Intravenous Recombinant XXXX Does Not Impact Mortality in Acute @entity385 at Any Time Point up to 6 Months: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

@entity1 @entity64 @entity1456 @entity385
BACKGROUND AND OBJECTIVE: Concerns about the harms of intravenous alteplase (recombinant @entity1456 ) continue to deter physicians from treating @entity1 with acute @entity385 with the only drug proven to positively impact outcomes and reduce disability. Recent literature indicates an increase in mortality with alteplase within 7 days, an effect that does not persist from 3 months onwards. The objective of this meta-analysis was to pool mortality estimates from randomized controlled clinical trials (RCTs) at 7 days, 30 days, 90 days, and 6 months after @entity64 onset. METHODS: PubMed, Embase, Scopus, CENTRAL, and clinicaltrials.gov were searched through to April 2014, using "hedges" for @entity1456 , acute @entity385 , and placebo. Two independent authors abstracted data and assessed study quality. Data were pooled using Dersimonian and Laird's random effects model. RESULTS: Eleven RCTs (n = 6905) were included in the final analysis. Two authors independently performed study selection and data abstraction. There was no publication bias and total variance attributable to heterogeneity was not significant (I(2) < 50%) at any time point. There was no difference in mortality between alteplase and placebo groups at any time point. Trials that randomized @entity1 beyond 3 h (excluded @entity1 within the 3-h window) did not drive the mortality difference seen at any time point. Exclusion sensitivity analysis revealed that exclusion of the NINDS trial rendered the 7-day difference significant towards increased mortality with alteplase. Quality adjustment did not alter the results. CONCLUSION: Intravenous alteplase did not impact mortality in @entity1 with acute @entity385 at any of the measured time points up to 6 months (i.e., there was no increase in the risk of death with alteplase). Therefore, intravenous alteplase should be given to all eligible @entity1 with acute @entity385 to improve long-term neurologic outcomes. The effects of alteplase on early survival are more complex than previously understood.
