Hypotension and ischaemic stroke associated with aliskiren in the ALTITUDE trial: sensitisation of the Bezold-Jarisch reflex?

Hypotension and syncopal attacks have been reported in association with drugs which block the renin-angiotensin-aldosterone system (RAAS). It has been proposed that the underlying mechanism is due to sensitisation of the Bezold-Jarisch reflex leading to withdrawal of sympathetic tone, profound and prolonged bradycardia, and hypotension. Sensitisation of this reflex occurs in the presence of blockade of the RAAS. In the ALTITUDE trial the use of the direct renin inhibitor, aliskiren, was associated with hypotensive episodes and an excess of ischaemic stroke. It is hypothesised that this is best explained by activation of the Bezold-Jarisch reflex, which may be particularly important in circumstances where there is dual blockade of the RAAS.