Time trends in systemic thrombolysis in a large hospital-based stroke registry

Background: Systemic thrombolysis for acute stroke was approved by German authorities in 2002. While recombinant tissue plasminogen activator (rtPA) use first remained low, systemic thrombolysis is nowadays an established part of common stroke care. The purpose of this study was to determine changes in systemic thrombolysis rates within an observation period of 7 years following the approval of rtPA therapy in Germany in a large state-wide stroke data set.

Methods: We analyzed a prospective hospital-based stroke registry covering the entire federal state of Hesse, Germany. All hospitals providing stroke care in Hesse (neurology hospitals and hospitals for internal medicine) are obligated to register all inpatients. All cases admitted between 2003 and 2009 with a final diagnosis of ischemic stroke (ICD-10: I63) were selected. We analyzed the relationship between thrombolysis rates, onset-to-admission time (hospital arrival ≤3 and >3 h after symptom onset), patient age (quartiles and dichotomized in ≤80 and >80 years) and disability at admission (assessed by the Rankin Scale). A one-way ANOVA with Bonferroni correction for multiple comparisons was performed to test for significant changes during the observation period.

Results: 88,340 patients with ischemic stroke were identified. Thrombolysis rates increased continuously from 2.5% in 2003 to 8.4% in 2009. In patients admitted within 3 h after symptom onset, the thrombolysis rate was 2.5-fold higher in 2009 (25.4%) as compared to 2003 (10.5%). The mean age (±SD) of thrombolyzed patients increased from 68.7 (±11.5) years in 2003 to 70.7 (±13.4) years in 2009 (p for trend = 0.014), but remained stable in the entire cohort. 20.1% of all systemic thrombolytic treatments were performed in patients >80 years old. Disability at admission decreased more pronouncedly in rtPA-treated patients (Rankin Scale score 0-2: 15.2% in 2003 and 24.5% in 2009; p for trend <0.001) as compared to the entire cohort (34.5% in 2003 and 41.5% in 2009; p for trend <0.001).

Conclusions: Thrombolytic therapy is increasingly used in acute stroke, particularly in patients admitted within the 3-hour time window. Higher treatment rates are at least partially explained by spreading rtPA application, including older and less severely affected patients. Approximately one fifth of all rtPA treatments were given to the very old (>80 years), which is outside the age limit for rtPA approval. In the light of upcoming demographic changes, the proportion of very aged stroke patients will increase substantially, further tightening the current discussion of an upper age limit for thrombolytic therapy.