MOST Trial Findings Indicate Need for Improved Thrombolysis in Ischemic Stroke Treatment

Overview of the MOST Trial

The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was a significant study aimed at evaluating the efficacy of adjunctive thrombolysis with two specific blood thinners, argatroban and eptifibatide, for acute ischemic stroke. The trial, which was conducted at 57 hospitals in the United States from October 2019 through July 2023, included 514 adults with a pre-thrombolysis National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater. However, the trial was halted early after the first 500 enrolled patients did not show improvement, indicating a need for further research and improvement in thrombolysis.

The Findings of the MOST Trial

Contrary to expectations, the MOST trial found that placebo yielded the best 90-day utility weighted modified Rankin Scale (mRS) scores. Both argatroban and eptifibatide contributed to risk without boosting efficacy. The probability of argatroban and eptifibatide being better than placebo was very low, easily meeting the futility threshold. This indicates that neither of the blood thinners improved outcomes among the stroke survivors, with argatroban even showing significantly higher all-cause mortality rates than placebo.

Analyzing Safety Outcomes

In terms of safety outcomes, argatroban was significantly more common than placebo in terms of all-cause mortality. Furthermore, intracerebral hemorrhage rates trended in the wrong direction with both adjuncts. While neither argatroban nor eptifibatide significantly increased the risk of bleeding into the brain, they also failed to improve outcomes in stroke survivors, leading to the trial being stopped early due to futility.

Limitations and Future Directions

The MOST trial, like all clinical trials, had its limitations. The single-blind design and the unknown impact of adjunctive intra-arterial antithrombotic medications in endovascular thrombectomy patients were among the notable limitations. As a result, the findings of the trial suggest a need for improvement in thrombolysis to better save brain tissue in acute ischemic stroke.

Insights From Other Studies

Additional studies reinforce the time-dependent nature of effective stroke treatment. An individual participant data meta-analysis from six randomized clinical trials found that intravenous thrombolysis (IVT) plus thrombectomy was significantly associated with a favorable shift in functional outcome at 90 days vs thrombectomy alone if administered within 2 hours 20 minutes of symptom onset. Beyond this timeframe, the benefit associated with IVT lessened significantly.

Conclusion

The findings of the MOST trial underscore the need for ongoing research and improvements in the field of thrombolysis for acute ischemic stroke. While the trial did not yield the expected results, it has provided valuable insights that can guide future research and treatment strategies. Ultimately, the goal is to optimize the total proportion of stroke patients who achieve functional independence 90 days after the stroke, and each trial brings us a step closer to realizing this goal.