Combining Statins with Tissue Plasminogen Activator Treatment After Experimental and Human Stroke: A Safety Study on Hemorrhagic Transformation

AimsStatins may afford neuroprotection against ischemic injury, but it remains controversial whether combined treatment with tissue plasminogen activator (tPA) after stroke increases the risk of hemorrhagic transformation (HT), the major tPA-related complication. We evaluated the safety of combining statin with tPA administration during the acute phase of both experimental and human stroke. MethodsThe occurrence and severity of HT, infarct volume, and neurological outcome were evaluated in spontaneous hypertensive rats (SHR) subjected to embolic middle cerebral arterial occlusion (MCAO), which received vehicle or simvastatin (20mg/kg), 15min after ischemia and tPA (9mg/kg) 3h after ischemia. Additionally, HT rate was evaluated in stroke patients who were treated with tPA (0.9mg/kg) within 3h after symptom onset, considering whether or not were under statins treatment when the stroke occurred. ResultsIn the experimental study, no differences in HT rates and severity were found between treatment groups, neither regarding mortality, neurological deficit, infarct volume, or metalloproteinases (MMPs) brain content. In the clinical study, HT rates and hemorrhage type were similar in stroke patients who were or not under statins treatment. ConclusionThis study consistently confirms that the use of statins does not increase HT rates and severity when is combined with tPA administration.