligible subjects >70 years of age there was no gender difference (OR= 0.99, 95% CI = 0.39-2.47). We did not have access to a pre-stroke disability measure such as the Oxford handicap scale. Instead we used proxy variables such as pre-stroke ambulatory status, as well as information on past medical history including stroke, AMI, CAD, CHF, hypertension, and diabetes. A past medical history of stroke was associated with a moderately lower tPA use. However, neither it nor the other variables confounded the association between gender and tPA use when tested in our multivariable model. In our hospital-based registry, we did not find that age explained the association between gender and tPA treatment rates. However, we did find evidence of effect modification by age, with the gender difference in tPA treatment being limited to strokes <= 70 years of age. There must be other undefined factors at play. There are limited data published on the influence of gender on tPA treatment rates. More studies are necessary to examine this important issue, preferably using more detailed data on factors such as pre-stroke disability, co-morbidities, in-hospital delays, and stroke severity, that could help explain this discrepancy.