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Utilization of intravenous tissue plasminogen activator for acute ischemic stroke
Utilization of Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke
ing 325 mg of ASA with warfarin (target INR 1.4 –2.8) conducted within the Warfarin vs. Aspirin Recurrent Stroke Study (WARSS). The primary end point was a composite of all thrombo-occlusive events including recurrent ischemic stroke, TIA, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism and death from any cause in relationship to aPL positivity within each treatment arm. Results: A total of 1770 patients were in APASS with a mean age of 62.5 yrs; 42% were women; 41% were classified as aPL⫹. Cardiac disease, smoking and male gender were more often associated with aPL. After 2 yrs, recurrent stroke occurred in 11%, TIA in 5%, MI in 2% and DVT in ⬍1% of patients. The overall event rate was 22.2% among aPL⫹ and 21.8% in those aPL-negative. There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin or aspirin. There was a trend for patients with both aPL⫹ to have a higher event rate (31.7% vs. 24%, p⫽0.07). Conclusions: The presence of aPL (either LA or aCL) among patients with ischemic stroke does not predict either an increased risk for subsequent vascular occlusive events in the next 2 yrs, or a differential response to aspirin or warfarin therapy. Routine screening for aPL in patients with ischemic strokes does not appear warranted. Perspective: The frequency of aPL positivity seems excessive, suggesting the methodology was identifying nonspecific antibodies. Though the conclusions are reasonable, the study did not address several critical clinical issues: Is screening for aPL in younger persons with a stroke warranted? Would a higher INR target reduce event rates enough to justify screening? Is a longer follow-up necessary to conclude that ASA and warfarin are equivalent in patients with a stroke and aPL⫹? These are not easy questions. MR
Katzan IL, Hammer MD, Hixson ED, et al. Arch Neurol 2004;61: 346 –50. Study Question: The investigators sought to determine the rate of tissue plasminogen activator (tPA) use for stroke in the Cleveland, Ohio, community and the reasons why patients were excluded from thrombolysis treatment. Methods: The study was a retrospective cohort study and included patients admitted because of stroke to nine Cleveland Clinic Health System hospitals between June 15, 1999 –June 15, 2000. The main outcome measure was utilization of intravenous (IV) tPA and reasons for ineligibility. Results: There were 1923 admissions for ischemic stroke in the 1-year period. Of these, 288 (15.0%) arrived within the 3-hour time window, and approximately 6.9% were considered eligible for tPA. The most common reasons for exclusion among patients arriving within 3 hours were mild neurologic impairment and rapidly improving symptoms. The overall rate of tPA use among patients presenting within 3 hours was 19.4%, and the rate of use among eligible patients was 43.4% (n⫽56). The use of tPA did not differ significantly according to race or gender. Conclusions: The authors concluded that only 15% of patients arrived within the 3-hour time window for IV tPA, making delay in presentation the most common reason patients were ineligible for IV thrombolysis. Neurologic criteria were the second most common group of exclusions. Overall tPA use was low, but it was used in nearly half of all patients, with no documented contraindications. Perspective: This retrospective analysis shows that delay to emergency department presentation was the primary reason that patients with acute stroke did not receive IV tPA in the hospital system in northeastern Ohio; only 15% of patients with stroke arrived within 3 hours of symptom onset. The study provides new insights into how IV tPA for acute stroke is used in a community setting and suggests that increasing public awareness of the benefits of early presentation may significantly increase IV tPA use among patients with acute stroke. DM
Lowering Homocysteine in Patients With Ischemic Stroke to Prevent Recurrent Stroke, Myocardial Infarction, and Death. The Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled Trial Toole FJ, Malinow MR, Chambless LE, et al. JAMA 2004;291: 565–75.
