Clinical Drug Experience Knowledgebase

Lowering blood pressure reduces the risk of first ever and recurrent stroke. There is extensive evidence that blood pressure should be lowered following acute stroke, even from so called normal levels. However, it is not clear how soon after acute stroke that blood pressure should be lowered. Observational studies have demonstrated increased mortality with both high and low blood pressure. The optimal management of blood pressure in the immediate post-stroke period remains controversial.

Although uncertainty exists with regard to lowering blood pressure in the acute stages of stroke, two large randomised controlled trials have demonstrated unequivocally that intense management of blood pressure started >4 weeks from the onset of stroke significantly reduces the risk of recurrent stroke. Both of these trials have used an Angiotensin Converting Enzyme Inhibitor (ACE-I) based regime. It has been proposed that these benefits may be due to a direct result of the ACE-I rather than blood pressure lowering per se. Similar vasculoprotective effects have been seen in ARBs, but evidence of their safety and efficacy in acute stroke is limited to those patients with the highest blood pressures (>200/110). The trial (ACCESS) was terminated prematurely due to a positive imbalance in favour of intervention with the ARB Candesartan. If such interventions are to convey potential benefit they need to be started as soon as possible following the acute event in order that the ischaemic cascade which leads to neuronal death may be modified. Further research is first required in order to demonstrate their safety and efficacy when used in this way.

ACCOST is a two phase randomised controlled trial designed to address this important research question. Phase I is a four week double blind placebo controlled phase where patients receive either Candesartan 4 mg daily or matched placebo, with no blood pressure treatment target. A treatment titration step occurs after two weeks where, subject to titration criteria, subjects will receive either Candesartan 8 mg daily or matched placebo. After the first four weeks, the subjects are unblinded and enter Phase II of the trial. Phase II is an eight week open label comparison of Candesartan and 'usual care' with an ACE-I based treatment regime. Blood pressure is now treated to reach the British Hypertension Society target blood pressure of <140/85, with or without additional therapy.

Blinded outcome measures will include neurological recovery based on the National Institutes of Health Stroke Scale, as well as functional recovery. Incidence of first dose hypotension and changes in renal function will also be collected.