BARI 2D - Where has it taken us to and what the future has in store for us

Abstract

Background: Optimal therapy for diabetics with stable coronary artery disease and mild symptoms has not yet been established. The BARI 2D study is the successor to the BARI study where diabetics (especially those on insulin) had a worse long-term outcome after revascularization compared with other populations. The multicenter clinical BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Study took place from 2001-2008. It compared early revascularization (ER - either PCI or CABG) with medical therapy (MT), together with intensive pharmacotherapy and lifestyle intervention in both groups. At the same time, two diabetes drug treatment strategies ("insulin sensitizers" - ISs and "insulin providers"- IPs) were compared. The primary endpoint was 5-year all-cause mortality. Methods: A total of 2 368 patients with type-2 diabetes with stable coronary artery disease suitable for revascularization (with the choice of actual intervention dependent on the cardiologist) were randomized to either ER or MT. Simultaneously, independent randomization to either IS or IP diabetes treatment was performed. The average follow-up period was 5.3 years. Results: Overall 5-year mortality was 11.7% (n = 137) in the ER group vs. 12.2% (n = 145) in the MT group (p = 0.97, n.s.) and 11.8% (n = 139) in the IS group vs. 12.1 % (n = 143) in the IP group, (p = 0.89, n.s.). The secondary composite endpoint (death + nonfatal myocardial infarction + stroke) findings were also not statistically significant: ER 22.8% (n = 268) vs. MT 24.1 % (n = 287), p= 0.70, and IS 22.3% (n = 264) vs. IP 24.6% (n = 291), p= 0.13; subgroup analysis showed that the rate of major cardiovascular (CV) events in those scheduled for CABG was significantly lower in the ER group than in the MT group (22.4% vs. 30.5%, p= 0.01). Conclusion: None of the treatment strategies showed a clear benefit in terms of reducing mortality or major cardiovascular events - there was no significant difference between the initial revascularization group versus the medical therapy group, nor between the "insulin sensitization" versus the "insulin provision" groups. The only significant difference - fewer major CV events in the early revascularized patients scheduled for CABG - is probably related to the less severe coronary artery disease in these patients.