Implications for an early intensive blood pressure lowering strategy in patients with acute ischaemic stroke

Abstract

Background and Objectives: The management of elevated blood pressure (BP) in patients with acute ischaemic stroke (AIS) remains controversial. While large randomised controlled trials, such as the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), have quantified the effects of early intensive BP lowering on functional recovery, further investigations are required to reliably define the balance of risks and benefits in different patient groups. In particular, the INTEnsive ambulance-delivered BP Reduction in hyper-Acute stroke Trial (INTERACT4) aims to define the risks and benefits of intensive BP lowering treatment in the first 2 hours of stroke onset. This thesis explores the effects of early intensive BP lowering to a systolic target of 130-140 mmHg in different time points (<2 hours in the ambulance or <6 hours in hospital) on functional recovery, and injury to the brain and kidney, in AIS patients. It also examines regional differences in BP management to facilitate the uptake of evidence-based recommendations. Methods: These were secondary analysis of the ENCHANTED and INTERACT4 trials, with a focus on functional recovery on the modified Rankin scale, infarct volume assessed on brain imaging, and short-term changes in renal function according to estimations of serum creatinine. Regional differences in antihypertensive treatment were examined in the international multicentre ENCHANTED trial. Results: The findings indicate that intensive BP lowering to a systolic target of 130-140 mmHg is harmful in AIS patients, with worsening of functional recovery and increased mortality when initiated within 2 hours after the onset. However, initiating this treatment within 6 hours in thrombolysed AIS patients is safe according to infarct volume and renal function. There are considerable regional differences in the use of BP lowering treatment in AIS patients. Conclusions: My research has shown that a moderate intensity of BP lowering before reperfusion therapy in AIS patients is harmful and should be avoided. However, this BP lowering treatment after reperfusion therapy does not appear harmful, but more work is required to define whether it provides beneficial effects on functional recovery. Regional differences in the use of BP lowering treatment in AIS translated into differences in BP parameters and needs to be considered in the design and interpretation of trial results. Further research is needed to optimise BP management in AIS