Polymer-free drug-coated coronary stents in diabetic patients at high bleeding risk: a pre-specified sub-study of the LEADERS FREE trial
- 171 Downloads
Diabetics are at increased risk after stent implantation and potentially sensitive to the type of stent and dual anti-platelet therapy (DAPT). The randomized, double-blind LEADERS FREE trial compared 2432 patients at high bleeding risk (HBR) receiving either a polymer-free BA9-coated stent (DCS) or a bare metal stent (BMS) with 1 month of DAPT, and showed superior safety and efficacy of the DCS at 2 years. We report outcomes at 2 years of the pre-specified diabetic subgroup.
Methods and results
The diabetic sub-group comprised 805 (33.1%) patients; 262 (10.8%) were insulin-dependent (IDDM). Compared to non-diabetics, diabetics were younger and had more risk factors and multi-vessel disease. They suffered higher rates of death (15.6 vs. 12.2%, p = 0.01), cardiac death (8.3 vs. 5.9%, p = 0.02), myocardial infarction (MI) (11.1 vs. 7.8%, p = 0.009) and definite/probable stent thrombosis (3.1 vs. 1.7%, p = 0.01), but rates of clinically-indicated TLR (9.1 vs. 9.5%, p = 0.93) and BARC 3–5 bleeding (10.2 vs. 8.4%, p = 0.20) were comparable. Compared to diabetic patients treated with a BMS, diabetic DCS recipients required less clinically driven TLR (6.3 vs. 12.2%, p = 0.006). The primary safety endpoint (cardiac death, MI, definite/probable stent thrombosis) occurred numerically less frequently in the DCS group (14.9 vs. 19.7%, p = 0.10), and was significantly lower in IDDM patients (13.8 vs. 25.4%, p = 0.03). BARC 3–5 was similar for patients treated with DCS (9.9%) and BMS (10.5%, p = 0.84).
In diabetic HBR patients, DCS significantly reduced re-intervention rates over BMS, and showed a strong trend towards a safety benefit at 2 years.
Clinical trial registration
ClinicalTrials.gov number: NCT01623180.
Keywords:Diabetes mellitus Bleeding Drug-coated stents
Compliance with ethical standards
Conflict of interest
M.-C. Morice is the chief executive officer and a shareholder of the Cardiovascular European Research Center (CERC). S. Copt and H.-P. Stoll are full-time employees of the sponsor company (Biosensors). P. Urban is a consultant to Biosensors and has received honoraria from Terumo, Sinomed, Astra-Zeneca, and Edwards Lifesciences during the past 12 months. All other authors have no conflict of interest to disclose.
- 1.Singh M, Gersh BJ, McClelland RL, Ho KK, Willerson JT, Penny WF, Holmes DR Jr (2004) Clinical and angiographic predictors of restenosis after percutaneous coronary intervention: insights from the prevention of restenosis with tranilast and its outcomes (PRESTO) trial. Circulation 109:2727–2731CrossRefGoogle Scholar
- 3.Akin I, Bufe A, Eckardt L, reinecke H, Senges J, Richardt G, Kuck KH, Schneider S, Nienaber CA, DES.DE Study Group (2010) Comparison of outcomes in patients with insulin-dependent versus non-insulin dependent diabetes mellitus receiving drug-eluting stents (from the first phase of the prospective German DES.DE registry). Am J Cardiol 106:1201–1207CrossRefGoogle Scholar
- 5.Kaul U, Bangalore S, Seth A, Arambam P, Abhaichand RK, Patel TM, Banker D, Abhyankar A, Mullasari AS, Shah S, Jain R, Kumar PA, Bahuleyan CG, for the TUXEDO-INDIA Investigators (2015) Paclitaxel-eluting versus Everolimus-eluting coronary stents in diabetes. N Engl J Med 373:1709–1719CrossRefGoogle Scholar
