ARITS, MASH-2 findings disappoint
MedWire News: The ARTIS and MASH-2 trials have reported negative results, with disappointment for aspirin treatment during stroke thrombolysis and for magnesium treatment in patients with subarachnoid hemorrhage (SAH).
The findings were reported at the European Stroke Conference in Lisbon, Portugal.
The ARTIS (Antiplatelet Therapy in Combination with rtPA Thrombolysis in Acute Ischemic Stroke) trial tested the hypothesis that adding acute aspirin to intravenous thrombolysis would improve patient outcomes by preventing reocclusion, caused by platelet activation.
In myocardial infarction, this strategy reduces mortality, but the ARTIS investigators found that it increased rates of symptomatic intracranial hemorrhage (ICH) in stroke patients, without improving outcomes.
The investigators aimed to enroll 800 patients, but the trial was stopped because of safety concerns after inclusion of 290 patients in the aspirin group and 325 in the placebo group. Patients randomly assigned to receive aspirin were given a 300 mg intravenous dose within 90 minutes of starting thrombolysis.
In all, 4.8% of these patients versus 1.5% of those given standard treatment had symptomatic ICH, defined as at least a 4-point increase on the National Institutes of Health Stroke Scale, with ICH visible on imaging.
Furthermore, the addition of aspirin to thrombolysis did not improve patients' 3-month outcomes on the modified Rankin Scale, said Yvo Roos (Academic Medical Center, Amsterdam, the Netherlands) who presented the data.
However, he stressed that ICH rates were low in both treatment groups, "well within the range of the large registries we have and also in the range of previous thrombolysis studies."
The MASH (Magnesium in Aneurysmal Subarachnoid Hemorrhage)-2 trial did not raise any safety concerns, but also failed to show any benefits in the 1204 patients included in the trial. This was despite promising findings in the preceding MASH phase II study and in a Cochrane review, and the recognized neuroprotective properties of magnesium in conditions such as eclampsia.
The patients started treatment with intravenous magnesium sulfate 64 mmol/day or placebo within 4 days of symptom onset, continuing for up to 20 days.
The primary outcome of poor functional status at 3 months after SAH, defined as a modified Rankin Scale (mRS) score of 4 or more, occurred in 26.2% of patients given magnesium and 25.3% of those in the placebo group, which was not a significant difference. There was also no difference in rates of complete recovery (mRS=0) between the two groups, at 7.6% and 7.7%, respectively.
There was no subgroup that appeared to benefit from magnesium treatment and a meta-analysis of MASH-2 plus six previous trials showed no overall benefit.
Sanne Dorhout Mees (University Medical Center Utrecht, the Netherlands), who presented the findings, therefore concluded that magnesium therapy cannot be recommended in SAH patients.
The findings of MASH-2 are also published in The Lancet.
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By Eleanor McDermid