Adding low-dose methylprednisolone therapy to endovascular treatment of acute ischemic stroke did not significantly improve the degree of overall disability in a new randomized study. However, there were some other potentially positive effects that could justify further investigation.
The MARVEL study was presented at the International Stroke Conference 2024, which is taking place this week in Phoenix, Arizona. The study was also published online in JAMA on February 8th.
Led by Wenjie Zi, MD, and Fengli Li, MD, of Neurology at Army Medical University in Chongqing, China, the authors noted that preclinical models suggested potential benefits of corticosteroids in stroke treatment, including reducing infarct size and regulating brain blood flow, stabilizing the blood-brain barrier, preventing angiogenic edema, inhibiting lipid peroxidation induced by free radicals, and modulating the immune response. However, none of these potential effects have been validated in clinical studies.
Previous studies investigating corticosteroids in stroke treatment were mostly conducted before the advent of thrombectomy as a viable treatment option and under the more challenging conditions of permanent, as opposed to transient, cerebral ischemia. They also identified the presence or absence of reperfusion as a crucial factor for the effectiveness of corticosteroids in animal models.
The current study aimed to determine the effects of intravenously administered low-dose methylprednisolone in patients with acute ischemic stroke due to large vessel occlusion within the context of rapid cerebral reperfusion achievable through endovascular treatment.
The MARVEL study, conducted in 82 hospitals in China, included 1680 patients with stroke and proximal intracranial large vessel occlusion who presented within 24 hours after their last known well state. They were randomly assigned to receive three days of intravenous methylprednisolone (2 mg/kg/day) or placebo in addition to endovascular thrombectomy.
The primary endpoint, degree of disability at 90 days measured by the overall distribution of scores on the modified Rankin Scale (mRS), did not significantly differ between the two groups. The mean 90-day mRS score was 3 in both groups, and the adjusted generalized odds ratio for a lower degree of disability in the methylprednisolone group was 1.10 (95% CI 0.96–1.25; P = .17).
Primary safety outcomes included mortality at 90 days and occurrence of symptomatic intracranial hemorrhage within 48 hours. The methylprednisolone group had a lower mortality rate (23.2% vs. 28.5%; adjusted risk ratio 0.84; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs. 11.7%; adjusted risk ratio 0.74; P = .04) compared to the placebo group.
In addition, the secondary endpoint of a mRS score of 0–4 at 90 days occurred in 71.5% of the methylprednisolone group and 66.2% of the placebo group, which corresponds to an adjusted relative risk of 1.07 (95% CI: 1.00–1.14; P = .04).
The authors noted that the study „provides new insights into the effects of corticosteroids in stroke therapy when used as an adjunct to endovascular therapy.“
They emphasized that in the current guidelines of the American Heart Association/American Stroke Association, the use of conventional or high doses of Methylprednisolone is recommended to be avoided due to insufficient efficacy and potential increased risk of infectious complications.
However, in this study, low-dose methylprednisolone was associated with lower mortality, a lower rate of symptomatic intracranial hemorrhage, and fewer cases of pneumonia. They reported similar effects of low-dose corticosteroids in preventing hospital-acquired pneumonia in patients with traumatic brain injury and patients with severe community-acquired pneumonia.
„Therefore, to our knowledge, this study is one of the first to provide evidence for the potential role of corticosteroid therapy in endovascular stroke reperfusion,“ they commented.
The researchers suggested that although the primary endpoint was neutral, the secondary endpoint of a higher proportion of patients in the methylprednisolone group alive and not bedridden at 90 days (mRS score 0–4) indicates that corticosteroid therapy has the potential to increase the percentage of patients with an outcome that does not require constant care.
They said that the finding of reduced symptomatic intracranial hemorrhage supports the stabilization of the blood-brain barrier as a potential positive effect of methylprednisolone.
In an accompanying editorial, James E. Siegler, MD, and Shyam Prabhakaran, MD, of the University of Chicago, recognized the survival advantage in the steroid group in favor of moderate disability but noted that it was unclear why this did not translate into a favorable shift in the overall distribution of 90-day mRS scores.
„Perhaps the lower mortality without a significant improvement in functional independence is due to the decreased risk of pneumonia with steroid use,“ they speculated.
The editors added that corticosteroids also have potential benefits for supporting blood flow and reducing cytotoxic or vasogenic brain edema after a large cerebral infarction.
„In general, the results of the MARVEL randomized clinical trial complement the literature that points to the lack of effectiveness of additional corticosteroids in acute ischemic stroke. However, the secondary analyzes of this study suggest a potential survival benefit that could be mediated through a reduction in cytotoxic or vasogenic edema after a malignant infarction,“ the editorial concluded, adding that these results justify further investigation.
However, they also noted that in this study, the steroid group had twice the risk of new-onset diabetes (4.8% vs. 2.9%), which in their opinion is cause for concern and may potentially diminish or counteract any neuroprotective effects.
„This study was supported by the National Natural Science Foundation of China, the Chongqing Science and Health Joint Project, and the National Natural Science Foundation of China Major Program. Zi and Li reported no relevant disclosures; disclosures for co-authors appeared in the paper. Prabhakaran reported receiving grants from the National Institutes of Health and the Agency for Healthcare Research and Quality as well as personal fees from UpToDate. Siegler made no disclosures.“