- 6.Urban P, Abizaid A, Chevalier B, Greene S, Meredith IT, Morice MC, Pocock S (2013) Rationale and design of the LEADERS FREE trial: a randomized double-blind comparison of the biofreedom drug-coated stent vs the Gazelle bare metal stent in patients at high bleeding risk using a short (1 month) course of dual antiplatelet therapy. Am Heart Journal 165:704–709CrossRefGoogle Scholar
- 7.Urban P, Meredith IT, Baizaid A, Pocock SJ, Carrie D, Naber C, Lipiecki J, Richartd G, Iniguez A, Brunel P, Valdes-Chavarri M, Garot P, Talwar S, Berland J, Abdellaoui M, Eberli F, Oldroyd K, Zambahari R, Gregson J, Greene S, Stoll HP, Morice MC, for the LEADERS FREE Investigators (2015) Polymer-free drug-coated coronary stents in patients at high bleeding risk. N Engl J Med 373:2038–47CrossRefGoogle Scholar
- 8.Garot P, Morice MC, Tresukosol D, Pocock SJ, Meredith IT, Abizaid A, Carrié D, Naber C, Iñiguez A, Talwar S, Menown IB, Christiansen EH, Gregson J, Copt S, Hovasse T, Lurz P, Maillard L, Krackhardt F, Ong P, Byrne J, Redwood S, Windhövel U, Greene S, Stoll HP, Urban P, for the LEADERS FREE Investigators (2017) 2-Year outcomes of high bleeding risk patients after polymer-free drug-coated stents. J Am Coll Cardiol 69:162–171CrossRefGoogle Scholar
- 9.Koskinas KC, Siontis GC, Piccolo R, Franzone A, Haynes A, Rat-Wirtzler J, Silber S, Serruys PW, Pilgrim T, Räber L, Heg D, Jüni P, Windecker S (2016) Impact of diabetic status on outcomes after revascularization with drug-eluting stents in relation to coronary artery disease complexity: patient-level pooled analysis of 6081 patients. Circ Cardiovasc Interv 9:e003255CrossRefGoogle Scholar
- 10.Farooq V, van Klaveren D, Steyerberg EW, Meliga E, Vergouwe Y, Chieffo A, Kappetein AP, Colombo A, Holmes DR Jr, Mack M, Feldman T, Morice MC, Ståhle E, Onuma Y, Morel MA, Garcia-Garcia HM, van Es GA, Dawkins KD, Mohr FW, Serruys PW (2013) Impact of coronary lesion complexity on drug-eluting stent outcomes in patients with and without diabetes mellitus: analysis from 18 pooled randomized trials. Lancet 381:639–650CrossRefGoogle Scholar
- 11.Tzafiri R, Bailey L, Keating J, Markham P, Dutta D, Kayo M, Edelman E (2017) Sirolimus analog lipophilicity dictates release kinetics and tissue retention after implantation of polymer-free drug coated stents. EuroPCR, Euro17A-POS0527Google Scholar
- 12.Kedhi E, Généreux P, Palmerini T, McAndrew TC, Parise H, Mehran R, Dangas GD, Stone GW (2014) Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention. J Am Coll Cardiol 63:2111–2118CrossRefGoogle Scholar
- 13.Lee SY, Hong MK, Shin DH, Kim JS, Kim BK, Ko YG, Choi D, Jang Y, Kim HS, Valgimigli M, Palmerini T, Stone GW (2017) Clinical outcomes of dual antiplatelet therapy after implantation of drug-eluting stents in patients with different cardiovascular risk factors. Clin Res Cardiol 106:165–173CrossRefGoogle Scholar
- 15.Bønaa KH, Mannsverk J, Wiseth R, Aaberge L, Myreng Y, Nygård O, Nilsen DW, Kløw NE, Uchto M, Trovik T, Bendz B, Stavnes S, Bjørnerheim R, Larsen AI, Slette M, Steigen T, Jakobsen OJ, Bleie Ø, Fossum E, Hanssen TA, Dahl-Eriksen Ø, Njølstad I, Rasmussen K, Wilsgaard T, Nordrehaug JE (2016) Drug-eluting or bare-metal stents for coronary artery disease. N Engl J Med 375:1242–1252CrossRefGoogle Scholar
- 16.Corpus RA, George PB, House JA, Dixon SR, Ajluni SC, Devlin WH, Timmis GC, Balasubramaniam M, O’Neill WW (2004) Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II. J Am Coll Cardiol 43:8–14CrossRefGoogle Scholar