Diabetes and Revascularization Techniques: Some Good News!
Abstract & commentary
By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.
Source: Daemen J, et al. Multivessel coronary revascularization in patients with and without diabetes mellitus: 3-year follow-up of the ARTS-II (Arterial Revascularization Therapies Study-II) trial. J Am Coll Cardiol. 2008;52:1957-1967.
Diabetics are known to have higher rates of restenosis after revascularization than non-diabetic subjects. Controversy about whether bare-metal stents (BMS) or coated stents (drug eluting with sirolimus) are better in diabetics, and the superior outcomes of coronary artery bypass graft surgery (CABG) in diabetics when compared to BMS remains to be seen. The older ARTS-I trial and other trials have demonstrated that CABG is superior to BMS in multivessel disease, particularly in diabetics. ARTS-II represents a more recent trial to assess percutaneous revascularization (PCI) with sirolimus-eluting stents (SES), comparing outcomes with CABG and PCI with BMS in ARTS-I; safety and efficacy were the primary endpoints. Non-diabetics and diabetics in ARTS-II were followed for three years, using the results of CABG and BMS in ARTS-I as a historical comparison.
ARTS-I was a multi-center European study that enrolled 1,200 patients from April 1997 to June 1998 in two groups: BMS and PCI, and CABG. In ARTS-II, 607 patients were enrolled between February 2003 and November 2003. The primary endpoints in ARTS-II were safety and efficacy of SES in comparison to CABG and BMS in ARTS-I subjects over three years. The primary efficacy endpoint was a composite of death, MI, CVA, and repeat revascularization. Enrolled patients had to have at least two severe lesions in different epicardial vessels. CK-MB measurements were used, but troponin data was not available. The ARTS-II cohort had more three-vessel disease patients, type C lesions, and more stents per patient than ARTS-I patients.
Results: The primary endpoint was significantly lower in the ARTS-II cohort (OR 0.41, CI 0.26 to 6.4) compared to ARTS-I PCI, and was similar to ARTS-I CABG. Also, death, MI, and stroke were significantly lower in ARTS-II vs ARTS-I PCI (OR 0.55, CI 0.34-0.91) and ARTS-I CABG (0.56, CI 0.35-0.92). ARTS-II diabetics had higher rates of hypertension and elevated cholesterol compared to ARTS-I subjects. ARTS-II patients had more high-risk individuals, with more three-vessel disease, type C lesions, and more stents utilized. The primary endpoint in ARTS-II was similar to ARTS-I PCI and CABG. However, death, MI, and stroke rates were lower in ARTS-II patients as compared to ARTS-I PCI (OR 0.72), and similar to, ARTS-I CABG.
Insulin-using diabetics had worse outcomes (but low numbers of patients after adjustment). Diabetes was the strongest predictor of major events in ARTS-II. The incidence of major events in diabetics was significantly higher than in non-diabetic patients, driven mostly by repeat revascularization. Surprisingly, stent thrombosis at three years was similar in ARTS-II diabetic and non-diabetic patients (6.9% vs 6.3%), but 23% of ARTS-II diabetics with a major event had stent thrombosis. In ARTS-II, at three years, diabetics had an 81% increased risk for repeat revascularization compared to non-diabetics, but lower than that observed in the ARTS-I CABG group. There was a 44% lower need for repeat revascularization in ARTS-II diabetics. Overall, there was a 70% higher risk for major events in diabetics compared to non-diabetics in ARTS-II. Stent thrombosis was 3.8%, equal in both groups of patients. Daemen et al concluded that PCI with SES or CABG is safer and more efficacious than PCI with BMS in diabetics, as well as non-diabetics.
The finding that coated stents in diabetic patients with multivessel disease may level the playing field vs CABG, reflects an important improvement in the revascularization approach to diabetics with severe CAD. Considerable older data have demonstrated poorer clinical outcomes in CABG-treated, multivessel-disease diabetic patients. However, not all reports have found differences in mortality with PCI or CABG in diabetics. ARTS-II, a comparative report on PCI in CAD patients with and without diabetes, does appear to support improved clinical outcome in diabetics with drug-eluting stents. The data in ARTS-I and in ARTS-II reflect older studies (ie. 10 years ago in ARTS-I (no coated stents) and 5-6 years ago in ARTS-II) using PCI patients receiving SES. Troponin levels were not obtained and/or reported, making the identification of non-ST-elevation MI in subjects difficult. Multiple factors in diabetes (small vessel size, increased platelet activity, aggressive atherosclerosis, higher restenosis rates, and decreased survival) vs non-diabetics are all well documented. This report is not surprising, confirming a true advantage for SES in diabetics. This seems reasonable, although controversy over surgical revascularization and contemporary PCI remains in diabetes.
Daemen et al emphasize that many current trials are underway to further delineate the relationships of PCI and CABG. Studies to be watched for as to whether or not PCI with SES or paclitaxil stents is truly equivalent to CABG include: FREEDOM, CARDIA, SYNTAX. At present, PCI using SES, or perhaps paclitaxil, could be a genuine alternative to CABG. The results of large-scale, randomized trials are eagerly awaited to validate these findings.