The effect of HMG-CoA reductase inhibitors on thrombolysis-induced haemorrhagic transformation

Abstract

Thrombolysis-induced haemorrhagic transformation is the most challenging preventable complication in thrombolytic therapy. This condition is often associated with poor functional outcome and long-term disease burden. Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are controversially suggested to either increase or decrease the odds of better primary outcomes compared to treatment without statins after thrombolysis in patients or animals; statins are thought to act by influencing lipid levels, the inflammatory response, blood brain barrier permeability and cell apoptosis. Statins are the cornerstone of secondary prevention of cardiovascular and cerebrovascular diseases. However, the role of statins in acute phase stroke, and the necessity of their use, remains unclear. Currently, whether statins can increase the risk of haemorrhagic transformation is of great concern for patients treated with tissue plasminogen activator (t-PA). Herein, we thoroughly summarize the recent advances that address whether the administration of statins in ischaemic stroke increases haemorrhagic transformation in patients or animals who received thrombolysis at an early stage and the related mechanisms. This review will provide more clinical and preclinical evidence to address questions regarding the exercise of caution in the use of high dose statins in patients who received thrombolysis and if low dose statins may be beneficial in decreasing thrombolysis-induced haemorrhagic transformation.

Keywords: Acute ischaemic stroke; Haemorrhagic transformation; Statins; Thrombolysis; Tissue plasminogen activator (t-PA).