Investigational drugs for vasospasm after subarachnoid hemorrhage

ABSTRACT

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) represents 3% of all strokes in the US. When the patient survives it can lead to permanent incapacity especially if the patient develops vasospasm. The vasospasm is a multifactorial disorder and can lead to delayed cerebral ischemia (DCI). Most of the drugs tested to treat vasospasm failed to improve outcome and the only exception is nimodipine.

Areas covered: In this review, the authors describe the multifactorial process of vasospasm leading DCI after aSAH, discussing the treatments available based on the past and latest researches.

Expert opinion: Nimodipine is the only FDA-approved medication with neuroprotective effect and able to improve outcomes after aSAH. Understanding nimodipine trials is mandatory to understand and criticize all the drug trials published until now. The mechanism to vasospasm is multifactorial and not completely understood and all the other attempts to find a better medication could not prove superior results. Newton and PEGylated Carboxyhemoglobin Bovine can be potentially effective to prevent vasospasm but we still need more data and large studies. Future research should investigate newer drugs, as well as the combination of multiple drugs therapy and the association with blood evacuation techniques.

KEYWORDS:

• Delayed cerebral ischemia
• nimodipine
• subarachnoid hemorrhage
• vasospasm

Article highlights

• ”Vasospasm” is a multifactorial neurovascular pathology after aneurysmal subarachnoid hemorrhage (aSAH) that remains poorly understood and leads to delayed cerebral ischemia (DCI) and cerebral infarction.

• Nimodipine is FDA- approved andproven to improveneurological outcomes in randomized, placebo-controlled trials although it’s exact mechanism of neuroprotection remains unknown.

• Clazonseltan, simvastatin and magnesium failed to demonstrate benefit in aSAH vasospasm prevention.

• Milrinone and intraventricular nicardipine require larger or randomized trials to demonstrate benefit.

• Prolonged-release intraventricular nimodipine (NEWTON-2 trial) and PEGylated Carboxyhemoglobin Bovine may provide therapies for DCI prevention

• Multimodal trials or SAH ‘bundles’ adding more than one drug and associating others techniques, such as lumbar drainage, shouldbe the considered in aSAH for vasospasm and DCI prevention.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. One peer reviewer previously received research funding for a project studying SANGUINATE^TM, a product mentioned in this paper.

Additional information

Funding

This paper isnot funded.