Drug-Eluting Versus Bare-Metal Stents in Saphenous Vein Bypass Graft PCI

Glenn N. Levine, MD, FAHA, FACC

Review

Aggarwal V, Stanislawski MA, Maddox TM, et al. Safety and effectiveness of drug-eluting versus bare-metal stents in saphenous vein bypass graft percutaneous coronary intervention. J Am Coll Cardiol 2014;64:1825-1836.

It is generally accepted that drug-eluting stents (DES) decrease the risk of restenosis in native coronary arteries compared with bare metal stents (BMS). However, the overall safety and benefit of DES implantation, including long-term benefits, in saphenous vein bypass grafts (SVGs) remains the subject, at least to some extent, of continued evaluation. This issue is of great clinical importance because by 10 years after bypass surgery, half of SVGs are occluded, and of those still potent, half are diseased.^1,2 A recent report³ by Aggarwal and colleagues adds to our understanding of who is being treated with DES for SVG percutaneous coronary intervention (PCI) and what the short- and long-term outcomes of their use are compared with BMS for SVG-PCI.

Study Details

In this study, Aggarwal and colleagues sought to utilize data from the Veterans Affairs (VA) CART Program to assess patient and lesion characteristics and the acute and long-term outcomes of patients treated with DES or BMS during SVG-PCI. The VA-CART program is a national database of all 63 VA medical centers that perform PCI. The data are linked with VA electronic health records, allowing for linkage to longitudinal outcome data, as well as fee-based data for non-VA care. Data elements in VA-CART are standardized and based on the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) for catheterization-PCI.

This retrospective study used data from all patients undergoing their first procedure of a SVG-PCI from October 1, 2007, through September 30, 2011. Patients who had undergone previous SVG-PCI, who received both DES and BMS, or had missing key data were excluded from analysis. Overall, approximately two-thirds of treated patients received DES. Of that group, 34% received first-generation DES (defined as either paclitaxel-eluting or sirolimus-eluting stents) and 64% received second-generation DES (defined as either everolimus-eluting or zotarolimus-eluting stents). Approximately 56% of patients had non-ST-elevation acute coronary syndromes (NSTE-ACS), 5% had ST-segment elevation myocardial infarction (STEMI), and 26% had stable angina or chest pain (the remainder of the procedures were for other or unclear indications). Outcomes were analyzed using propensity-matched cohorts using Cox proportional hazards regression models.

The use of DES increased each year of the study, from 50% the first year to 69% during the last year. DES tended to be used more commonly for anastomotic lesions; BMS tended to be used more commonly in treating lesions in the “body” of the SVG. DES tended to be used more commonly in SVG to a diagonal branch, whereas BMS tended to be used more commonly in SVG to the right coronary artery. Use of embolic protection devices was similar with DES and BMS (a somewhat disappointing 38%-39%). In general, procedural complication rates were low and comparable between those treated with DES and those treated with BMS. For the overall (nonpropensity-matched) study population, the incidence of procedural complication was 2.3% in DES-treated patients and 2.8% in BMS-treated patients (P = .54). For the propensity-matched cohort, no procedural complication was reported in 93.7% of DES-treated patients and in 93.9% of BMS-treated patients (P = .54). Post procedure thrombolysis in myocardial infarction (TIMI) flow grade 3 was reported in 88.6% of DES-treated patients and in 89.2% of BMS-treated patients.

Over a mean follow-up of 30 months, there was no significant difference in MI rates between those receiving a DES and those receiving a BMS. The adjusted hazard ratio (HR) for any DES versus BMS was .94 (CI, .71-1.24), the adjusted HR for first-generation DES versus BMS was .88 (CI, .62-1.23), the adjusted HR for second-generation DES versus BMS was 1.00 (CI, .72-1.36), and the adjusted HR for second-generation DES versus first-generation DES was 1.13 (CI, .81-1.58).

In the propensity-matched cohort, over a mean follow-up of 33 months, patients receiving a DES were less likely to experience mortality than those receiving a BMS (HR, .72; CI, .57-.89). This finding did not change after further adjusting for lesion location within the graft and target native vessel. There was no statistically significant difference in mortality between those treated with a first- or second- generation DES.

