Lowering blood pressure in acute stroke: lessons learnt from the SCAST trial

Abstract

The management of high blood pressure (BP) during the acute phase of stroke has remained an enigma for more than 25 years, exemplified by a debate published back in 1985 [1]. While observational studies show that high BP is independently associated with a poor outcome, patho physiology argues that lowering BP will reduce cerebral blood flow (CBF) in the face of dysfunctional autoregulation. Thus, lowering BP might improve or worsen outcome, depending on whether epidemiology or pathophysiology is more important. Such uncertainty in this common complication of stroke (80% of patients are affected) demands large definitive randomized controlled trials, and the first such study has recently been published. The 2029-patient Scandinavian Candesartan Acute Stroke Trial (SCAST) examined whether careful BP lowering with oral candesartan, an angiotensin receptor antagonist (ARA), was safe and beneficial in patients with acute ischemic stroke (85%) or primary intracerebral hemorrhage (PICH; 14%), and raised BP (systolic blood pressure [SBP]: ≥140 mmHg; mean: 171/90 mmHg) [2]. As patients had to be able to swallow, baseline stroke severity was mild (Scandinavian Stroke Scale: 41). The mean time to recruitment was 18 h up to a maximum of 30 h. The results for the coprimary outcomes in SCAST were surprising; in comparison with placebo, treatment with candesartan was associated with a nonsignificant worse functional outcome (assessed using the modified Rankin Scale) at 6 months (adjusted common odds ratio: 1.17; 95% CI: 1.00–1.38; p = 0.048) and no reduction in vascular events (adjusted hazard ratio: 1.09; 95% CI: 0.84–1.41; p = 0.52) [2] (as there were two coprimary outcomes, the trend to a worse functional outcome is nonsignificant, since p > 0.025). So, why was SCAST carried out, and how can these results be explained? Scandinavian Candesartan Acute Stroke Trial was the natural follow-on from an earlier trial, Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) [3], which also assessed candesartan in acute ischemic stroke. Although the primary outcome in ACCESS – function measured as the Barthel Index at 3 months – was neutral (with a negative trend), a 52% reduction in a composite vascular outcome (comprising death, cerebro vascular and cardiovascular events at 12 months) was observed, a finding that captured the imagination of many physicians. The results of ACCESS [3] for vascular events (but not functional outcome) are divergent with those of SCAST however, notably, it was six-times smaller and so its results Expert Rev. Neurother. 11(8), 1091–1094 (2011)