USE OF TISSUE-TYPE PLASMINOGEN ACTIVATOR FOR ACUTE ISCHEMIC STROKE: THE CLEVELAND AREA EXPERIENCE.

Katzan IL, et al. JAMA 2000 Mar 1;283(9):1151-8.

CONTEXT: Little is known regarding outcomes after intravenous tissue-type plasminogen activator (IV tPA) therapy for acute ischemic stroke outside a trial setting.

OBJECTIVE: To assess the rate of IV tPA use, the incidence of symptomatic intracerebral hemorrhage (ICH), and in-hospital patient outcomes throughout a large urban community.

DESIGN: Historical prospective cohort study conducted from July 1997 through June 1998.

SETTING: Twenty-nine hospitals in the Cleveland, Ohio, metropolitan area.

PATIENTS: A total of 3948 patients admitted to a study hospital with a primary diagnosis of ischemic stroke (International Classification of Diseases, Ninth Revision, Clinical Modification code 434 or 436).

MAIN OUTCOME MEASURES: Rate of IV tPA use and occurrence of symptomatic ICH among patients treated with tPA; proportion of patients receiving tPA whose treatment deviated from national guidelines; in-hospital mortality among patients receiving tPA compared with that among ischemic stroke patients not receiving tPA and with mortality predicted by a model.

RESULTS: Seventy patients (1.8%) admitted with ischemic stroke received IV tPA. Of those, 11 patients (15.7%; 95% confidence interval [CI], 8.1%-26.4%) had a symptomatic ICH (of which 6 were fatal) and 50% (95% CI, 37.8%-62.2%) had deviations from national treatment guidelines. In-hospital mortality was significantly higher among patients treated with tPA (15.7%) compared with patients not receiving tPA (5.1%, P<.001) and compared with the model's prediction (7.9%; P<.006).

CONCLUSIONS: A small proportion of patients admitted with acute ischemic stroke in Cleveland received tPA; they experienced a high rate of ICH. Cleveland community experience with tPA for acute ischemic stroke may differ from that reported in clinical trials.

COMMENT: This study demonstrates that the effectiveness of thrombolytics for CVA in the community setting is less than desirable with a higher incidence of ICH.

INTRAVENOUS TISSUE-TYPE PLASMINOGEN ACTIVATOR THERAPY FOR ISCHEMIC STROKE: HOUSTON EXPERIENCE 1996 TO 2000.

Grotta JC, et al. Arch Neurol 2001 Dec;58(12):2009-13.

CONTEXT: Intravenous tissue-type plasminogen activator (tPA) therapy using the National Institute of Neurological Disorders and Stroke criteria has been given with variable safety to less than 5% of the patients who have ischemic strokes nationwide. Our center is experienced in treating large numbers of stroke patients with intravenous tPA.

OBJECTIVE: To report our total 4-year experience in the treatment of consecutive patients who had an ischemic stroke.

DESIGN: Prospective inception cohort registry of all patients seen by our stroke team and an additional retrospective medical record review of all patients treated between January 1, 1996, and June 1, 2000.

SETTING: A veteran stroke team composed of fellows and stroke-specialty faculty servicing 1 university and 3 community hospitals in a large urban setting.

PATIENTS: Consecutive patients with ischemic stroke treated within the first 3 hours of symptom onset.

INTERVENTION: According to the National Institute of Neurological Disorders and Stroke protocol, 0.9 mg/kg of intravenous tissue-type plasminogen activator was administered.

MAIN OUTCOME MEASURES: Number and proportion treated, patient demographics, time to treatment, hemorrhage rates, and clinical outcome.

RESULTS: A total of 269 patients were treated between January 1, 1996, and June 1, 2000. Their mean age was 68 years (age range, 24-93 years); 48% were women. This represented 9% of all patients admitted with symptoms of cerebral ischemia at our most active hospital (over the final 6 months, 13% of all patients with symptoms of cerebral ischemia and 15% of all acute ischemic stroke patients). Before treatment the mean +/- SD National Institutes of Health Stroke Scale (NIHSS) score was 14.4 +/- 6.1 points (median, 14 points; range, 4-33 points). A tPA bolus was given at 137 minutes (range, 30-180 minutes); 28% of the patients were treated within 2 hours. The mean door-to-needle time was 70 minutes (range, 10-129 minutes). The symptomatic intracerebral hemorrhage rate was 5.6% of those patients with a second set of brain scans (4.5% of all patients), with a declining trend from 1996 to 2000. Protocol violations were found in 13% of all patients; the symptomatic intracerebral hemorrhage rate in these patients was 15%. At 24 hours, the NIHSS score was 10 +/- 8 points (median, 8 points; range, 0-36 points). In-hospital mortality was 15% and the patients' discharge NIHSS scores were 7 +/- 7 points (median, 3 points; range, 0-35 points).

