Log in to MyACC
Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis
Study Questions:
What is the overall effect of intravenous recombinant tissue plasminogen activator (rt-PA) when given up to 6 hours after stroke for important early and late outcomes?
Methods:
The investigators searched for randomized trials of intravenous rt-PA versus control given within 6 hours of onset of acute ischemic stroke up to March 30, 2012. They estimated summary odds ratios (ORs) and 95% confidence intervals (CIs) in the primary analysis for prespecified outcomes within 7 days and at the final follow-up of all patients treated up to 6 hours after stroke.
Results:
In up to 12 trials (7,012 patients), rt-PA given within 6 hours of stroke significantly increased the odds of being alive and independent (modified Rankin Scale [mRS], 0-2) at final follow-up (1,611/3,483 [46.3%] vs. 1,434/3,404 [42.1%]; OR, 1.17; 95% CI, 1.06-1.29; p = 0.001), absolute increase of 42 (19-66) per 1,000 people treated, and favorable outcome (mRS, 0-1) absolute increase of 55 (95% CI, 33-77) per 1,000. The benefit of rt-PA was greatest in patients treated within 3 hours (mRS, 0-2; 365/896 [40.7%] vs. 280/883 [31.7%]; 1.53; 1.26-1.86; p < 0.0001), absolute benefit of 90 (46-135) per 1,000 people treated, and mRS 0-1 (283/896 [31.6%] vs. 202/883 [22.9%]; 1.61; 1.30-1.90; p < 0.0001), absolute benefit 87 (46-128) per 1,000 treated. Numbers of deaths within 7 days were increased (250/2,807 [8.9%] vs. 174/2,728 [6.4%]; 1.44; 1.18-1.76; p = 0.0003), but by final follow-up the excess was no longer significant (679/3,548 [19.1%] vs. 640/3,464 [18.5%]; 1.06; 0.94-1.20; p = 0.33). Symptomatic intracranial hemorrhage (272/3,548 [7.7%] vs. 63/3,463 [1.8%]; 3.72; 2.98-4.64; p < 0.0001) accounted for most of the early excess deaths. Patients older than 80 years achieved similar benefit to those ages 80 years or younger, particularly when treated early.
Conclusions:
The authors concluded that intravenous rt-PA increased the proportion of patients who were alive and independent at final follow-up.
Perspective:
This systemic review suggests that intravenous rt-PA increased the proportion of patients who were alive with favorable outcome and alive and independent at final follow-up. The analysis strengthens previous evidence to treat patients as early as possible after acute ischemic stroke, although some patients might benefit up to 6 hours after stroke. The key message from contemporary trials and the meta-analysis is that many eligible patients from subgroups excluded by the current drug labeling may benefit from rt-PA. Every stroke patient should, therefore, be evaluated as a candidate for thrombolysis and managed as a medical emergency irrespective of age, severity, and clinical presentation.
Keywords: Thrombolytic Therapy, Stroke, Intracranial Hemorrhages, Follow-Up Studies, Cardiology, Cardiovascular Diseases, Fibrinolytic Agents, Tissue Plasminogen Activator
< Back to Listings
