Bern-Rotterdam Registry Published in the Lancet Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study Joost Daemen, MD; Peter Wenaweser, MD; Keiichi Tsuchida, MD; Linda Abrecht, MD; Sophia Vaina, MD; Cyrill Morger, MD; Neville Kukreja, MBBS; Peter Jüni, MD; Georgios Sianos, MD; Gerrit Hellige, MD; Ron T van Domburg, PhD; Otto M Hess, MD; Eric Boersma, PhD; Bernhard Meier, MD; Stephan Windecker, MD; and Patrick W Serruys, MD Published in the Lancet February 24, 2007

Bern-Rotterdam Registry: Background Drug-eluting stents (DES) significantly reduce rates of restenosis and target lesion revascularization compared with bare metal stents (BMS). Since the publication of randomized trials on the two FDA approved DES, sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), these devices have been widely used. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Registry: Background (cont.) However, several safety concerns have since been expressed, including concern about stent thrombosis. Little is known about occurrence of stent thrombosis more than one year after implantation of DES. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Registry: Study Design Registry of 8146 patients undergoing percutaneous coronary intervention (PCI) with PES or SES at two academic hospitals Mean follow-up 3 years Exclusion Criteria: Patients treated with both types of stents (SES and PES) in one lesion, and lesion previously treated with brachytherapy SES n=3823 PES n=4323 3 yrs. follow-up Data assessed to ascertain the incidence, time course, and correlates of stent thrombosis, and the differences between early (0-30 days) and late (>30 days) stent thrombosis and between SES and PES. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Registry: Baseline Characteristics Overall (n= 8146) SES (n=3823) PES (n=4323) p value Age (yrs) 62.6 (11.6) 62.5 (11.5) 62.7 (11.6) 0.31 Male 6065 (75%) 2859 (75%) 3206 (74%) 0.53 Hypertension 3745 (46%) 1965 (51%) 1780 (41%) <.0001 Family History 2279 (28%) 1112 (29%) 1167 (27%) 0.04 Current smoker 2993 (37%) 1721 (45%) 1272 (29%) Dyslipidemia 4079 (50%) 2087 (55%) 1992 (46%) Diabetes 1315 (16%) 697 (18%) 618 (14%) LVEF* 55 (12) 54 (12) 55 (11) 0.01 *Left Ventricular Ejection Fraction Data are recorded as mean (SD) or n (%) Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Registry: Baseline Characteristics Overall (n= 8146) SES (n=3823) PES (n=4323) p value ACS** at presentation 2853/4859 (59%) 795/1481(54%) 2058/3378 (61%) <.0001 Bifurcation treatment 781/4889 (16%) 267/1488 (18%) 514/3401 (15%) 0.01 No. of stents per patient 1.96 (1.23) 1.87 (1.13) 2.03 (1.31) Total stent length per patient (mm) 35.9 (25.3) 33.6 (22.6) 37.9 (27.4) Duration of clopidogrel (mos.) 5.94 (3.1) 4.72 (4.0) 6.36 (2.6) **Acute Coronary Syndrome Data are recorded as mean (SD) or n/total (%) Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Registry: Results Angiographically documented ST occurred in 152 patients. Incidence density was 1.3 per 100 person-years, with a cumulative incidence of 2.9% at three years. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Registry: Results (cont.) Early Stent Thrombosis Late Stent Thrombosis p = 0.031 p = 0.49 Percentage of Patients (%) PES DES PES DES Incidence of early ST was similar for SES and PES, but late ST was more frequent with PES than with SES. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Registry: Results (cont.) Days after PCI 9 30 365 730 1095 Cumulative Incidence of ST (%) 1.1 1.2 1.7 2.3 2.9 Cumulative Events (n) 79 90 116 141 152 Patients at Risk (n) 7173 7041 5549 2852 989 Late stent thrombosis occurred steadily at a constant rate of 0.6% per year up to three years after stent implantation. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Analysis: Results (cont.) At the time of ST, dual antiplatelet therapy was being taken by 87% (early) and 23% (late) of patients, p < 0.0001. Independent predictors of overall ST were acute coronary syndrome at presentation (hazard ratio 2.28, 95% CI 1.29-4.03) and diabetes (HR 2.03, 95% CI 1.07-3.83).

Bern-Rotterdam Analysis: Limitations This was a non-randomized cohort study that was observational in nature, thus possibly disadvantaged by confounding by indication. PES were available for commercial use 1 year later than were SES, and the difference in follow up may have biased results. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Analysis: Limitations (cont.) The data estimate the incidence of stent thrombosis after DES implantation during routine clinical practice at two tertiary care centers, so findings may not apply to institutions with more restricted use of DES. Only angiographically documented cases of stent thrombosis were counted, which might have underrepresented the actual incidence of stent thrombosis. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.

Bern-Rotterdam Analysis: Summary The data suggest that late stent thrombosis occurs at a steady rate during follow-up up to three years, tends to be more frequent with PES than with SES, and can unpredictably occur at any time point despite antiplatelet therapy. Late stent thrombosis complicating the use of DES seems to be a distinct entity with pathophysiological factors that differ from those of early stent thrombosis. Daemen et al. Lancet. 2007 Feb 24; 369: 667 – 78.