Antiphospholipid Antibodies and Subsequent Thrombo-occlusive Events in Patients With Ischemic Stroke
Study Question: Do high doses of folic acid, pyridoxine (vitamin B6) and cobalamin (vitamin B12), given to reduce homocysteine levels, reduce the risk of recurrent stroke? Methods: The Vitamin Intervention for Stroke Prevention (VISP) trial consisted of 3680 adults with a nondisabling stroke in the U.S., Canada and Scotland receiving “best medical and surgical care” plus a daily vitamin. Subjects were randomly assigned within strata by age (ⱖ70 years vs. ⬍70 years) to either once-daily doses of the high-dose formulation (n⫽1827) containing 25 mg of pyridoxine, 0.4 mg of cobalamin and 2.5 mg of folic acid; or to the low-dose
The APASS Investigators. JAMA 2004;291:576 – 84. Study Question: What is the effect of baseline antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL), lupus anticoagulant (LA) or both in persons with an ischemic stroke on subsequent thrombo-occlusive events and recurrent stroke? Methods: The Antiphospholipid Antibodies and Stroke Study (APASS) is a prospective randomized study compar-
ACC CURRENT JOURNAL REVIEW May 2004
20
ing 325 mg of ASA with warfarin (target INR 1.4 –2.8) conducted within the Warfarin vs. Aspirin Recurrent Stroke Study (WARSS). The primary end point was a composite of all thrombo-occlusive events including recurrent ischemic stroke, TIA, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism and death from any cause in relationship to aPL positivity within each treatment arm. Results: A total of 1770 patients were in APASS with a mean age of 62.5 yrs; 42% were women; 41% were classified as aPL⫹. Cardiac disease, smoking and male gender were more often associated with aPL. After 2 yrs, recurrent stroke occurred in 11%, TIA in 5%, MI in 2% and DVT in ⬍1% of patients. The overall event rate was 22.2% among aPL⫹ and 21.8% in those aPL-negative. There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin or aspirin. There was a trend for patients with both aPL⫹ to have a higher event rate (31.7% vs. 24%, p⫽0.07). Conclusions: The presence of aPL (either LA or aCL) among patients with ischemic stroke does not predict either an increased risk for subsequent vascular occlusive events in the next 2 yrs, or a differential response to aspirin or warfarin therapy. Routine screening for aPL in patients with ischemic strokes does not appear warranted. Perspective: The frequency of aPL positivity seems excessive, suggesting the methodology was identifying nonspecific antibodies. Though the conclusions are reasonable, the study did not address several critical clinical issues: Is screening for aPL in younger persons with a stroke warranted? Would a higher INR target reduce event rates enough to justify screening? Is a longer follow-up necessary to conclude that ASA and warfarin are equivalent in patients with a stroke and aPL⫹? These are not easy questions. MR
Katzan IL, Hammer MD, Hixson ED, et al. Arch Neurol 2004;61: 346 –50. Study Question: The investigators sought to determine the rate of tissue plasminogen activator (tPA) use for stroke in the Cleveland, Ohio, community and the reasons why patients were excluded from thrombolysis treatment. Methods: The study was a retrospective cohort study and included patients admitted because of stroke to nine Cleveland Clinic Health System hospitals between June 15, 1999 –June 15, 2000. The main outcome measure was utilization of intravenous (IV) tPA and reasons for ineligibility. Results: There were 1923 admissions for ischemic stroke in the 1-year period. Of these, 288 (15.0%) arrived within the 3-hour time window, and approximately 6.9% were considered eligible for tPA. The most common reasons for exclusion among patients arriving within 3 hours were mild neurologic impairment and rapidly improving symptoms. The overall rate of tPA use among patients presenting within 3 hours was 19.4%, and the rate of use among eligible patients was 43.4% (n⫽56). The use of tPA did not differ significantly according to race or gender. Conclusions: The authors concluded that only 15% of patients arrived within the 3-hour time window for IV tPA, making delay in presentation the most common reason patients were ineligible for IV thrombolysis. Neurologic criteria were the second most common group of exclusions. Overall tPA use was low, but it was used in nearly half of all patients, with no documented contraindications. Perspective: This retrospective analysis shows that delay to emergency department presentation was the primary reason that patients with acute stroke did not receive IV tPA in the hospital system in northeastern Ohio; only 15% of patients with stroke arrived within 3 hours of symptom onset. The study provides new insights into how IV tPA for acute stroke is used in a community setting and suggests that increasing public awareness of the benefits of early presentation may significantly increase IV tPA use among patients with acute stroke. DM
Lowering Homocysteine in Patients With Ischemic Stroke to Prevent Recurrent Stroke, Myocardial Infarction, and Death. The Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled Trial Toole FJ, Malinow MR, Chambless LE, et al. JAMA 2004;291: 565–75.
Antiphospholipid Antibodies and Subsequent Thrombo-occlusive Events in Patients With Ischemic Stroke
Study Question: Do high doses of folic acid, pyridoxine (vitamin B6) and cobalamin (vitamin B12), given to reduce homocysteine levels, reduce the risk of recurrent stroke? Methods: The Vitamin Intervention for Stroke Prevention (VISP) trial consisted of 3680 adults with a nondisabling stroke in the U.S., Canada and Scotland receiving “best medical and surgical care” plus a daily vitamin. Subjects were randomly assigned within strata by age (ⱖ70 years vs. ⬍70 years) to either once-daily doses of the high-dose formulation (n⫽1827) containing 25 mg of pyridoxine, 0.4 mg of cobalamin and 2.5 mg of folic acid; or to the low-dose
The APASS Investigators. JAMA 2004;291:576 – 84. Study Question: What is the effect of baseline antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL), lupus anticoagulant (LA) or both in persons with an ischemic stroke on subsequent thrombo-occlusive events and recurrent stroke? Methods: The Antiphospholipid Antibodies and Stroke Study (APASS) is a prospective randomized study compar-
ACC CURRENT JOURNAL REVIEW May 2004
20