CommentaryMore evidence in favor of the use of DES in patients undergoing SVG-PCI

The study investigators are to be commended on this comprehensive report on SVG-PCI in a large patient population (2472 patients), which utilized excellent statistical analyses. A few findings do, however, merit comment. The low complication rates, particularly the low rates of periprocedural MI (.5%), seem quite low and may reflect self-reporting and incomplete assessment of troponin-measured myocardial necrosis. SVG age is not reported, and it is possible that there may be differences between the 2 groups that could influence event rates. There is a clear disconnect between the similar MI rates, yet notable difference in observed mortality rates. Although the authors used propensity-matched analysis, this at least suggests the possibility that some factors could not be accounted for. Perhaps DES were preferentially placed in patients judged to be healthier and more apt to tolerate prolonged dual antiplatelet therapy (DAPT), while BMS were preferentially placed in patients judged to be more frail and less likely to tolerate prolonged DAPT? Somewhat along these lines, no data are presented on duration of DAPT. Although it is unlikely that additional months or even several years of DAPT would significantly impact overall mortality to the degree seen in this study (if at all), this nevertheless is an additional consideration in interpreting the results of this study.

Numerous prior cohort studies, several randomized trials, and meta-analyses have compared outcomes in patients undergoing SVG-PCI treated with either DES or BMS.⁴ In the ISAR-CABG study, 610 patients undergoing SVG-PCI were randomized to treatment with either DES or BMS. The composite primary end point of death, MI, and target lesion revascularization (TLR) at 1 year occurred in 15% of DES-treated patients and 22% of BMS-treated patients (HR, .64; CI, .44-.94; P = .02). TLR was halved with DES treatment (7% vs 13%; HR, .49; CI, .28-.86; P = .01), and there were no significant differences in definite or probable stent thrombosis, MI, or all-cause mortality.⁵ In a meta-analysis of studies comparing DES with BMS for SVG-PCI, Wiisanen and colleagues reported that patients treated with DES had a lower risk of TLR (OR, .57; CI, .40-.82), major adverse cardiac events (OR, .61; CI, .42-.79), and mortality (OR, .75; CI, .59-.96).⁴

The 2011 American College of Cardiology Foundation / American Heart Association / Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) Guideline for Percutaneous Coronary Intervention does not make a specific formal recommendation regarding the use of DES in SVG-PCI, but does list SVG-PCI as a clinical situation in which DES are generally preferred over BMS.⁶ The 2014 European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularization similarly do not give a specific formal recommendation regarding choice of stent in SVG-PCI, but they do note that the increased efficacy and safety of new-generation DES have enabled their unrestricted use in patients with coronary artery disease and an indication for PCI, including patients with SVG lesions. Therefore, they should be considered by default in all clinical conditions and lesion subsets.⁷

Thus, the propensity of data and expert opinion favors the use of DES in patients undergoing PCI. This latest analysis by Aggarwal and colleagues does not, at the very least, contradict this confluence of data and opinion; in fact, it seems to further support it. Additional data will likely be available at the end of 2016 when results of the VA Cooperative Study Drug-Eluting Stents vs Bare Metal Stents in Saphenous Vein graft Angioplasty (DIVA) study⁸ become available.

References

1. Taggart DP, Banning AP. Stents and failing vein grafts: are we any wiser after ISAR? Lancet. 2011;378(9796):1054-1055.

2. FitzGibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am Coll Cardiol. 1996;28(3):616-626.

3. Aggarwal V, Stanislawski MA, Maddox TM, et al. Safety and effectiveness of drug-eluting versus bare-metal stents in saphenous vein bypass graft percutaneous coronary intervention. J Am Coll Cardiol. 2014;64:1825-1836.

4. Wiisanen ME, Abdel-Latif A, Mukherjee D, Ziada KM. Drug-eluting stents versus bare-metal stents in saphenous vein graft interventions: a systematic review and meta-analysis. JACC Cardiovasc Interv. 2010;3(12):1262-1273.

5. Mehilli J, Pache J, Abdel-Wahab M, et al. Drug-eluting versus bare-metal stents in saphenous vein graft lesions (ISAR-CABG): a randomised controlled superiority trial. Lancet. 2011;17;378(9796):1071-1078.

6. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-e122.

7. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541-2619.

8. Drug-Eluting Stents vs. Bare Metal Stents In Saphenous Vein Graft Angioplasty (DIVA) study. Clinical trials website. http://clinicaltrials.gov/show/NCT01121224

About the Author

Glenn N. Levine, MD, FAHA, FACC, is professor of medicine at Baylor College of Medicine, and director of the Cardiac Care Unit at Michael E. DeBakey Medical Center in Houston, Texas. He received his MD from Columbia University College of Physicians and Surgeons in New York City and completed postdoctoral training in advanced cardiovascular imaging at Baylor College of Medicine/Texas Heart Institute. Dr Levine’s internship, residency, and fellowships in interventional cardiology and cardiology were at Boston University Medical Center. He has coauthored numerous published clinical trials, guidelines, and textbook chapters.