Secondary results of ARISE trial are promising, hypothesis generating
J.C. Tardif, Canada
A study targeting inflammation acute coronary syndromes (ACS) with a novel treatment failed to meet its primary endpoint, but investigators believe the positive results for the secondary endpoints show promise for improving outcomes and provide valuable information for designing more trials with this agent. Dr. Jean-Claude Tardif, Montreal, Canada, presented the results of the ARISE (Aggressive Reduction of Inflammation Stops Events) at the 56th Scientific Sessions of the American College of Cardiology, held from March 24-27, 2007.
Oxidative stress and inflammation are involved in the pathophysiology of atherosclerosis. Succinobucol, the monosuccinic acid ester of probucol, is a lipophilic antioxidant with anti-inflammatory properties that has shown favorable results in preclinical and clinical studies. The ARISE trial assessed the potential benefit of adding this new agent in addition to standard of care in patients surviving an ACS, and included patients from Canada, South Africa, the UK, and the US.
The 6,144 patients enrolled in the double-blind, placebo-controlled international trial were high-risk cardiovascular patients because of age (mean age 65), prior myocardial infarction (MI) (72%) or revascularization (83%), diabetes (37%), hypertension (72%), or multiple risk factors. All patients were receiving optimal medical therapy. Patients were randomized to succinobucol 300 mg daily or placebo and followed for 2 years. The primary endpoint was a composite of major adverse cardiovascular events (CV death, resuscitated cardiac arrest, MI, stroke, unstable angina, or coronary revascularization.
A similar rate of primary endpoint events was found (17.2% succinobucol vs 17.3% placebo, respectively, p=0.985).
A 19% reduction in the secondary “hard” atherosclerotic composite of CV death, cardiac arrest, MU, or stroke (p=0.028).
A tendency for more heart failure hospitalizations with succinobucol.
A significant 64% reduction in new-onset diabetes with succinobucol (p<0.0001).
Improved glycemic control with succinbucol (reduction of HbA1c by 0.5% at 12 months, P<0.0001) in diabetic patients.
A significant increase in LDL and significant decrease of HDL.
“Although the primary endpoint was not reduced, succinobucol may lead to meaningful reductions in CV death, MI and stroke, as well as new-onset diabetes. These promising findings with this novel therapy require confirmation, but we are pleased with the meaningful improvement of patient outcomes observed with succinobucol in the ARISE trial, which should help to address the burden of cardiovascular risk that exists despite our effective contemporary treatments,” concluded Jean-Claude Tardif.
