Researchers conducting an observational study of participants in randomized stroke trials have concluded that many stroke patients for whom thrombolysis is contraindicated may benefit from the treatment. The study was published online Feb. 6 in Stroke.
Benedikt Frank, MD, of the department of neurology at the University of Glasgow, Scotland, and colleagues noted that the “sole effective and approved drug” to treat ischemic stroke is available to a minority of stroke patients because of the limited therapeutic time window and the many contraindications to thrombolytic therapy. However, the researchers asserted that the contraindications were based primarily on exclusion and inclusion criteria used in randomized trials, and that these criteria often were the result of expert opinion rather than data.
Frank et al used the Virtual International Stroke Trials Archive (VISTA), which contains information on patients whose treatments were decided outside of original trial inclusion and exclusion criteria, to evaluate the benefit or harm of treating stroke patients with alteplase when contraindications to thrombolytic therapy existed. They looked at records of patients who had participated in ischemic stroke trials between 1998 and 2008.
They searched the database for patients who had contraindications to thrombolysis due to age or medical history, hemostasis, glucose/blood pressure, CT findings or National Institutes of Health Stroke Score (NIHSS). The primary outcome measure of the current study was the distribution of modified Rankin Scale (mRS) at 90 days post-event. The database contained 90-day mRS for 9,613 patients, of whom 6,231 had either at least one known contraindication or warning for treatment with alteplase.
The results indicated that patients aged over 80 have an odds ratio of 1.4 of benefiting from alteplase treatment, and that patients with prior stroke and diabetes mellitus also benefited, with an odds ratio of 1.5.
Patients taking single antiplatelet drugs benefited with an odds ratio of 1.42, but patients taking dual antiplatelet therapy did poorly after treatment with alteplase, with a 0.8 odds ratio of benefiting from the treatment and the highest rate of intracerebral hemorrhage (ICH) among all the patients receiving thrombolysis.
The authors pointed out that although ischemic stroke patients who have taken oral anticoagulants are excluded from alteplase, the American Heart Association/American Stroke Association guidelines recommend treatment even if oral coagulation has been taken provided the International Normalized Ratio (INR) is below 1.7. They further recommended not delaying treatment to wait for test results if the patient has no suspected blood abnormality. The findings in the current study support the relaxed guidelines, as the odds ratios supported alteplase treatment for patients who have taken oral anticoagulants (1.32) with INR less than or equal to 1.7 (2.20), and INR greater than 1.7 (1.21).
“Although in most subgroups of patients with disturbed hemostasis, rates of ICH were higher in thrombolized patients, OR [odds ratio] point estimates for our primary outcome favor alteplase treatment,” the authors wrote. They added that this finding has implications for several ongoing trials of combinations of thrombolysis with anticoagulants.
The researchers noted that the odds ratios favored treating patients with elevated glucose levels, but they urged caution when treating patients with high systolic blood pressure, remarking that although the odds ratios indicated significant benefit to these patients, the rates of ICH increased when these patients were thrombolized.
Frank et al found no reason to exclude patients with CT findings or NIHSS of greater than 22. The researchers indicated that the subgroup of patients with NIHSS of less than 6 was small, and so they could not confirm a benefit to alteplase treatment in these patients.
The authors acknowledged that theirs was an observational study and selection bias was inevitable, but they also pointed out that all patients in the VISTA database were participants in randomized trials, and therefore careful protocol and follow-up were observed. They noted also that more nonthrombolized patients were enrolled earlier in time, and therefore standards of care may have been better for the thrombolized patients, who had a later average date of enrollment.