Succinobucol should not be used for treating patients with acute coronary syndromes or for treating or preventing diabetes until a number of both beneficial and harmful outcomes connected with its use have been further investigated. These are the conclusions of authors of an Article in this week's Diabetes Special Issue of The Lancet.
Oxidative stress and inflammation are involved in the development of atherosclerosis. The antioxidant drug probucol has been shown to reduce atherosclerois. Succinobucol is closely related to probucol with greater antioxidant strength and anti-inflammatory properties. Dr Jean-Claude Tardif, Montreal Heart Institute, University of Montreal, Canada, and colleagues did a randomised controlled trial to test the effects of succinobucol on cardiovascular outcomes in patients with recent acute coronary syndromes already managed with conventional treatments.
A total of 6144 patients were randomly assigned to receive either succinobucol (3078) or placebo (3066). The primary endpoint was the composite of time to first occurrence of cardiovascular death, resuscitated cardiac arrest, heart attack, stroke, unstable angina, or coronary revascularisation. While the researchers found no difference between succinobucol and placebo for the primary endpoint, the composite secondary endpoint of cardiovascular death, cardiac arrest, heart attack, or stroke occurred in 19% fewer patients in the succinobucol group than in the placebo group. The tertiary endpoint of new-onset diabetes developed in fewer patients without diabetes at baseline in the succinobucol group (30) than in the placebo group (82) -- a relative difference of 63%. New-onset atrial fibrillation occurred almost twice as frequently in the succinobucol group compared with placebo, and more patients in the succinobucol group reported bleeding episodes or anaemia as serious adverse events. Relative to treatment with placebo, succinobucol increased LDL (bad) cholesterol and systolic blood pressure, and decreased HDL (good) cholesterol. Interestingly, glycated haemoglobin (a standard measure of long-term diabetes control) was significantly improved by succinobucol.
The authors conclude: "Although succinobucol had no effect on the primary endpoint, changes in the rates of other clinical outcomes -- both beneficial and harmful -- will need to be further assessed before succinobucol is used in patients with atherosclerosis or as an antidiabetic agent."
In an accompanying Comment, Dr Stephen J Duffy and Professor Anthony M Dart, Alfred Hospital and Baker Heart Research Institute, Melbourne, VIC, Australia say: "Although there is compelling evidence of increased oxidative stress and inflammation in atherosclerosis, clinical studies of treatments targeting these pathophysiological events have been disappointing. The best available treatments for these processes continue to be a diet rich in fresh fruit and vegetables, blockade of the renin-angiotensin system, lipid-lowering with statins, and possibly aspirin."
For Dr Jean-Claude Tardif, Montreal Heart Institute, Montreal, Canada please contact Doris Prince, Head of Communications T) +1 514 376-3330, ext. 3074 E) Jean-Claude.Tardif@icm-mhi.org /doris.prince@icm-mhi.org
Dr Stephen J Duffy, Alfred Hospital and Baker Heart Research Institute, Melbourne, VIC, Australia T) +61 3 9076 2732 E) s.duffy@alfred.org.au
http://multimedia.thelancet.com/pdf/press/succinobucol.pdf
Journal
The Lancet