Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial

Abstract

Background: Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions.

Methods: Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50-99% stenosis of a 2·25-4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224.

Findings: Between Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63-1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached.

Interpretation: In patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy.

Funding: US Department of Veterans Affairs Cooperative Studies Program.

Conflict of interest statement

Declaration of interests

ESB consults for and receives speaker honoraria from Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, and Nitiloop, and receives research support from Boston Scientific, InfraRedx and Osprey. ESB’s spouse was an employee of Medtronic. DLB is an advisory board member of Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is on the board of directors of Boston VA Research Institute and Society of Cardiovascular Patient Care; is chair of the American Heart Association Quality Oversight Committee; is on the data monitoring committees of Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, and Population Health Research Institute; receives honoraria from the American College of Cardiology, Belvoir Publications, Duke Clinical Research Institute, Harvard Clinical Research Institute, HMP Communications, Journal of the American College of Cardiology, Population Health Research Institute, Slack Publications, Society of Cardiovascular Patient Care, and WebMD; is deputy editor of Clinical Cardiology, and chair of the NCDR-ACTION registry steering committee and VA CART research and publications committee; receives research funding from Abbott, Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi Aventis, and The Medicines Company; receives royalties from Elsevier; is a site co-investigator for Biotronik, Boston Scientific, and St Jude Medical (now Abbott); is a trustee of the American College of Cardiology; and does unfunded research for FlowCo, Merck, PLx Pharma, and Takeda. SG receives research support from the National Institutes of Health, the VA Cooperative Studies Program, the Arizona Biomedical Research Commission, and Merck Pharmaceuticals, and is the co-founder of Avery Therapeutic. SVR consults for Medtronic. KS consults for Medeon Bio Inc, TransAortic Medical, and Terumo, and receives research support from Siemens Medical Systems and Medinol. AAB consults for the American College of Cardiology. SG receives research grants from Edwards Lifesciences and VA Office of Research and Development, and consults for Medtronic, Boston Scientific, Osprey Medical, and Surmodics. FL is a speaker for Abbott Vascular, and consults for Medicure. EA consults for Abbott Vascular, Boston Scientific, Cardiovascular Systems, Medtronic, and Spectranetics. BVR receives a research grant from InfraRedx and the Spectranetics Corporation, and salary support from the VA Cooperative Studies Program. YL consults for PTC Therapeutics and PaxVax. SB receives speaker honoraria from AstraZeneca, CSI, Gore, and Medtronic, and institutional research grants from Boston Scientific Corporation, and Merck. All other authors declare no competing interests.

Copyright © 2018 Elsevier Ltd. All rights reserved.

Figures

Figure 1:. Enrolment, randomisation, and follow-up

The number of patients who were eligible is lower than the number randomly assigned, because some ineligible patients were randomly assigned. SVG=saphenous vein aortocoronary bypass graft. PCI=percutaneous coronary intervention. *Two patients who were screened and randomly assigned without proper consent are not included. †Criteria are not mutually exclusive.

Figure 2:. Clinical outcomes at 12 months

Kaplan-Meier plot of cumulative incidence curves for patients who received drug-eluting stents (DES) or bare-metal stents (BMS) for the primary outcome of target vessel failure (composite outcome of cardiac death, target vessel myocardial infarction, or target vessel revascularisation), cardiac death, target vessel myocardial infarction, and target vessel revascularisation. HR=hazard ratio.