Rapid blood pressure lowering treatment in acute intracerebral haemorrhage

Abstract

Acute spontaneous intracerebral haemorrhage (ICH) occurs when a diseased blood vessel ruptures within the brain, allowing blood to track inside the brain to damage tissues and raise intracranial pressure from the mass effect of the resulting haematoma. ICH is less common than acute ischaemic stroke due to occlusion of an intracerebral vessel, accounting for between 10% and 35% of strokes according to the at-risk population. Temporal trends in the incidence of ICH appear stable and its prevalence is increasing in aging populations. The high burden of premature death and disability associated with ICH is well established and treatment options, either medical or surgical, are limited. The most common cause of ICH is elevated blood pressure (BP) and the hypertensive response at presentation also predicts a poor outcome. The INTEnsive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (pilot [INTERACT1] and (main [INTERACT2] phases) were undertaken to determine whether early intensive lowering of BP would improve clinical outcomes, and were conducted over a 10-year period from 2006 to 2012. They included patients with spontaneous ICH within 6 hours of onset and associated high systolic BP (SBP) who were randomised to lower level (target SBP <140 mmHg within 1 hour) or contemporaneous guideline-recommended higher level (target SBP <180 mmHg) of routinely available BP lowering treatment. INTERACT2 was the largest randomised evaluation of a treatment in ICH, using a pragmatic design to establish the effectiveness of a potentially widely applicable treatment. The treatment effect on the primary outcome, according to the conventional binary analysis of death or major disability (i.e. scores of 3 to 6 on the modified Rankin scale [mRS]) at 90 days was not significant (P=0.06) at the conventional P <0.05 level. However, the key secondary outcome using an ordinal analysis across all grades on the mRS indicated significantly improved functional outcomes in patients who received intensive BP lowering. In this thesis, I undertook further analyses of the INTERACT datasets to provide further evidence to support the beneficial effects of early intensive BP lowering treatment in ICH. Specific sections of the thesis present different aspects of BP lowering treatment and ancillary management of patients.