Thrombolysis for PE: less is more?

Despite the significant advances in diagnostic imaging, risk stratification and anticoagulants over the past two decades in the field of PE, very little progress has been made in clarifying the role of thrombolysis in the treatment of submassive or intermediate-risk PE. Perhaps the simplest illustration of our uncertainty is that guideline committees struggle to come up with consistent recommendations. While the National Institute for Health and Care Excellence (NICE) Clinical Guideline 144 makes it clear that thrombolysis should not be administered to patients outside the context of haemodynamic instability,1 the European Society of Cardiology (ESC) guidelines leave open the possibility that we ‘consider’ reperfusion therapy in some patients with intermediate-high risk PE.2 While NICE guidance does not perhaps reflect the complexity of different presentations of PE, the ESC guidelines leave us with a great deal of uncertainty when making major clinical decisions. Large randomised controlled trials have not been able to provide a clear answer; rather they leave us with further hypothesis-generating conclusions. The Pulmonary Embolism Thrombolysis (PEITHO) trial randomised over 1000 patients with ESC-defined intermediate-high risk PE (haemodynamically stable, right ventricular dysfunction on imaging and positive troponin) to placebo or tenecteplase.3 One would imagine that with a positive primary endpoint, this would have provided clear direction; however, it did not. This is because the primary endpoint was a composite of mortality and haemodynamic collapse at 7 days and, while relevant, this does not take account of the significant morbidity burden associated with bleeding in the tenecteplase arm. Restricting the outcome to mortality alone at 30 …