CONCLUSIONS: Intravenous tPA therapy can be given to up to 15% of the patients with acute ischemic stroke with a low risk of symptomatic intracerebral hemorrhage. Successful experience with intravenous tPA therapy depends on the experience and organization of the treating team and adherence to published guidelines.

COMMENT: This paper, at first glance, shows an apparent successful community experience in Houston. However, upon closer inspection, this paper involved only four Houston hospitals, using a stroke team that participated in the NINDS trial.

THROMBOLYSIS FOR ACUTE STROKE IN ROUTINE CLINICAL PRACTICE.

Bravata DM, et al. Arch Intern Med 2002 Sep 23;162(17):1994-2001

BACKGROUND: Studies have demonstrated that thrombolytic therapy for acute stroke can be given safely and effectively in study settings with experienced clinicians, but the patient outcomes associated with thrombolytic therapy in routine clinical practice require investigation.

OBJECTIVES: To compare outcomes among patients given intravenous thrombolysis in routine clinical practice with the results of the National Institute of Neurological Disorders and Stroke rt-PA Study (NINDS cohort) and to examine whether protocol deviations are associated with adverse events.

METHODS: Retrospective cohort of community-based patients given thrombolysis for acute stroke from May 1, 1996, through December 31, 1998, in 16 Connecticut hospitals (Connecticut cohort).

RESULTS: Forty-two (67%) of 63 patients in the Connecticut cohort had at least 1 major protocol deviation, and 61 (97%) had major or minor protocol deviations. Overall, the in-hospital mortality was higher in the Connecticut cohort (16/63 [25%]) compared with the NINDS cohort (40/312 [13%]; P =.01). The serious extracranial hemorrhage rate was also higher for the Connecticut cohort (8/63 [13%] vs 5/312 [2%]; P =.001). Patients in the Connecticut cohort without major protocol deviations had outcomes similar to those in the NINDS cohort; however, patients in the Connecticut cohort with major protocol deviations had higher rates of in-hospital mortality (13/42 [31%] vs 40/312 [13%]; P =.002) and serious extracranial hemorrhage (7/42 [17%] vs 5/312 [2%]; P =.001).

CONCLUSIONS: Protocol deviations occur commonly when thrombolytic therapy is given to stroke patients in routine clinical practice. Patients who receive thrombolysis with major protocol deviations have higher rates of in-hospital mortality and serious extracranial hemorrhage than patients in the NINDS cohort.

COMMENT: This last paper is another effectiveness study, demonstrating a higher incidence of protocol violation & mortality in the real-world setting.

FREQUENCY OF THROMBOLYTIC THERAPY IN PATIENTS WITH ACUTE ISCHEMIC STROKE AND THE RISK OF IN-HOSPITAL MORTALITY

Heuschmann, PU, et al. Stroke. 2003 May;34(5):1106-13.

BACKGROUND AND PURPOSE: There is little information about early outcome after intravenous application of tissue-type plasminogen activator (tPA) for stroke patients treated in community-based settings. We investigated the association between tPA therapy and in-hospital mortality in a pooled analysis of German stroke registers.

METHODS: Ischemic stroke patients admitted to hospitals cooperating within the German Stroke Registers Study Group (ADSR) between January 1, 2000, and December 31, 2000, were analyzed. The ADSR is a network of regional stroke registers, combining data from 104 academic and community hospitals throughout Germany. Patients treated with tPA were matched to patients not receiving tPA on the basis of propensity scores and were analyzed with conditional logistic regression. Analyses were stratified for hospital experience with the administration of tPA.

RESULTS: A total of 13 440 ischemic stroke patients were included. Of these, 384 patients (3%) were treated with tPA. In-hospital mortality was significantly higher for patients treated with tPA compared with patients not receiving tPA (11.7% versus 4.5%, respectively; P<0.0001). After matching for propensity score, overall risk of inpatient death was still increased for patients treated with tPA (odds ratio [OR], 1.7; 95% CI, 1.0 to 2.8). Patients receiving tPA in hospitals that administered 5 thrombolytic therapies in 2000 had an increased risk of in-hospital mortality (OR, 3.3; 95% CI, 1.1 to 9.9). No significant influence of tPA use for risk of inpatient death was found in hospitals administering >5 thrombolytic treatments per year (OR, 1.3; 95% CI, 0.8 to 2.4).

CONCLUSIONS: In-hospital mortality of ischemic stroke patients after tPA use varied between hospitals with different experience in tPA treatment in routine clinical practice. Our study suggested that thrombolytic therapy in hospitals with limited experience in its application increase the risk of in-hospital mortality.