Efficacy of Ranolazine in Patients With Chronic Total Occlusions of Coronary Arteries
Status:
Withdrawn
Trial end date:
2017-03-01
Target enrollment:
Participant gender:
Summary
Anti-anginal drugs relieve ischemia and symptoms by reducing myocardial oxygen demand by
reducing heart rate and or contractility (beta-blockers, phenylalkylamine and
benzothiazepineate classes of calcium antagonists) or vasodilatation of the venous system
(fall in pre-load) and coronary vessels.
Late sodium channels remain open for longer in the presence of myocardial ischaemia.
Ranolazine, a novel anti-anginal agent, acts by inhibiting the inward late inward sodium
current (INaL), reducing intracellular sodium accumulation and consequently intracellular
calcium overload via the sodium/calcium exchanger. It is currently thought that this
reduction in intracellular calcium reduces diastolic myocardial stiffness and therefore
compression of the small coronary vessels. There is considerable animal data to support this
theory.
There are good theoretical reasons to postulate that patients with chronically occluded
vessels may derive less benefit from conventional anti-anginal agents, particularly
vasodilators. The ischemic myocardium, subtended by the occluded vessel, will already be
subject to significant concentrations of paracrine vasodilators such as adenosine.
Ranolazine, therefore, may on the basis of its mechanism of action, provide greater relief of
ischemia in such patients than conventional anti-anginal agents.