Aneurysmal Subarachnoid Hemorrhage

As noted earlier, the L-type calcium channel blockers nimodipine and nicardipine are available in most countries for the neuroprotective treatment of aneurysmal SAH. The approval of nimodipine specifically was achieved in the early 1990s on the basis of weakly positive data regarding an improvement in survival in SAH patients. The rationale for its use is the expectation that it will inhibit delayed cerebral vasospasm. However, it is more likely that the compound improves microvascular perfusion and/or exerts a direct protective effect on the ischemic brain parenchyma. Nimodipine's usage is accompanied by a great deal of clinical caution due to the legitimate concern about the risk of systemic vasodilatation and hypotension, which can compromise rather than improve cerebral blood flow. Nevertheless, the prior approval of nimodipine for aneurysmal SAH resulted in the subsequent tirilazad SAH clinical development being carried out on top of concomitant nimodipine usage. As noted above, in comparison to nimodipine alone, nimodipine plus tirilazad significantly improved neurological recovery and survival in male patients with aneurysmal SAH.23 Consequently, in the mid-1990s tirilazad was approved for use in males with SAH in Canada, several European countries, Australia, and New Zealand. It has not been approved in the USA, and Pfizer, the current sponsor, is unlikely to rekindle its development for SAH or other neuroprotective indications. Thus, nimodipine and the orally active analog nicardipine are the only agents currently approved for use in SAH in the USA and many other countries.

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