An overview of acute stroke therapy -: Past, present, and future

The effort to develop effective therapies for acute ischemic stroke achieved several important successes during the past decade, but also many disappointing failures. The 2 primary successes were related to thrombolysis. The first was the NINDS rt-PA (National Institute of Neurological Disorders and Stroke Recombinant Tissue-Type Plasminogen Activator) trial reported in 1995, This study demonstrated that initiation of intravenous (IV) rt-PA within 3 hours after the onset of acute ischemic stroke significantly improved outcome at 3 months.(1) This study led to the approval of rt-PA initiated within 3 hours of stroke onset as the only currently available acute stroke therapy. The second major success was the demonstration that intra-arterial prourokinase initiated within 6 hours of stroke onset in patients with angiographically documented proximal middle cerebral artery (MCA) occlusion also improved outcome at 3 months.(2) A third marginally positive acute stroke trial used ancrod, a defibrinogenating agent derived from Malaysian pit vipers.' Ancrod initiated within 3 hours after stroke onset also improved 3-month outcome but to a lesser degree than either rt-PA initiated within 3 hours or prourokinase initiated within 6 hours. These successful acute stroke therapy trials were outweighed by a large number of neuroprotective trial failures. Currently, not one of many purported neuroprotective therapies assessed in pivotal clinical trials has demonstrated unequivocal, statistically significant improvement in clinical outcome.(4) The neuroprotective trials all included patients who presented with a stroke 3 hours after onset, and the therapies used for each patient failed for myriad reasons that will be explored in detail.