Intraparenchymal haemorrhages as a primary outcome measure – Authors' reply

Abstract

We appreciate the interest of Mayank Goyal and colleagues regarding the BP-TARGET trial.1Mazighi M Richard S Lapergue B et al.Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial.Lancet Neurol. 2021; 20: 265-274Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar Their main concern relates to the primary outcome, defined as all intraparenchymal haemorrhages. BP-TARGET was designed in 2015 as a proof-of-concept trial. At that time, with the advent of endovascular therapy, reperfusion rates dramatically increased, and numerous questions remained unanswered regarding medical management after successful endovascular therapy to prevent possible reperfusion injuries. We agree with Goyal and colleagues that type 1 and type 2 parenchymal haemorrhages are more commonly associated with worse outcomes; however, several studies have underlined a deleterious effect of haemorrhagic infarction type 1 and type 2.2Hao Y Liu W Wang H et al.Prognosis of asymptomatic intracranial hemorrhage after endovascular treatment.J Neurointerv Surg. 2019; 11: 123-126Crossref PubMed Scopus (13) Google Scholar, 3Maïer B Desilles JP Mazighi M Intracranial hemorrhage after reperfusion therapies in acute ischemic stroke patients.Front Neurol. 2020; 11599908Crossref PubMed Scopus (8) Google Scholar The modified Rankin Scale score is a simple and validated endpoint, but it remains an inaccurate and imprecise endpoint to fully appreciate neurological outcomes (eg, gait or cognitive impairment). Haemorrhagic infarction type 1 or type 2 could have a deleterious effect on the overall neurological outcome; however, this is not captured by the modified Rankin Scale. For this reason, we believe that the inclusion of all intraparenchymal haemorrhages can give new insights into the neurological management of patients who have had endovascular therapy. Beyond the association of haemorrhagic infarction type 1 and type 2 after endovascular therapy withoutcome, the latter haemorrhagic lesions might substantially change medical management (ie, there is a wide range of intraparenchymal haemorrhage types, possibly limiting the initiation of antithrombotic treatments after endovascular therapy). With the perspective of new antithrombotic strategies to be tested to improve reperfusion, the question as to whether a blood pressure strategy could have an effect on all intraparenchymal haemorrhages after endovascular therapy becomes highly relevant. Beyond this debate regarding the primary endpoint (ie, considering or not all intraparenchymal haemorrhages), we believe that the BP-TARGET trial has highlighted important issues in the blood pressure field, especially for future randomised trials. For instance, which modality should be used to monitor blood pressure in the acute phase (ie, invasive or not), and which blood pressure threshold should be targeted (lower or individualised)? More importantly, is blood pressure after endovascular therapy a prognostic marker rather than a therapeutic target? As future randomised controlled trials will consider the modified Rankin Scale as a primary outcome, we believe that the BP-TARGET trial can provide complementary and additional insights to answer these important questions. MM declares consulting activities for Boehringer Ingelheim, Amgen, Air Liquide, and Acticor Biotech. All other authors declare no competing interests. Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trialAn intensive systolic blood pressure target of 100–129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24–36 h as compared with a standard care systolic blood pressure target of 130–185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion. Full-Text PDF Intraparenchymal haemorrhages as a primary outcome measureWe read with interest the Article by Mikael Mazighi and colleagues,1 who tested whether an intensive blood pressure lowering regimen (target of 100–129 mm Hg systolic) after endovascular therapy resulted in lower rates of radiographic intraparenchymal haemorrhage at 24–36 h compared with the standard of care (130–185 mm Hg systolic) within the BP-TARGET trial. Mazighi and colleagues found no significant differences between the two groups in the primary outcome measure of intraparenchymal haemorrhage. Full-Text PDF