The ARAMIS trial (allopurinol in patients with refractory angina to improve ischemic symptoms)

Abstract

One of the most common clinical presentations associated with coronary artery disease (CAD) is stable angina, which can be translated clinically by chest discomfort (or equivalent) evoked by different levels of physical activity depending on the extent of the disease. Despite the undeniable advances in medical treatment and revascularization procedures (percutaneous and surgical), many patients present debilitating symptoms that are not responsive to conventional treatment due to disease progression (chronic arterial occlusion, diffuse involvement of the distal arterial bed, or post-angioplasty restenosis), making it impossible to re-attempt myocardial revascularization, a condition known as refractory angina. The mark of this condition is the great impairment in quality of life. Usually, those affected are unable to perform any physical activity without the appearance of angina. For these patients, the main goal of treatment is to improve quality of life, increase tolerance to exercise and decrease the need for hospitalization and diagnostic or therapeutic procedures. Recently, the Brazilian Society of Cardiology in its latest Stable Angina Guidelines incorporated allopurinol as the 4th line of treatment for symptomatic control in patients not responding to conventional agents (beta-blockers, calcium antagonists and/or long-acting nitrates) despite the scant data in the literature on its real antianginous efficacy.In this study, we will test the hypothesis that high doses of allopurinol are safe and well tolerated, and may decrease the frequency and intensity of angina attacks, as well as increase tolerance to effort and quality of life in patients with difficult-to-control angina, nonresponsive to usual therapy. It is a randomized (1: 1), double-blind, placebo-controlled study in which 40 patients with refractory angina in optimal medical therapy will be included. The primary endpoint will be the reduction of angina attacks and the use of short-acting nitrates, improvement of functional class and increase of effort tolerance evaluated through the Diary of Angina and Quality of Life Questionnaires, in addition to the cardiopulmonary test and echocardiography with colour Doppler at rest and during physical exertion. Vascular reactivity will be assessed through the reactive hyperemia test in the upper limb. The safety of allopurinol will be determined by clinical and laboratory evaluation. (AU)